Clinical Studies

Abstracts are presented below for clinical studies on Ashwagandha.

  • Botanical Name: Withania Somnifera

  • Ayurvedic Name: Ashwagandha

  • Common Name: Ashwagandha

Withania Somnifera

Plant Phytonutrient Profile


1: Arch Biochem Biophys. 2007 Feb 12; [Epub ahead of print]

Molecular cloning and characterization of one member of 3beta-hydroxy sterol
glucosyltransferase gene family in Withania somnifera.

Sharma LK, Madina BR, Chaturvedi P, Sangwan RS, Tuli R.

National Botanical Research Institute, Rana Pratap Marg, Lucknow 226001, Uttar
Pradesh, India.

Sterol glycosides are constituents of plant cell membranes. Glucosylations of
the sterols are catalyzed by sterol glucosyltransferases (SGTs), which are
members of family 1 glycosyltransferases. We have identified the family of SGT
genes expressed in the leaves of a medicinal plant Withania somnifera. One
member (SGTL1) of this gene family was cloned. The full-length cDNA sequence of
SGTL1 represents 2532 bp, comprising untranslated regions (UTRs) of 337 and 89
bp at the 5' and 3' ends, respectively. The amino acid sequence deduced from the
2103 bp open reading frame (ORF) showed homology (67-45%) to the reported plant
SGTs. The presence of two putative transmembrane domains suggested the
association of SGTL1 with membrane. The SGTL1 was expressed in Escherichia coli
and recombinant enzyme from the supernatant was partially purified and
biochemically characterized. The relative activity and kinetic properties of
SGTL1 for different sterols were compared with a recombinant SGT (GenBank
Accession No. ) of Arabidopsis thaliana (AtSGT). Both the recombinant enzymes
showed activity with 3-beta-OH sterols. The distribution of SGTL1 transcript in
W. somnifera, as determined by quantitative PCR, showed higher expression in
roots and mature leaves. Expression of the SGTL1 transcript in the leaves of W.
somnifera was enhanced following the application of salicylic acid. In contrast,
it decreased rapidly on exposure of the plants to heat shock, suggesting
functional role of the enzyme in biotic and abiotic stresses.

PMID: 17324374 [PubMed - as supplied by publisher]

2: Biochim Biophys Acta. 2007 Jan 8; [Epub ahead of print]

Purification and physico-kinetic characterization of 3beta-hydroxy specific
sterol glucosyltransferase from Withania somnifera (L) and its stress response.

Madina BR, Sharma LK, Chaturvedi P, Sangwan RS, Tuli R.

National Botanical Research Institute, Rana Pratap Marg, Lucknow-226001, (U.P.)
India.

Sterol glycosyltransferases catalyze the synthesis of diverse glycosteroids in
plants, leading to a change in their participation in cellular metabolism.
Withania somnifera is a medically important plant, known for a variety of
pharmacologically important withanolides and their glycosides. In this study, a
cytosolic sterol glucosyltransferase was purified 3406 fold to near homogeneity
from W. somnifera leaves and studied for its biochemical and kinetic properties.
The purified enzyme was active with UDP-glucose but not with UDP-galactose as
sugar donor. It exhibited broad sterol specificity by glucosylating a variety of
sterols and phytosterols with 3beta-OH group. It showed a low level of activity
with flavonoids and isoflavonoids. The enzyme gave maximum K(cat)/K(m) value
(0.957) for 24-methylenecholesterol that resembles aglycone structure of
pharmacologically important sitoindosides VII and VIII from W. somnifera. The
enzyme follows ordered sequential bisubstrate mechanism of reaction, in which
UDP-glucose and sterol are the first and second binding substrates. This is the
first detailed kinetic study on purified plant cytosolic sterol
glucosyltransferases. Results on peptide mass fingerprinting and substrate
specificity suggested that the enzyme belongs to the family of secondary
metabolite glucosylating glucosyltransferases. The enzyme activity exhibited a
rapid in vivo response to high temperature and salicylic acid treatment of
plants, suggesting its physiological role in abiotic and biotic stress.

PMID: 17293176 [PubMed - as supplied by publisher]

3: Phytother Res. 2007 Jan 12; [Epub ahead of print]

In Vivo antimalarial activity of aqueous extracts from Kenyan medicinal plants
and their Chloroquine (CQ) potentiation effects against a blood-induced
CQ-resistant rodent parasite in mice.

Muregi FW, Ishih A, Suzuki T, Kino H, Amano T, Mkoji GM, Miyase T, Terada M.

Department of Parasitology, Hamamatsu University School of Medicine, 1-20-1
Handayama, Hamamatsu 431-3192, Japan.

Hot water extracts from eight medicinal plants representing five families, used
for malaria treatment in Kenya were screened for their in vivo antimalarial
activity in mice against a chloroquine (CQ) resistant Plasmodium berghei NK65,
either alone or in combination with CQ. Extracts of three plants, Toddalia
asiatica (root bark), Rhamnus prinoides (leaves and root bark) and Vernonia
lasiopus (root bark) showed high chemosuppression in the range 51%-75%. Maytenus
acuminata, M. heterophylla, M. senegalensis and Rhamnus staddo had moderate
activities of 33%-49% parasitaemia suppression in the root bark and/or leaf
extracts, while Withania somnifera (root bark) had a non-significant suppression
(21%). In combination with CQ, extracts of V. lasiopus (all parts), leaf
extracts of M. senegalensis, R. prinoides and T. asiatica as well as root barks
of M. heterophylla, R. staddo and T. asiatica had improved parasitaemia
suppression in the range 38%-66%, indicating synergistic interactions.
Remarkable parasitaemia suppression by the extracts, either alone or in
combination with CQ resulted into longer survival of mice relative to the
controls, in some cases by more than 2 weeks. Plants, which showed significant
antimalarial activity including V. lasiopus, T. asiatica and R. prinoides,
should further be evaluated in the search for novel agents against
drug-resistant malaria. Copyright (c) 2007 John Wiley & Sons, Ltd.

PMID: 17221829 [PubMed - as supplied by publisher]

4: Chem Biodivers. 2004 Sep;1(9):1289-95.

Cholinesterase-inhibiting withanolides from Ajuga bracteosa.

Riaz N, Malik A; Aziz-ur-Rehman; Nawaz SA, Muhammad P, Choudhary MI.

International Centre for Chemical Sciences, H.E.J. Research Institute of
Chemistry, University of Karachi, Karachi-75270, Pakistan.

Three new withanolides, bracteosin A (= (22R)-5beta,6beta :
22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxyergost-24-ene-1,26-dione; 1),
bracteosin B (= (22R)-5beta,6beta :
22,26-diepoxy-4beta,28-dihydroxy-3beta-methoxy-1,26-dioxoergost-24-en-19-oic
acid; 2), and bracteosin C (=
(22R)-22,26-epoxy-4beta,6beta,27-trihydroxy-3beta-methoxyergost-24-ene-1,26-dion
e; 3), have been isolated from the whole plants of Ajuga bracteosa. Their
structures were deduced by spectral analysis, including 1D- and 2D-NMR
techniques. In addition, dihydroclerodin-1, clerodinin A, lupulin A, and
dihydroajugapitin have also been isolated for the first time from this species.
Compounds 1-3 exhibited evident inhibitory potential against cholinesterase
enzymes in a concentration-dependent fashion.

PMID: 17191906 [PubMed - indexed for MEDLINE]

5: J Nat Prod. 2006 Dec;69(12):1790-2.

Ashwagandhanolide, a bioactive dimeric thiowithanolide isolated from the roots
of Withania somnifera.

Subbaraju GV, Vanisree M, Rao CV, Sivaramakrishna C, Sridhar P, Jayaprakasam B,
Nair MG.

Laila Research Center, Unit I, Phase III, Jawahar Autonagar, Vijayawada 520 007,
India. [email protected]

A new dimeric withanolide, ashwagandhanolide (1), was isolated from the roots of
an Ayurvedic medicinal herb, Withania somnifera. A detailed spectroscopic
evaluation revealed its identity as a dimer with an unusual thioether linkage.
Compound 1 displayed growth inhibition against human gastric (AGS), breast
(MCF-7), central nervous system (SF-268), colon (HCT-116), and lung (NCI H460)
cancer cell lines, with IC50 values in the range 0.43-1.48 microg/mL. In
addition, it inhibited lipid peroxidation and the activity of the enzyme
cyclooxygenase-2 in vitro.

PMID: 17190461 [PubMed - indexed for MEDLINE]

6: Cancer Res. 2007 Jan 1;67(1):246-53. Epub 2006 Dec 21.

Par-4-dependent apoptosis by the dietary compound withaferin A in prostate
cancer cells.

Srinivasan S, Ranga RS, Burikhanov R, Han SS, Chendil D.

Department of Clinical Sciences, College of Health Sciences, University of
Kentucky, 900 South Limestone Street, Lexington, KY 40536, USA.

Deletion or mutation of the androgen receptor (AR) renders prostate tumors
refractory to apoptosis by androgen ablation, the mainstay of prostate cancer
therapy. To identify novel therapeutics that can induce apoptosis regardless of
the AR status of prostate cancer cells, we screened dietary herbal compounds
using a reporter assay for the prostate apoptosis response-4 (Par-4) gene, which
induces p53- and PTEN-independent and cancer-selective apoptosis. One of the
compounds, withaferin A (WA), a major constituent of the dietary compound
Withania somnifera, induced Par-4-dependent apoptosis in androgen-refractory
prostate cancer cells and regression of PC-3 xenografts in nude mice.
Interestingly, restoration of wild-type AR in PC-3 (AR negative) cells abrogated
both Par-4 induction and apoptosis by WA. Individually, WA and anti-androgens
induced neither Par-4 nor apoptosis in androgen-responsive prostate cancer
cells, yet in combination, WA and anti-androgen synergistically induced Par-4
and apoptosis in androgen-responsive prostate cancer cells. Thus, when
judiciously combined with anti-androgens, WA inhibits survival of both
androgen-responsive and androgen-refractory prostate cancer cells by a
Par-4-dependent mechanism. As Par-4 up-regulation induces apoptosis in most
tumor cells, our findings can be extended to high-throughput screens to identify
synergistic combinations for both therapy-sensitive and therapy-resistant
cancers.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17185378 [PubMed - indexed for MEDLINE]

7: Altern Med Rev. 2006 Dec;11(4):269-77.

Ancient medicine, modern use: Withania somnifera and its potential role in
integrative oncology.

Winters M.

Withania somnifera Dunal, commonly known as ashwagandha, has been used for
centuries in Ayurvedic medicine to increase longevity and vitality. Western
research supports its polypharmaceutical use, confirming antioxidant,
anti-inflammatory, immune-modulating, and antistress properties in the whole
plant extract and several separate constituents. This article reviews the
literature pertaining to Withania somnifera and its botanical constituents as
antitumor agents and in conjunction with radiation and chemotherapy treatment.
Following a search of MEDLINE and EBSCO databases, it can be concluded that
Withania somnifera reduces tumor cell proliferation while increasing overall
animal survival time. Furthermore, it has been shown to enhance the
effectiveness of radiation therapy while potentially mitigating undesirable side
effects. Withania somnifera also reduces the side effects of chemotherapeutic
agents cyclophosphamide and paclitaxel without interfering with the
tumor-reducing actions of the drugs. These effects have been demonstrated in
vitro on human cancer cell lines, and in vivo on animal subjects, but there have
been no human trials to date. Given its broad spectrum of cytotoxic and
tumor-sensitizing actions, Withania somnifera presents itself as a novel
complementary therapy for integrative oncology care.

Publication Types:
Review

PMID: 17176166 [PubMed - indexed for MEDLINE]

8: J Biol Chem. 2007 Feb 16;282(7):4253-4264. Epub 2006 Dec 6.

Withaferin A Strongly Elicits I{kappa}B Kinase beta Hyperphosphorylation
Concomitant with Potent Inhibition of Its Kinase Activity.

Kaileh M, Vanden Berghe W, Heyerick A, Horion J, Piette J, Libert C, De
Keukeleire D, Essawi T, Haegeman G.

Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST),
Department of Molecular Biology, Ghent University-UGent, K. L. Ledeganckstraat
35, B-9000 Gent, Belgium, Master program in Clinical Laboratory Sciences,
Birzeit University, P. O. Box 14, Birzeit, Palestine, Center for Biomedical
Integrated Genoproteomics (CBIG), Virology and Immunology Unit, Institute of
Pathology B23, B-4000 Liege, Belgium, Department of Molecular Biomedical
Research, Flanders Interuniversity for Biotechnology and Ghent University,
Technologiepark 927, B-9052 Zwijnaarde, Belgium, and Laboratory of Pharmacognosy
and Phytochemistry, Ghent University-UGent, Harelbekestraat 72, B-9000 Gent,
Belgium.

The transcription factor NFkappaB plays a critical role in normal and
pathophysiological immune responses. Therefore, NFkappaB and the signaling
pathways that regulate its activation have become a major focus of drug
development programs. Withania somnifera (WS) is a medicinal plant that is
widely used in Palestine for the treatment of various inflammatory disorders. In
this study we show that the leave extract of WS, as well as its major
constituent withaferin A (WA), potently inhibits NFkappaB activation by
preventing the tumor necrosis factor-induced activation of IkappaB kinase beta
via a thioalkylation-sensitive redox mechanism, whereas other WS-derived
steroidal lactones, such as withanolide A and 12-deoxywithastramonolide, are far
less effective. To our knowledge, this is the first communication of IkappaB
kinase beta inhibition by a plant-derived inhibitor, coinciding with
MEK1/ERK-dependent Ser-181 hyperphosphorylation. This prevents IkappaB
phosphorylation and degradation, which subsequently blocks NFkappaB
translocation, NFkappaB/DNA binding, and gene transcription. Taken together, our
results indicate that pure WA or WA-enriched WS extracts can be considered as a
novel class of NFkappaB inhibitors, which hold promise as novel
anti-inflammatory agents for treatment of various inflammatory disorders and/or
cancer.

PMID: 17150968 [PubMed - as supplied by publisher]

9: J Ethnopharmacol. 2006 Nov 15; [Epub ahead of print]

Antimalarial activity of methanolic extracts from plants used in Kenyan
ethnomedicine and their interactions with chloroquine (CQ) against a CQ-tolerant
rodent parasite, in mice.

Muregi FW, Ishih A, Miyase T, Suzuki T, Kino H, Amano T, Mkoji GM, Terada M.

Department of Parasitology, Hamamatsu University School of Medicine, 1-20-1
Handayama, Hamamatsu 431-3192, Japan; Centre for Biotechnology Research and
Development, Kenya Medical Research Institute (KEMRI), P.O. Box 54840-00200,
Nairobi, Kenya.

Methanolic extracts from 15 medicinal plants representing 11 families, used
traditionally for malaria treatment in Kenya were screened for their in vivo
antimalarial activity in mice against a chloroquine (CQ)-tolerant Plasmodium
berghei NK65, either alone or in combination with CQ. The plant parts used
ranged from leaves (L), stem bark (SB), root bark (RB), seeds (S) and whole
plant (W). When used alone, extracts from seven plants, Clerodendrum myricoides
(RB), Ficus sur (L/SB/RB), Maytenus acuminata (L/RB), Rhamnus prinoides (L/RB),
Rhamnus staddo (RB), Toddalia asiatica (RB) and Vernonia lasiopus (RB) had
statistically significant parasitaemia suppressions of 31.7-59.3%. In
combination with CQ, methanolic extracts of Albizia gummifera (SB), Ficus sur
(RB), Rhamnus prinoides and Rhamnus staddo (L/RB), Caesalpinia volkensii (L),
Maytenus senegalensis (L/RB), Withania somnifera (RB), Ekebergia capensis
(L/SB), Toddalia asiatica (L/RB) and Vernonia lasiopus (L/SB/RB) gave
statistically significant and improved suppressions which ranged from 45.5 to
85.1%. The fact that these activities were up to five-fold higher than that of
extract alone may suggest synergistic interactions. Remarkable parasitaemia
suppression by the extracts, either alone or in combination with CQ mostly
resulted into longer mouse survival relative to the controls, in some cases by a
further 2 weeks. Plants, which showed significant antimalarial activity
including Vernonia lasiopus, Toddalia asiatica, Ficus sur, Rhamnus prinoides and
Rhamnus staddo warrant further evaluation in the search for novel antimalarial
agents against drug-resistant malaria.

PMID: 17145149 [PubMed - as supplied by publisher]

10: Plant Cell Rep. 2006 Nov 15; [Epub ahead of print]

Changes in morphological phenotypes and withanolide composition of
Ri-transformed roots of Withania somnifera.

Bandyopadhyay M, Jha S, Tepfer D.

Centre of Advanced Study in Cell and Chromosome Research, Department of Botany,
University of Calcutta, 35 Ballygunge Circular Road, Calcutta, 700019, India,
[email protected]

Developmental variability was introduced into Withania somnifera using genetic
transformation by Agrobacterium rhizogenes, with the aim of changing
withasteroid production. Inoculation of W. somnifera with A. rhizogenes strains
LBA 9402 and A4 produced typical transformed root lines, transformed callus
lines, and rooty callus lines with simultaneous root dedifferentiation and
redifferentiation. These morphologically distinct transformed lines varied in
T-DNA content, growth rates, and withasteroid accumulation. All of the lines
with the typical transformed root morphology contained the T(L) T-DNA, and 90%
of them carried the T(R) T-DNA, irrespective of the strain used for infection.
Accumulation of withaferin A was maximum (0.44% dry weight) in the transformed
root line WSKHRL-1. This is the first detection of withaferin A in the roots of
W. somnifera. All of the rooty callus lines induced by strain A4 contained both
the T(L) and the T(R)-DNAs. In contrast, 50% of the rooty-callus lines obtained
with strain LBA 9402 contained only the T(R) T-DNA. All the rooty callus lines
accumulated both withaferin A and withanolide D. The callusing lines induced by
LBA 9402 lacked the T(L) T-DNA genes, while all the callusing lines induced by
strain A4 contained the T(L) DNA. Four of these callus lines produced both
withaferin A (0.15-0.21% dry weight) and withanolide D (0.08-0.11% dry weight),
and they grew faster than the transformed root lines. This is the first report
of the presence of withasteroids in undifferentiated callus cultures of W.
somnifera.

PMID: 17103214 [PubMed - as supplied by publisher]

11: Chem Biol Interact. 2006 Dec 15;164(3):174-80. Epub 2006 Nov 7.

Suppressive effect of Withania somnifera root powder on experimental gouty
arthritis: An in vivo and in vitro study.

Rasool M, Varalakshmi P.

Faculty of Biosciences, School of Bioengineering and Biosciences, Vellore
Institute of Technology (Deemed University), Vellore 632014, Tamil Nadu, India.
[email protected]

The effect of Withania somnifera L. Dunal root powder on paw volume and serum
lysosomal enzyme activities was investigated in monosodium urate crystal-induced
rats. The levels of beta-glucuronidase and lactate dehydrogenase were also
measured in monosodium urate crystal incubated polymorphonuclear leucocytes
(PMNL). A significant increase in the level of paw volume and serum lysosomal
enzymes was observed in monosodium urate crystal-induced rats. The increased
beta-glucuronidase and lactate dehydrogenase level were observed in untreated
monosodium urate crystal incubated polymorphonuclear leucocytes. On treatment
with the W. somnifera root powder (500/1000 mg/kg body weight), the above
changes were reverted back to near normal levels. W. somnifera also showed
potent analgesic and antipyretic effect with the absence of gastric damage at
different dose levels in experimental rats. For comparison purpose,
non-steroidal anti-inflammatory drug (NSAID) indomethacin was used as a
standard. These results provide evidence for the suppressive effect of W.
somnifera root powder by retarding amplification and propagation of the
inflammatory response without causing any gastric damage.

PMID: 17084827 [PubMed - indexed for MEDLINE]

12: J Clin Rheumatol. 2004 Oct;10(5):236-245.

A 32-Week Randomized, Placebo-Controlled Clinical Evaluation of RA-11, an
Ayurvedic Drug, on Osteoarthritis of the Knees.

Chopra A, Lavin P, Patwardhan B, Chitre D.

From the *Center for Rheumatic Diseases, Inlaks and Budhrani Hospital, Bharati
Hospital Medical College (Deemed University), Pune, India; daggerAverion, Inc.,
Framingham, Massachusetts; the double daggerSchool of Health Sciences,
University of Pune, India; and section signBIO-VED Pharmaceuticals, Inc., San
Jose, California.

BACKGROUND:: The ancient Indian (Asian) Ayurvedic medicinal system uses
herbomineral drugs to treat arthritis. Despite centuries of use, very few have
been tested by drug trials. RA-11 (ARTREX, MENDAR), a standardized multiplant
Ayurvedic drug (Withania somnifera, Boswellia serrata, Zingiber officinale, and
Curcuma longa) is currently used to treat arthritis. OBJECTIVE:: The objective
of this study was to evaluate the efficacy and safety of RA-11 in patients with
symptomatic osteoarthritis (OA) of the knees. METHODS:: A total of 358 patients
with chronic knee pain were screened free-of-cost in "arthritis camps" in an
Indian metropolis. Ninety patients with primary OA of the knees (ACR
classification; Arthritis Rheum 1986;29:1039-1049) were found eligible
(postanalgesic washout pain visual analog score [VAS] >/=40 mm in either or both
knees on body weight-bearing activities) to enroll into a randomized,
double-blind, placebo-controlled, parallel efficacy, single-center, 32-week drug
trial (80% power to detect 25% difference, P = 0.05, 2-sided). Concurrent
analgesics/nonsteroidal antiinflammatory drugs and steroids in any form were not
allowed. Lifestyle and/or dietary restrictions, as per routine Ayurveda
practices, were not imposed. Pain VAS (maximum pain in each knee recorded by the
patient during the preceding 48 hours) and modified WOMAC (Western Ontario
McMaster University OA Index, Likert scale, version 3.0) were the primary
efficacy variables. The WOMAC section on "physical function difficulty" was
modified for Indian use and validated before the trial. Routine laboratory
testing was primarily done to monitor drug safety. At baseline, the groups
(active = 45, placebo = 45) were well matched for several measures (mean pain
VAS: active = 6.17; placebo = 6.5). RESULTS:: 1) Efficacy: Compared with
placebo, the mean reduction in pain VAS at week 16 (active = 2.7, placebo = 1.3)
and week 32 (active = 2.8, placebo = 1.8) in the active group was significantly
(P <0.05, analysis of variance [ANOVA]) better. Similarly, the improvement in
the WOMAC scores at week 16 and week 32 were also significantly superior (P
<0.01, ANOVA) in the active group. 2) Safety: Both the groups reported mild
adverse events (AE) without any significant difference. 3) Withdrawals:
Twenty-eight patients were discontinued. None reported drug-related toxicity.
The majority failed follow up/compliance. No differences were observed between
the groups. CONCLUSION:: This controlled drug trial demonstrates the potential
efficacy and safety of RA- 11 in the symptomatic treatment of OA knees over 32
weeks of therapy.

PMID: 17043520 [PubMed - as supplied by publisher]

13: Ann Transplant. 2005;10(4):6-10.

The new approaches to preservation of graft cell integrity in preservation for
transplantation.

Gewartowska M, Olszewski WL.

Department of Surgical Research and Transplantology, Medical Research Center,
Polish Academy of Sciences, Warsaw, Poland.

Restoration of cell plasma membrane integrity after injury is essential for the
survival of animal cells. In case of graft preservation or during chemotherapy
in cancer, cell membrane integrity and the process of its repair are disrupted.
Cytoprotective substances are important in such cases, as well as in other
diseases, for example in myocardial infarction, acute insults and in chronic
neurodegenerative diseases. Hyperosmolarity is a condition in which cell
membrane stability may be damaged in vivo but preserved in the in vitro
conditions. Hypertonicity causes water leaving from cells by osmosis, decreasing
cell volume and increasing of intracellular ionic strength. High intracellular
ionic strength perturbs cellular function by decreasing the rates of biochemical
reaction. We review the new experimentally studied cytoprotective substances and
their application in cell membrane protection. Moreover, we present our data on
the effects of hyperosmolarity and its protective effect on cell internal
structure.

Publication Types:
Review

PMID: 17037081 [PubMed - indexed for MEDLINE]

14: Lett Appl Microbiol. 2006 Nov;43(5):469-74.

Inhibition of aflatoxin B production of Aspergillus flavus, isolated from
soybean seeds by certain natural plant products.

Krishnamurthy YL, Shashikala J.

Department of P.G. Studies and Research in Applied Botany, Kuvempu University,
Shankaraghatta, Shimoga District, Karnataka, India. [email protected]

AIMS: The inhibitory effect of cowdung fumes, Captan, leaf powder of Withania
somnifera, Hyptis suaveolens, Eucalyptus citriodora, peel powder of Citrus
sinensis, Citrus medica and Punica granatum, neem cake and pongamia cake and
spore suspension of Trichoderma harzianum and Aspergillus niger on aflatoxin
B(1) production by toxigenic strain of Aspergillus flavus isolated from soybean
seeds was investigated. METHODS AND RESULTS: Soybean seed was treated with
different natural products and fungicide captan and was inoculated with
toxigenic strain of A. flavus and incubated for different periods. The results
showed that all the treatments were effective in controlling aflatoxin B(1)
production. Captan, neem cake, spore suspension of T. harzianum, A. niger and
combination of both reduced the level of aflatoxin B(1) to a great extent. Leaf
powder of W. somnifera, H. suaveolens, peel powder of C. sinensis, C. medica and
pongamia cake also controlled the aflatoxin B(1) production. CONCLUSIONS: All
the natural product treatments applied were significantly effective in
inhibiting aflatoxin B(1) production on soybean seeds by A. flavus. SIGNIFICANCE
AND IMPACT OF THE STUDY: These natural plant products may successfully replace
chemical fungicides and provide an alternative method to protect soybean and
other agricultural commodities from aflatoxin B(1) production by A. flavus.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17032218 [PubMed - indexed for MEDLINE]

15: Int J Oncol. 2006 Nov;29(5):1269-78.

Chemopreventative strategies targeting the MGMT repair protein: augmented
expression in human lymphocytes and tumor cells by ethanolic and aqueous
extracts of several Indian medicinal plants.

Niture SK, Rao US, Srivenugopal KS.

Center for Cancer Biology, Department of Pharmaceutical Sciences, Texas Tech
University Health Sciences Center, Amarillo, TX 79106, USA.

O6-alkylguanines are potent mutagenic, pro-carcinogenic and cytotoxic lesions
induced by exogenous and endogenous alkylating agents. A facilitated elimination
of these lesions by increasing the activity of O6-methylguanine-DNA
methyltransferase (MGMT) is likely to be a beneficial chemoprevention strategy,
which, however, has not been examined. Because, a marginal enhancement of this
protein may be adequate for genomic protection, we studied alterations in MGMT
activity and expression in human peripheral blood lymphocytes and cancer cell
lines induced by water-soluble and alcohol-soluble constituents of several
plants with established antioxidant and medicinal properties. Both the ethanolic
and aqueous extracts from neem (Azadirachta indica), holy basil (Ocimum
sanctum), winter cherry (Withania somnifera), and oregano (Origanum majorana)
increased the levels of MGMT protein and its demethylation activity in a
time-dependent manner with a maximum of 3-fold increase after 72-h treatment.
The extracts from gooseberry (Emblica officinalis), common basil (Ocimum
basilicum), and spearmint (Mentha viridis) were relatively less efficient in
raising MGMT levels. Increased levels of MGMT mRNA accounted at least, in part,
for the increased activity of the DNA repair protein. The herbal treatments also
increased glutathione S-transferase-pi (GSTP1) expression, albeit to a lesser
extent than MGMT. These data provide the first evidence for the upregulation of
human MGMT by plant constituents and raise the possibility of rational dietary
approaches for attenuating alkylation-induced carcinogenesis. Further, they
reveal the putative antioxidant responsiveness of the MGMT gene in human cells.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

PMID: 17016661 [PubMed - indexed for MEDLINE]

16: Biofactors. 2006;27(1-4):53-67.

Enhanced cardiovascular function and energy level by a novel chromium
(III)-supplement.

Thirunavukkarasu M, Penumathsa S, Juhasz B, Zhan L, Bagchi M, Yasmin T, Shara
MA, Thatte HS, Bagchi D, Maulik N.

Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery,
University of Connecticut Medical Center, 263 Farmington Avenue, Farmington, CT
06030, USA.

The impetus for the novel Energy Formula (EF) which combines the niacin-bound
chromium (III) (0.45%) (NBC), standardized extract of Withania somnifera
extracts (10.71%), caffeine (22.76%), D-ribose (10.71%) and selected amino acids
such as phenylalanine, taurine and glutamine (55.37%) was based on the knowledge
of the cardioprotective potentials of the Withania somnifera extract, caffeine
and D-ribose as well as their abilities to increase energy levels and the
abilities of amino acids to increase the muscle mass and energy levels. The
effect of oral supplementation of EF on the safety, myocardial energy levels and
cardioprotective ability were investigated in an ischemic-reperfused myocardium
model in both male and female Sprague-Dawley rats over 90 days trial period. At
the completion of 90 days, the EF-treated male and female rats gained 9.4% and
3.1% less body weights, respectively, as compared to their corresponding control
groups. No significant difference was found in the levels of lipid peroxidation
and activities of hepatic Aspartate transaminase, Alanine transaminase and
Alkaline phosphatase in EF treatment when compared with control animals. The
male and female rat hearts were subjected to 30 min of global ischemia followed
by 2 h of reperfusion at 30 and 90 days of EF treatment. Cardiovascular
functions including heart rate, coronary flow, aortic flow, dp/dt(max), left
ventricular developed pressure (LVDP) and infarct size were monitored. The
levels of myocardial adenosine triphosphate (ATP), creatine phosphate (CP),
phospho-adenosine monophosphate kinase (p-AMPK) levels, were analyzed at the end
of 30 and 90 days of treatment. Significant improvement was observed in all
parameters in the EF treatment groups as compared to their corresponding
controls. Thus the niacin-bound chromium (III) based energy formula is safe and
effective supplement to boost energy levels and cardioprotection.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17012764 [PubMed - in process]

17: J Basic Microbiol. 2006;46(5):365-74.

Antimicrobial properties of a non-toxic glycoprotein (WSG) from Withania
somnifera (Ashwagandha).

Girish KS, Machiah KD, Ushanandini S, Harish Kumar K, Nagaraju S, Govindappa M,
Vedavathi M, Kemparaju K.

Department of Biochemistry, University of Mysore, Manasagangothri, Mysore-560
006, India.

A monomeric glycoprotein with a molecular mass of 28 kDa in SDS-PAGE was
isolated from the Withania somnifera root tubers. The protein designated WSG
(Withania somnifera glycoprotein) demonstrated potent antimicrobial activity
against the phytopathogenic fungi and bacteria tested. Antifungal effect has
been demonstrated in that WSG exerts a fungistastic effect by inhibiting spore
germination and hyphal growth in the tested fungi. WSG showed potent antifungal
activity against Aspergillus flavus, Fusarium oxysporum, F. verticilloides and
antibacterial activity against Clvibacter michiganensis subsp. michiganensis.
WSG is an acidic, non-toxic (trypsin-chymotrypsin) protease inhibitor. These
results encourage further studies of WSG as a potential therapeutic agent for
its antifungal activity.

PMID: 17009292 [PubMed - indexed for MEDLINE]

18: Mol Cell Biochem. 2006 Nov;292(1-2):13-7. Epub 2006 Sep 27.

Stabilization of membrane bound enzyme profiles and lipid peroxidation by
Withania somnifera along with paclitaxel on benzo(a)pyrene induced experimental
lung cancer.

Senthilnathan P, Padmavathi R, Magesh V, Sakthisekaran D.

Department of Medical Biochemistry, Dr. ALM Postgraduate Institute of Basic
Medical Sciences, University of Madras, Taramani, Chennai 600113, India.

The present study was aimed to evaluate the therapeutic effects of Withania
somnifera along with paclitaxel on lung tumor induced by benzo(a)pyrene in male
Swiss albino mice. The levels of ATPase enzymes and lipid peroxidation were
evaluated in lung cancer bearing mice, in erythrocyte membrane and tissues. The
extent of peroxidation was estimated by measuring the thiobarbituric
acid-reactive substances. Simultaneously the activities of different ATPases
(Na(+)/K(+)-ATPases, Mg(2+)-ATPases and Ca(2+)-ATPases) were determined. The
alterations of these enzyme activities in membrane and tissues were indicative
of the tumor formation caused by benzo(a)pyrene (50 mg/kg body weight, orally)
in cancer bearing animals. The activities of these enzymes were reversed to near
normal control values in animals treated with Withania somnifera (400 mg/kg
b.wt, orally) along with paclitaxel (33 mg/kg b.wt, i.p). Treatment with
Withania somnifera along with paclitaxel altered these damage mediated through
free radicals, and the treatment displays the protective role of these drugs by
inhibiting free radical mediated cellular damages. Over, based on the data
providing a correlation Withania somnifera along with paclitaxel provide
stabilization of membrane bound enzyme profiles and decreased lipid peroxidation
against benzo(a)pyrene induced lung cancer in mice.

PMID: 17003952 [PubMed - indexed for MEDLINE]

19: Phytochemistry. 2006 Oct;67(20):2269-76. Epub 2006 Sep 7.

Phytochemical and genetic analysis in selected chemotypes of Withania somnifera.

Dhar RS, Verma V, Suri KA, Sangwan RS, Satti NK, Kumar A, Tuli R, Qazi GN.

Regional Research Laboratory, RRL, Biotechnology Division, Canal Road, Jammu,
Tawi 180001, India.

The main active components and genetic profile of 15 selected accessions of
Withania somnifera Dunal. were analysed. Ethanolic extract of the dried
roots/leaves of the plant was concentrated under pressure at 50+/-5 degrees C
and was analysed for main compounds (withanolides and withaferin A) by HPLC. All
the main components were found to be present in accessions (AGB 002, AGB 009,
RSS 009, RSS 033). Correlation of these main components with their genetic
factors, was undertaken using AFLP (amplified fragment length polymorphism)
markers. Among 64 primers 7 yielded optimum polymorphism. A total of 913
polymorphic peaks were generated using these primers. Jaccard's similarity
coefficient indicated that accessions having almost the same active compounds
clustered together. The present study demonstrates that AFLP can be successfully
used to resolve the correlation of AFLP data with the presence of secondary
metabolites.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16956635 [PubMed - indexed for MEDLINE]

20: J Ethnopharmacol. 2007 Jan 19;109(2):359-63. Epub 2006 Aug 4.

Screening of selected Indian medicinal plants for acetylcholinesterase
inhibitory activity.

Vinutha B, Prashanth D, Salma K, Sreeja SL, Pratiti D, Padmaja R, Radhika S,
Amit A, Venkateshwarlu K, Deepak M.

Department of Pharmacognosy, Al-Ameen College of Pharmacy, Hosur Road,
Bangalore, India.

Seventy-six plant extracts including methanolic and successive water extracts
from 37 Indian medicinal plants were investigated for acetylcholinesterase
(AChE) inhibitory activity (in vitro). Results indicated that methanolic
extracts to be more active than water extracts. The potent AChE inhibiting
methanolic plant extracts included Withania somnifera (root), Semecarpus
anacardium (stem bark), Embelia ribes (Root), Tinospora cordifolia (stem), Ficus
religiosa (stem bark) and Nardostachys jatamansi (rhizome). The IC(50) values
obtained for these extracts were 33.38, 16.74, 23.04, 38.36, 73.69 and
47.21mug/ml, respectively. These results partly substantiate the traditional use
of these herbs for improvement of cognition.

PMID: 16950584 [PubMed - in process]

21: Invest Ophthalmol Vis Sci. 2006 Sep;47(9):4138-45.

Small molecule anti-angiogenic probes of the ubiquitin proteasome pathway:
potential application to choroidal neovascularization.

Bargagna-Mohan P, Ravindranath PP, Mohan R.

Department of Ophthalmology and Visual Sciences, University of Kentucky,
Lexington, KY 40536, USA.

PURPOSE: To characterize the angiogenic and inflammatory responses of human
choroidal endothelial cells (HCECs) to stimulators and inhibitors of the
ubiquitin proteasome pathway (UPP). METHODS: The regulation of the UPP by the
inhibitor withaferin A and its congener, withanolide D, two natural products
derived from the medicinal plant Withania somnifera was assessed in the
three-dimensional endothelial cell sprouting assay (3D-ECSA), by using HCEC- and
human umbilical vein endothelial cell (HUVEC)-derived spheroids embedded in a
collagen I matrix. Western blot analysis was used to investigate the effect of
withanolides on IkappaB-alpha, polyubiquitination, and heme oxygenase (HO)-1
regulation in HCEC and HUVEC cultures. RESULTS: HCECs, like HUVECs, responded to
fibroblast growth factor-2, vascular endothelial growth factor, and tumor
necrosis factor (TNF)-alpha stimulation and sprouted vessel-like structures in
collagen I matrix. However, HCECs were slower to generate these sprouting
vessels, when compared with HUVECs. The extent of inhibition of endothelial cell
sprouting in 3D matrix, the blockade of TNF-alpha-induced IkappaB-alpha
degradation, levels of global polyubiquitinated proteins, and induced production
of HO-1 in response to treatment by the withanolides in cultured endothelial
cells was similarly regulated between HCECs and HUVECs. CONCLUSIONS: HCECs share
with HUVECs a similar response to UPP inhibitors, suggesting that this
well-conserved pathway that regulates angioinflammatory mechanisms could be
exploited for drug-targeting in the development of novel agents for CNV
treatment.

PMID: 16936134 [PubMed - indexed for MEDLINE]

22: Int Immunopharmacol. 2006 Oct;6(10):1535-42. Epub 2006 Apr 27.

Prophylactic administration of Withania somnifera extract increases host
resistance in Listeria monocytogenes infected mice.

Teixeira ST, Valadares MC, Goncalves SA, de Melo A, Queiroz ML.

Fisiopatologia Medica, Faculdade de Ciencias Medicas, FCM, Universidade Estadual
de Campinas, UNICAMP, Campinas, SP, Brazil.

In this study, we demonstrated that Withania somnifera L. extract (WSE) protects
mice from a lethal dose of Listeria monocytogenes when administered
prophylactically at 100, 250 and 500 mg/kg for 10 days, with survival rates up
to 30%. These doses also prevented the myelosuppression and the splenomegaly
caused by a sublethal infection with L. monocytogenes, due to increased numbers
of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow. Investigation
of the production of colony-stimulating factors (CSFs) revealed increased
colony-stimulating activity (CSA) in the serum of normal and infected mice
pre-treated with WSE. Further studies to investigate the levels of
interferon-gamma (INF-gamma) and lymphocyte cell proliferation were undertaken.
We observed dose-dependent increases in cell proliferation and in the levels of
INF-gamma in mice infected with L. monocytogenes and treated with WSE. All
together, our results suggest that WSE indirectly modulates immune activity and
probably disengages Listeria-induced suppression of these responses by inducing
a higher reserve of myeloid progenitors in the bone marrow, proliferation of
lymphocytes and increased INF-gamma levels.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16919825 [PubMed - indexed for MEDLINE]

23: Int Immunopharmacol. 2006 Sep;6(9):1394-403. Epub 2006 May 8.

Augmentation and proliferation of T lymphocytes and Th-1 cytokines by Withania
somnifera in stressed mice.

Khan B, Ahmad SF, Bani S, Kaul A, Suri KA, Satti NK, Athar M, Qazi GN.

Cell Biology Laboratory, Department of Pharmacology, Regional Research
Laboratory, Jammu Tawi 180001, India.

Stress has been associated with reports of both greater severity and
prolongation of diseases in patients with the infectious origin as well as other
immune-mediated diseases. Withania somnifera, an Indian medicinal plant used
widely in the treatment of many clinical conditions in India, was investigated
for its anti-stress properties using BALB/c mice subjected to chronic stress.
The study aimed to investigate chronic stress-induced alterations on Th1
lymphocyte subset distribution and corresponding cytokine secretion patterns.
Oral administration of chemically standardized and identified aqueous fraction
of W. somnifera root (WS) at the graded doses of 25, 50, 100 and 200 mg/kg p.o.
caused significant increase in the stress-induced depleted T-cell population and
increased the expression of Th1 cytokines in chronically stressed mice.

PMID: 16846833 [PubMed - indexed for MEDLINE]

24: Cancer Sci. 2006 Jul;97(7):658-64.

Chemotherapeutic efficacy of paclitaxel in combination with Withania somnifera
on benzo(a)pyrene-induced experimental lung cancer.

Senthilnathan P, Padmavathi R, Magesh V, Sakthisekaran D.

Department of Medical Biochemistry, ALM Postgraduate Institute of Basic Medical
Sciences, University of Madras, Taramani Campus, Chennai 600-113, India.

Lung cancer is one of the leading causes of cancer death in the world and is
notoriously difficult to treat effectively. In the present study, male Swiss
albino mice were divided into five groups of six animals each: group I animals
received corn oil orally and served as a control; group II cancer-induced
animals received benzo(a)pyrene (50 mg/kg bodyweight dissolved in corn oil,
orally) twice weekly for four successive weeks; group III cancer-bearing animals
(after 12 weeks of induction) were treated with paclitaxel (33 mg/kg bodyweight,
i.p.) once weekly for 4 weeks; group IV cancer-bearing animals were treated with
paclitaxel along with Withania somnifera (400 mg/kg bodyweight) orally once
weekly for 4 weeks; and group V animals constituted the drug control treated
with paclitaxel along with W. somnifera. The serum, lung and liver were
investigated biochemically for aryl hydrocarbon hydroxylase, gamma-glutamyl
transpeptidase, 5'-nucleotidase, lactate dehydrogenase and protein-bound
carbohydrate components (hexose, hexosamine and sialic acid). These enzyme
activities were increased significantly in cancer-bearing animals compared with
control animals. The elevation of these in cancer-bearing animals was indicative
of the persistent deteriorating effect of benzo(a)pyrene in cancer-bearing
animals. Our data suggest that paclitaxel, administered with W. somnifera, may
extend its chemotherapeutic effect through modulating protein-bound carbohydrate
levels and marker enzymes, as they are indicators of cancer. The combination of
paclitaxel with W. somnifera could effectively treat the benzo(a)pyrene-induced
lung cancer in mice by offering protection from reactive oxygen species damage
and also by suppressing cell proliferation.

PMID: 16827807 [PubMed - indexed for MEDLINE]

25: Mol Cancer Ther. 2006 Jun;5(6):1434-45.

Withanolides potentiate apoptosis, inhibit invasion, and abolish
osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB)
activation and NF-kappaB-regulated gene expression.

Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB.

Cytokine Research Laboratory, Department of Experimental Therapeutics, The
University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, TX 77030, USA.

The plant Withania somnifera Dunal (Ashwagandha), also known as Indian ginseng,
is widely used in the Ayurvedic system of medicine to treat tumors,
inflammation, arthritis, asthma, and hypertension. Chemical investigation of the
roots and leaves of this plant has yielded bioactive withanolides. Earlier
studies showed that withanolides inhibit cyclooxygenase enzymes, lipid
peroxidation, and proliferation of tumor cells. Because several genes that
regulate cellular proliferation, carcinogenesis, metastasis, and inflammation
are regulated by activation of nuclear factor-kappaB (NF-kappaB), we
hypothesized that the activity of withanolides is mediated through modulation of
NF-kappaB activation. For this report, we investigated the effect of the
withanolide on NF-kappaB and NF-kappaB-regulated gene expression activated by
various carcinogens. We found that withanolides suppressed NF-kappaB activation
induced by a variety of inflammatory and carcinogenic agents, including tumor
necrosis factor (TNF), interleukin-1beta, doxorubicin, and cigarette smoke
condensate. Suppression was not cell type specific, as both inducible and
constitutive NF-kappaB activation was blocked by withanolides. The suppression
occurred through the inhibition of inhibitory subunit of IkappaB alpha kinase
activation, IkappaB alpha phosphorylation, IkappaB alpha degradation, p65
phosphorylation, and subsequent p65 nuclear translocation. NF-kappaB-dependent
reporter gene expression activated by TNF, TNF receptor (TNFR) 1,
TNFR-associated death domain, TNFR-associated factor 2, and IkappaB alpha kinase
was also suppressed. Consequently, withanolide suppressed the expression of
TNF-induced NF-kappaB-regulated antiapoptotic (inhibitor of apoptosis protein 1,
Bfl-1/A1, and FADD-like interleukin-1beta-converting enzyme-inhibitory protein)
and metastatic (cyclooxygenase-2 and intercellular adhesion molecule-1) gene
products, enhanced the apoptosis induced by TNF and chemotherapeutic agents, and
suppressed cellular TNF-induced invasion and receptor activator of NF-kappaB
ligand-induced osteoclastogenesis. Overall, our results indicate that
withanolides inhibit activation of NF-kappaB and NF-kappaB-regulated gene
expression, which may explain the ability of withanolides to enhance apoptosis
and inhibit invasion and osteoclastogenesis.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16818501 [PubMed - indexed for MEDLINE]

26: Altern Med Rev. 2006 Jun;11(2):128-50.

Modulation of cytokine expression by traditional medicines: a review of herbal
immunomodulators.

Spelman K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M.

Clinical Division, Department of Herbal Medicine, Tai Sophia Institute, 7750
Montpelier Road, Laurel, MD 20723, USA. [email protected]

Modulation of cytokine secretion may offer novel approaches in the treatment of
a variety of diseases. One strategy in the modulation of cytokine expression may
be through the use of herbal medicines. A class of herbal medicines, known as
immunomodulators, alters the activity of immune function through the dynamic
regulation of informational molecules such as cytokines. This may offer an
explanation of the effects of herbs on the immune system and other tissues. For
this informal review, the authors surveyed the primary literature on medicinal
plants and their effects on cytokine expression, taking special care to analyze
research that utilized the multi-component extracts equivalent to or similar to
what are used in traditional medicine, clinical phytotherapy, or in the
marketplace. METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify
research on botanical medicines, in whole or standardized form, that act on
cytokine activity through different models, i.e., in vivo (human and animal), ex
vivo, or in vitro. RESULTS: Many medicinal plant extracts had effects on at
least one cytokine. The most frequently studied cytokines were IL-1, IL-6, TNF,
and IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus
comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea
purpurea, Grifola frondosa, Harpagophytum procumbens, Panax ginseng, Polygala
tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia,
Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple
cytokines. CONCLUSION: The in vitro and in vivo research demonstrates that the
reviewed botanical medicines modulate the secretion of multiple cytokines. The
reported therapeutic success of these plants by traditional cultures and modern
clinicians may be partially due to their effects on cytokines. Phytotherapy
offers a potential therapeutic modality for the treatment of many differing
conditions involving cytokines. Given the activity demonstrated by many of the
reviewed herbal medicines and the increasing awareness of the broad-spectrum
effects of cytokines on autoimmune conditions and chronic degenerative
processes, further study of phytotherapy for cytokine-related diseases and
syndromes is warranted.

Publication Types:
Review

PMID: 16813462 [PubMed - indexed for MEDLINE]

27: J Ethnopharmacol. 2006 Nov 3;108(1):152-4. Epub 2006 Apr 29.

An inventory of the ethnobotanicals used as anthelmintics in the southern Punjab
(Pakistan).

Jabbar A, Raza MA, Iqbal Z, Khan MN.

Ethnoveterinary Research and Development Centre, Department of Veterinary
Parasitology, University of Agriculture, Faisalabad-38040, Pakistan.
[email protected]

A survey was conducted in southern Punjab, Pakistan, in order to document
existing ethnobotanical knowledge by the herdsmen/key respondents about
anthelmintics in ruminants. A 3-satge process was used to document the plants
being used to treat and/or control helminthes. This paper describes 29 plants to
treat helminthosis in ruminants. The main plants used were Lamium amplexicaule
L., Mallotus philippinensis Muell., Withania somnifera (L.) Dunal., Azadirachta
indica A. Juss., and Citrullus colocynthis (L.) Schrad. A few of these plants
have been scientifically validated for their claim by herdsmen on modern lines
while majority of them still needs investigations. This documentation could
provide a foundation for the scientific study and verification of those plants
which merit such study.

PMID: 16730420 [PubMed - in process]

28: Vascul Pharmacol. 2006 Jun;44(6):406-10. Epub 2006 May 18.

Immunomodulatory role of Withania somnifera root powder on experimental induced
inflammation: An in vivo and in vitro study.

Rasool M, Varalakshmi P.

Department of Biosciences, Vellore Institute of Technology, Deemed University,
Vellore-632 014, India. [email protected]

The aqueous suspension of Withania somnifera root powder was investigated for
their in vivo and in vitro immunomodulatory properties. W. somnifera showed
potent inhibitory activity towards the complement system, mitogen induced
lymphocyte proliferation and delayed-type hypersensitivity reaction.
Administration of W. somnifera root powder did not have a significant effect on
humoral immune response in rats. Our results report immunosuppressive effect of
W. somnifera root powder, thus it could be a candidate for developing as an
immunosuppressive drug for the inflammatory diseases.

PMID: 16713367 [PubMed - indexed for MEDLINE]

29: Phytomedicine. 2007 Feb;14(2-3):136-42. Epub 2006 May 18.

Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in
hypercholesteremic rats.

Visavadiya NP, Narasimhacharya AV.

Department of Biosciences, Sardar Patel University, Vallabh Vidyanagar 388 120,
Gujarat, India.

Hypocholesteremic and antioxidant effects of Withania somnifera (WS) Dunal
(Solanaceae) were investigated in hypercholesteremic male albino rats. When the
root powder of WS was added to the diet at 0.75 and 1.5gm/rat/day,
hypercholesteremic animals registered significant decreases in total lipids
(-40.54%; -50.69%), cholesterol (-41.58%; -53.01%) and triglycerides (-31.25%; -
44.85%) in plasma. On the other hand, significant increases in plasma
HDL-cholesterol levels (+15.10%; +17.71%), HMG-CoA reductase activity (+19.51%;
+26.02%) and bile acid content (+24.64%; +30.52%) of liver were noted in these
animals. A similar trend was also noted in bile acid (+22.43%;+28.52%),
cholesterol (+14.21%; +17.68%) and neutral sterol (+12.40%; +18.85%) excretion
in the hypercholesteremic animals with WS administration. Further, a significant
decrease in lipid-peroxidation (-35.29%; -36.52%) occurred in WS administered
hypercholesteremic animals when compared to their normal counterparts. However,
it appeared that WS root powder is also effective in normal subjects for
decreasing lipid profiles.

PMID: 16713218 [PubMed - in process]

30: Phytother Res. 2006 Jul;20(7):614-7.

Hypolipidemic activity of aqueous extract of Withania coagulans Dunal in albino
rats.

Hemalatha S, Wahi AK, Singh PN, Chansouria JP.

Department of Pharmaceutics, Institute of Technology, Banaras Hindu University,
Varanasi 221005, India.

Administration of an aqueous extract of fruits of Withania coagulans (1 g/kg;
p.o.) to high fat diet induced hyperlipidemic rats for 7 weeks, significantly
reduced elevated serum cholesterol, triglycerides and lipoprotein levels. This
drug also showed hypolipidemic activity in triton induced hypercholesterolemia.
The histopathological examination of liver tissues of treated hyperlipidemic
rats showed comparatively lesser degenerative changes compared with
hyperlipidemic controls. The hypolipidemic effect of W. coagulans fruits was
found to be comparable to that of an Ayurvedic product containing Commiphora
mukkul.

PMID: 16691631 [PubMed - in process]

31: J Ethnopharmacol. 2006 Aug 11;107(1):107-15. Epub 2006 Apr 5.

Selective Th1 up-regulating activity of Withania somnifera aqueous extract in an
experimental system using flow cytometry.

Bani S, Gautam M, Sheikh FA, Khan B, Satti NK, Suri KA, Qazi GN, Patwardhan B.

Department of Pharmacology, Regional Research Laboratory, Jammu Tawi, India.
[email protected]

Withania somnifera (Ashwagandha) is reported to be immunoprotective and
immunoadjuvant. We studied its roots aqueous extract on T helper (Th) immunity
using flow cytometry. This extract was standardized with six withanolides as
marker compounds using HPLC. Once daily dose ranging from 25 to 400 mg/kg/p.o.
was used to study effect on Th1: IFN-gamma, IL-2 and Th2: IL-4 cytokine
modulation. We also studied effect on CD4 and CD8 in normal and immunesuppressed
mice. The results indicate that extract at 100 mg/kg resulted significant
selective up-regulation of Th1 response. Treatment with extract showed
significant increase in CD4 and CD8 counts as compared to control and
cyclopsorin A, with a faster recovery of CD4+ T cells in immunesuppressed
animals. Under immunesuppressed conditions, potentiation of cellular and humoral
immune responses of extract was comparable to levamisole. This study indicates
the selective Th1 up-regulating effect of extract and suggests its use for
selective Th1/Th2 modulation.

PMID: 16603328 [PubMed - indexed for MEDLINE]

32: J Pharm Pharmacol. 2006 Apr;58(4):513-9.

Withania somnifera improves bone calcification in calcium-deficient
ovariectomized rats.

Nagareddy PR, Lakshmana M.

Dept. of Pharmacology, Government College of Pharmacy, Bangalore, 560027, India.
[email protected]

Osteoporosis, characterized by reduction in bone density, is a significant
source of mortality among the elderly, particularly in oestrogen-deficient
women. We studied the effect of Withania somnifera (WS) root extract
(ethanolic), which contains oestrogen-like withanolides for anti-osteoporotic
activity. Female Sprague-Dawley rats were either sham operated (n = 12) or
ovariectomized (n = 12) and treated with WS/vehicle (65 mg kg(-1)), orally for
16 weeks (n = 12). All rats were allowed free access to a calcium-deficient diet
(0.04% Ca) and distilled water. At termination, urinary excretion of calcium
(Ca) and phosphorus (P) and serum levels of Ca, P and alkaline phosphatase (ALP)
were measured. Femur and tibia bones were processed for histological
(histology), morphological (scanning electron microscopy, SEM), biomechanical
strength (impact test) and mineral composition (ash) analysis. Ovariectomized
(OVX) rats showed a significant increase in serum ALP levels and urinary Ca and
P excretion. Histological findings revealed narrowed, and disappearance of,
trabeculae with widened medullary spaces in the OVX group. Ash analysis showed a
reduction in ash weight, percent ash, ash Ca, ash P and ash magnesium levels in
the OVX group. Further, SEM examination revealed metaphyseal bone loss in femurs
and impact test showed a reduction in biomechanical strength of tibias in OVX
rats. WS treatment markedly prevented the above changes in OVX rats and thus may
be a potential agent in the treatment of osteoporosis.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 16597369 [PubMed - indexed for MEDLINE]

33: Eur J Neurosci. 2006 Mar;23(6):1417-26.

Withanoside IV and its active metabolite, sominone, attenuate
Abeta(25-35)-induced neurodegeneration.

Kuboyama T, Tohda C, Komatsu K.

Division of Biofunctional Evaluation, Research Center for Ethnomedicine,
Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.

At the present, medication of dementia is limited to symptomatic treatments such
as the use of cholinesterase inhibitors. To cure dementia completely, that is
regaining neuronal function, reconstruction of neuronal networks is necessary.
Therefore, we have been exploring antidementia drugs based on reconstructing
neuronal networks in the damaged brain and found that withanoside IV (a
constituent of Ashwagandha; the root of Withania somnifera) induced neurite
outgrowth in cultured rat cortical neurons. Oral administration of withanoside
IV (10 micromol/kg/day) significantly improved memory deficits in
Abeta(25-35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons,
dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified
as the main metabolite after oral administration of withanoside IV. Sominone (1
microM) induced axonal and dendritic regeneration and synaptic reconstruction
significantly in cultured rat cortical neurons damaged by 10 microM
Abeta(25-35). These data suggest that orally administrated withanoside IV may
ameliorate neuronal dysfunction in Alzheimer's disease and that the active
principle after metabolism is sominone.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16553605 [PubMed - indexed for MEDLINE]

34: J Ethnopharmacol. 2006 Jul 19;106(3):403-7. Epub 2006 Mar 13.

Anti-plasmodial activity and toxicity of extracts of plants used in traditional
malaria therapy in Meru and Kilifi Districts of Kenya.

Kirira PG, Rukunga GM, Wanyonyi AW, Muregi FM, Gathirwa JW, Muthaura CN, Omar
SA, Tolo F, Mungai GM, Ndiege IO.

Department of Chemistry, School of Pure & Applied Sciences, Kenyatta University,
P.O. Box 43844, Nairobi 00100 GPO, Kenya.

The methanol and aqueous extracts of 10 plant species (Acacia nilotica,
Azadirachta indica, Carissa edulis, Fagaropsis angolensis, Harrissonia
abyssinica, Myrica salicifolia, Neoboutonia macrocalyx, Strychnos heningsii,
Withania somnifera and Zanthoxylum usambarensis) used to treat malaria in Meru
and Kilifi Districts, Kenya, were tested for brine shrimp lethality and in vitro
anti-plasmodial activity against chloroquine-sensitive and chloroquine-resistant
strains of Plasmodium falciparum (NF54 and ENT30). Of the plants tested, 40% of
the methanol extracts were toxic to the brine shrimp (LD(50)<100micro/ml), while
50% showed in vitro anti-plasmodial activity (IC(50)<100microg/ml). The methanol
extract of the stem bark of N. macrocalyx had the highest toxicity to brine
shrimp nauplii (LD(50) 21.04+/-1.8microg/ml). Methanol extracts of the rest of
the plants exhibited mild or no brine shrimp toxicity (LD(50)>50microg/ml). The
aqueous extracts of N. macrocalyx had mild brine shrimp toxicity (LD(50)
41.69+/-0.9microg/ml), while the rest were lower (LD(50)>100microg/ml). The
methanol extracts of F. angolensis and Zanthoxylum usambarense had IC(50) values
<6microg/ml while the aqueous ones had values between 6 and 15microg/ml, against
both chloroquine-sensitive and resistant P. falciparum strains. The results
support the use of traditional herbs for anti-malarial therapy and demonstrate
their potential as sources of drugs.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16530996 [PubMed - indexed for MEDLINE]

35: Comp Biochem Physiol C Toxicol Pharmacol. 2006 Jun;143(2):158-61. Epub 2006
Mar 2.

A glycoprotein from a folk medicinal plant, Withania somnifera, inhibits
hyaluronidase activity of snake venoms.

Machiah DK, Girish KS, Gowda TV.

Department of Pathology, Emory School of Medicine, Atlanta, Georgia, USA.

Venom hyaluronidases help in rapid spreading of the toxins by destroying the
integrity of the extra-cellular matrix of the tissues in the victims. A
hyaluronidase inhibitor (WSG) is purified from a folk medicinal plant, Withania
somnifera. The glycoprotein inhibited the hyaluronidase activity of cobra (Naja
naja) and viper (Daboia russelii) venoms, which was demonstrated by zymogram
assay and staining of the skin tissues for differential activity. WSG completely
inhibited the activity of the enzyme at a concentration of 1:1 w/w of venom to
WSG. Thus we are able to demonstrate that the glycoprotein inhibits
hyaluronidase activity of the venoms. External application of the plant extract
as an antidote in rural parts of India to snakebite victims appears to have a
scientific basis.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 16513428 [PubMed - in process]

36: Biochimie. 2006 Jun;88(6):701-10. Epub 2006 Jan 26.

Purification of a post-synaptic neurotoxic phospholipase A2 from Naja naja venom
and its inhibition by a glycoprotein from Withania somnifera.

Machiah DK, Gowda TV.

Department of Infectious Disease, Emory University, Atlanta 30030 Georgia, USA.

A post-synaptic neurotoxic phospholipase A(2) (PLA(2)) has been purified from
Indian cobra Naja naja venom. It was associated with a peptide in the venom. The
association was disrupted using 8 M urea. It is denoted to be a basic protein by
its behavior on both ion exchange chromatography and electrophoresis. It is
toxic to mice, LD(50) 1.9 mg/kg body weight (ip). It is proved to be
post-synaptic PLA(2) by chymographic experiment using frog nerve-muscle
preparation. A glycoprotein, (WSG) was isolated from a folk medicinal plant
Withania somnifera. The WSG inhibited the phospholipase A(2) activity of
NN-XIa-PLA(2,) isolated from the cobra venom, completely at a mole-to-mole ratio
of 1:2 (NN-XIa-PLA(2): WSG) but failed to neutralize the toxicity of the
molecule. However, it reduced the toxicity as well as prolonged the death time
of the experimental mice approximately 10 times when compared to venom alone.
The WSG also inhibited several other PLA(2) isoforms from the venom to varying
extent. The interaction of the WSG with the PLA(2) is confirmed by fluorescence
quenching and gel-permeation chromatography. Chemical modification of the active
histidine residue of PLA(2) using p-brophenacyl bromide resulted in the loss of
both catalytic activity as well as neurotoxicity of the molecule. These findings
suggest that the venom PLA(2) has multiple sites on it; perhaps some of them are
overlapping. Application of the plant extract on snakebite wound confirms the
medicinal value associated with the plant.

Publication Types:
In Vitro
Research Support, Non-U.S. Gov't

PMID: 16494989 [PubMed - indexed for MEDLINE]

37: Phytomedicine. 2006 Mar;13(4):222-9. Epub 2005 Sep 27.

Protective effect of CardiPro against doxorubicin-induced cardiotoxicity in
mice.

Mohan IK, Kumar KV, Naidu MU, Khan M, Sundaram C.

Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical
Sciences, Punjagutta, Hyderabad, 500082, India.

The effect of CardiPro, a polyherbal formulation, with an antioxidant property,
has been studied on doxorubicin (DXR)-induced cardiotoxicity in mice. CardiPro
(150 mg/kg b.w., twice daily was administered orally for 7 weeks along with four
equal injections (each containing 4.0 mg/kg b.w., DXR) intraperitoneally, once
weekly (cumulative dose 16 mg/kg). After a 3-week post DXR treatment period,
cardiotoxicity was assessed by noting mortality, volume of ascites, liver
congestion, changes in heart weight, myocardial lipid peroxidation, antioxidant
enzymes and histology of heart. DXR-treated animals showed higher mortality
(50%) and more ascites. Myocardial SOD and glutathione peroxidase activity were
decreased and lipid peroxidation was increased. Histology of heart of
DXR-treated animals showed loss of myofibrils and focal cytoplasmic
vacuolization. CardiPro significantly protected the mice from DXR-induced
cardiotoxic effects as evidenced by lower mortality (25%), less ascites,
myocardial lipid peroxidation, normalization of antioxidant enzymes and minimal
damage to the heart histologically. Our data confirm the earlier reports that
DXR cardiotoxicity is associated with the free radical-induced tissue damage.
Administration of CardiPro, with an antioxidant property, protected the
DXR-induced cardiotoxicity in mice.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 16492523 [PubMed - indexed for MEDLINE]

38: Phytother Res. 2006 Feb;20(2):140-6.

Effect of Withania somnifera root extract on reserpine-induced orofacial
dyskinesia and cognitive dysfunction.

Naidu PS, Singh A, Kulkarni SK.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab
University, Chandigarh 160014, India.

Tardive dyskinesia is one of the major side effects of long-term neuroleptic
treatment. The pathophysiology of this disabling and commonly irreversible
movement disorder is still obscure. Vacuous chewing movements in rats are widely
accepted as an animal model of tardive dyskinesia. Oxidative stress and products
of lipid peroxidation are implicated in the pathophysiology of tardive
dyskinesia. Repeated treatment with reserpine (1.0 mg/kg) on alternate days for
a period of 5 days (days 1, 3 and 5) significantly induced vacuous chewing
movements and tongue protrusions in rats. Chronic treatment with Withania
somnifera root extract (Ws) for a period of 4 weeks to reserpine treated animals
significantly and dose dependently (50 and 100 mg/kg) reduced the
reserpine-induced vacuous chewing movements and tongue protrusions. Reserpine
treated animals also showed poor retention of memory in the elevated plus maze
task paradigm. Chronic Ws administration significantly reversed
reserpine-induced retention deficits. Biochemical analysis revealed that chronic
reserpine treatment significantly induced lipid peroxidation and decreased the
glutathione (GSH) levels in the brains of rats. Chronic reserpine treated rats
showed decreased levels of antioxidant defense enzymes, superoxide dismutase
(SOD) and catalase. Chronic administration of Ws root extract dose dependently
(50 and 100 mg/kg) and significantly reduced the lipid peroxidation and restored
the decreased glutathione levels by chronic reserpine treatment. It also
significantly reversed the reserpine-induced decrease in brain SOD and catalase
levels in rats. The major findings of the present study indicate that oxidative
stress might play an important role in the pathophysiology of reserpine-induced
abnormal oral movements. In conclusion, Withania somnifera root extract could be
a useful drug for the treatment of drug-induced dyskinesia. Copyright 2006 John
Wiley & Sons, Ltd.

PMID: 16444668 [PubMed - indexed for MEDLINE]

39: Indian J Exp Biol. 2006 Jan;44(1):45-8.

Effect of BR-16A (Mentat), a polyherbal formulation on drug-induced catalepsy in
mice.

Kumar A, Kulkarni SK.

University Institute of Pharmaceutical Science, Panjab University, Chandigarh
160 014, India.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the
selective loss of dopamine (DA) neurons of the substantia nigra pars compacta
(SNc). The events, which trigger and/or mediate the loss of nigral DA neurons,
however, remain unclear. Neuroleptic-induced catalepsy has long been used as an
animal model for screening drugs for Parkinsonism. Administration of haloperidol
(1 mg/kg, ip) or reserpine (2 mg/kg, ip) significantly induced catalepsy in
mice. BR-16A (50 and 100 mg/kg, po), a polyherbal formulation or ashwagandha (50
and 100 mg/kg, po), significantly reversed the haloperidol or reserpine-induced
catalepsy. The results indicate that BR-16A or ashwagandha has protective effect
against haloperidol or reserpine-induced catalepsy and provide hope that BR-16A
could be used in preventing the drug-induced extrapyramidal side effects and may
offer a new therapeutic approach to the treatment of Parkinson's disease.

PMID: 16430090 [PubMed - indexed for MEDLINE]

40: J Ethnopharmacol. 2006 May 24;105(3):336-41. Epub 2006 Jan 10.

Evaluation of the effect of Withania somnifera root extracts on cell cycle and
angiogenesis.

Mathur R, Gupta SK, Singh N, Mathur S, Kochupillai V, Velpandian T.

Department of Pharmacology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi 110029, India.

In the Indian System of Medicine, the medicinal plant, Withania somnifera Dunal
(Solanaceae) finds application for numerous ailments including cancer. This
study explores the mechanism(s) underlying this property. The hydroalcoholic
extract of the roots (WS) was partitioned between chloroform (WS-chloroform) and
water (WS-water). Further, WS-chloroform was fractionated (A1-A12) by
reverse-phase column chromatography and their withanolide content was quantified
by high-performance liquid chromatography (HPLC). Preliminarily, the
anti-proliferative activity of all the extracts and fractions was screened
against human laryngeal carcinoma (Hep2) cells by microculture tetrazolium assay
(MTT). Two extracts (WS and WS-chloroform) and three fractions (A4, A5 and A6)
negatively affected Hep2 viability at the concentration of 25 microg/ml and
these were further investigated pharmacologically. Flow cytometry revealed cell
cycle block and accumulation of hypoploid (sub G1) cells as the mode of
anti-proliferative activity of all but A4. Their anti-angiogenic potential was
investigated by a chickchorio-allantoic membrane (CAM) wherein a significant
inhibition (p<0.0001) of vascular endothelium growth factor (VEGF), induced
neovascularization was recorded. The effect was confirmed in vivo by mouse
sponge implantation method. These findings suggest that the roots of Withania
somnifera possess cell cycle disruption and anti-angiogenic activity, which may
be a critical mediator for its anti-cancer action.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16412596 [PubMed - indexed for MEDLINE]

41: J Plant Physiol. 2006 Feb;163(2):220-3. Epub 2005 Sep 2.

Regeneration of plants from alginate-encapsulated shoot tips of Withania
somnifera (L.) Dunal, a medicinally important plant species.

Singh AK, Varshney R, Sharma M, Agarwal SS, Bansal KC.

National Research Centre on Plant Biotechnology, Indian Agricultural Research
Institute, New Delhi-110 012, India.

A protocol was developed for plant regeneration from encapsulated shoot tips
collected from in vitro proliferated shoots of Withania somnifera. The best gel
composition was achieved using 3% sodium alginate and 75 mM CaCl2.2H2O. The
maximum percentage response (87%) for conversion of encapsulated shoot tips into
plantlets was achieved on MS medium supplemented with 0.5 mg/l IBA after 5 weeks
of culture. The conversion of encapsulated shoot tips into plantlets also
occurred when calcium alginate beads having entrapped propagules were directly
sown in autoclaved soilrite moistened with 14-MS salts.

PMID: 16399013 [PubMed - indexed for MEDLINE]

42: Ann N Y Acad Sci. 2005 Nov;1056:261-78.

Antiulcer and Antioxidant Activity of Asparagus racemosus WILLD and Withania
somnifera DUNAL in Rats.

Bhatnagar M, Sisodia SS, Bhatnagar R.

Department of Zoology, University College of Science, Mohan Lal Sukhadia
University, Udaipur-313001, India. [email protected]

Comparative study of the antiulcer and antisecretory activity of Asparagus
racemosus Willd (Shatawari) and Withania somnifera Dunal (Ashwagandha) root
extract with a standard drug, ranitidine, in various models of gastric ulcer in
rats is presented. Ulcer was induced by the indomethacin (NSAID) and swim
(restraint) stress treatment. Results demonstrated that A. racemosus as well as
W. somnifera methanolic extract (100 mg/kg BW/day p.o.) given orally for 15 days
significantly reduced the ulcer index, volume of gastric secretion, free
acidity, and total acidity. A significant increase in the total carbohydrate and
total carbohydrate/protein ratio was also observed. Study also indicated an
increase in antioxidant defense, that is, enzymes superoxide dismutase,
catalase, and ascorbic acid, increased significantly, whereas a significant
decrease in lipid peroxidation was observed. A. racemosus was more effective in
reducing gastric ulcer in indomethacin-treated gastric ulcerative rats, whereas
W. somnifera was effective in stress-induced gastric ulcer. Results obtained for
both herbal drugs were comparable to those of the standard drug ranitidine.

PMID: 16387694 [PubMed - in process]

43: Chem Biol Interact. 2006 Feb 25;159(3):180-5. Epub 2005 Dec 22.

Enhancement of antitumor effect of paclitaxel in combination with
immunomodulatory Withania somnifera on benzo(a)pyrene induced experimental lung
cancer.

Senthilnathan P, Padmavathi R, Banu SM, Sakthisekaran D.

Department of Medical Biochemistry, Dr. ALM Postgraduate Institute of Basic
Medical Sciences, University of Madras, Taramani, Chennai 600113, India.
[email protected]

The current experimental work deals with the immunomodulatory studies on the
extract of Withania somnifera (L.) Dunal root powder against benzo(a)pyrene
induced lung cancer in male Swiss albino mice. In our previous study, we
reported the antioxidant and anticarcinogenic effect of W. somnifera (L.) Dunal
along with paclitaxel. Immune dysfunction has been found to be associated with
cancer and chemotherapy. Benzo(a)pyrene induced cancer animals were treated with
400mg/kg bodyweight of W. somnifera (L.) Dunal extract for 30 days significantly
alters the levels of immunocompetent cells, immune complexes and
immunoglobulins. Based on the data, the carcinogen as well as the paclitaxel
affects the immune system, the toxic side effects on the immune system is more
reversible and more controllable by W. somnifera (L.) Dunal. These results
concluded the immunomodulatory activity of W. somnifera (L.) Dunal extract,
which is a known immunomodulator in indigenous medicine.

PMID: 16375880 [PubMed - indexed for MEDLINE]

44: Ned Tijdschr Geneeskd. 2005 Nov 19;149(47):2637-8.

[Thyrotoxicosis following the use of ashwagandha]

[Article in Dutch]

van der Hooft CS, Hoekstra A, Winter A, de Smet PA, Stricker BH.

Inspectie voor de Gezondheidszorg, sectie Geneesmiddelenbewaking, Postbus
16.119, 2500 BC Den Haag.

A 32-year-old healthy woman developed thyrotoxicosis while taking capsules that
contained ashwagandha herbal extract for symptoms of chronic fatigue. She was
not taking any other remedies or medications. During the first few weeks, she
took the capsules only occasionally without any symptoms, but after increasing
the dose, she experienced clinical symptoms indicative of thyrotoxicosis. This
was confirmed by laboratory assessment. The symptoms resolved spontaneously
after discontinuation of the ashwagandha capsules and laboratory values
normalised. To our knowledge, this relationship has not been reported previously
in humans. Data from animal studies, however, have suggested that ashwagandha
can increase serum concentrations of thyroid hormones. This case study suggests
that thyrotoxicosis is a potentially serious side effect of ashwagandha.

Publication Types:
Case Reports
English Abstract

PMID: 16355578 [PubMed - indexed for MEDLINE]

45: Phytochemistry. 2005 Dec;66(23):2702-7. Epub 2005 Nov 15.

Unusually sulfated and oxygenated steroids from Withania somnifera.

Misra L, Lal P, Sangwan RS, Sangwan NS, Uniyal GC, Tuli R.

Central Institute of Medicinal and Aromatic Plants, P.O.-CIMAP, Lucknow, UP 226
015, India. [email protected]

Four (1, 8-10) and six known (2-7) withanolides were isolated from the leaves of
Withania somnifera. Among the new compounds, 10 possessed the rare 3-O-sulfate
group with the saturation in A ring and 9 contained unusual 1,4-dien-3-one
group. Compound 8 did not have usual 2,3 unsaturation in A ring while 1 had the
rare C-16 double bond. The structures of all the compounds were elucidated by
spectroscopic methods and chemical transformation.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16293277 [PubMed - indexed for MEDLINE]

46: Life Sci. 2006 Jan 25;78(9):1010-4. Epub 2005 Sep 6.

Modulation of TCA cycle enzymes and electron transport chain systems in
experimental lung cancer.

Senthilnathan P, Padmavathi R, Magesh V, Sakthisekaran D.

Department of Medical Biochemistry, Dr. ALM Postgraduate Institute of Basic
Medical Sciences, University of Madras, Taramani, Chennai 600 113, India.
[email protected]

The modulatory effect of Withania somnifera along with paclitaxel on
tricarboxylic acid (TCA) cycle key enzymes and electron transport chain
complexes were investigated against lung cancer induced by benzo(a)pyrene in
Swiss albino mice. Decreased activities of TCA cycle key enzymes such as
isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate
dehydrogenase (MDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) in lung
cancer bearing animals were observed. Upon W. somnifera along with paclitaxel
administration the above biochemical changes were inclined towards normal
control animal values. Activities of mitochondrial enzymes and electron
transport complexes were analyzed in the experimental groups to determine the
efficiency of energy production. This study further confirms the
chemotherapeutic effect of W. somnifera along with paclitaxel which is found to
be more effective in the treatment of lung cancer. Thus these results are
consistent with our hypothesis that the combination chemotherapy of W. somnifera
along with paclitaxel as a promising chemotherapeutic agent.

PMID: 16143346 [PubMed - indexed for MEDLINE]

47: Biochem Biophys Res Commun. 2005 Aug 19;334(1):276-87.

Withanolides, a new class of natural cholinesterase inhibitors with calcium
antagonistic properties.

Choudhary MI, Nawaz SA, ul-Haq Z, Lodhi MA, Ghayur MN, Jalil S, Riaz N, Yousuf
S, Malik A, Gilani AH, ur-Rahman A.

Dr. Panjwani Center for Molecular Medicine and Drug Research, International
Center for Chemical Sciences, University of Karachi, Karachi-75270, Pakistan.
[email protected]

The withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania
somnifera, respectively, inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and
butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent
fashion with IC50 values ranging between 20.5 and 49,2 microm and 29.0 and 85.2
microm for AChE and BChE, respectively. Lineweaver-Burk as well as Dixon plots
and their secondary replots indicated that compounds 1, 3, and 5 are the linear
mixed-type inhibitors of AChE, while 2 and 4 are non-competitive inhibitors of
AChE with K(i) values ranging between 20.0 and 45.0 microm. All compounds were
found to be non-competitive inhibitors of BChE with K(i) values ranging between
27.7 and 90.6 microm. Molecular docking study revealed that all the ligands are
completely buried inside the aromatic gorge of AChE, while compounds 1, 3, and 5
extend up to the catalytic triad. A comparison of the docking results showed
that all ligands generally adopt the same binding mode and lie parallel to the
surface of the gorge. The superposition of the docked structures demonstrated
that the non-flexible skeleton of the ligands always penetrates the aromatic
gorge through the six-membered ring A, allowing their simultaneous interaction
with more than one subsite of the active center. The affinity of ligands with
AChE was found to be the cumulative effects of number of hydrophobic contacts
and hydrogen bonding. Furthermore, all compounds also displayed dose-dependent
(0.005-1.0 mg/mL) spasmolytic and Ca2+ antagonistic potentials in isolated
rabbit jejunum preparations, compound 4 being the most active with an ED50 value
of 0.09 +/- 0.001 mg/mL and 0.22 +/- 0.01 microg/mL on spontaneous and K+
-induced contractions, respectively. The cholinesterase inhibitory potential
along with calcium antagonistic ability and safe profile in human neutrophil
viability assay could make compounds 1-5 possible drug candidates for further
study to treat Alzheimer's disease and associated problems.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16108094 [PubMed - indexed for MEDLINE]

48: Phytother Res. 2005 May;19(5):409-15.

Effect of Dianex, a herbal formulation on experimentally induced diabetes
mellitus.

Mutalik S, Chetana M, Sulochana B, Devi PU, Udupa N.

College of Pharmaceutical Sciences, Manipal, Karnataka, India.

Dianex, a polyherbal formulation consisting of the aqueous extracts of Gymnema
sylvestre, Eugenia jambolana, Momordica charantia Azadirachta indica, Cassia
auriculata, Aegle marmelose, Withania somnifera and Curcuma longa was screened
for hypoglycemic activity in normal and streptozotocin induced diabetic mice.
Dianex was administered in different doses of 100-500 mg/kg/day orally in acute
(6 h) and long-term (6 weeks) studies. Blood glucose levels were checked 2-6 h
after treatment in acute studies and every 2 weeks in long-term studies. Body
weight was recorded on the first and final day of the treatment in the long-term
studies with diabetic mice. After 6 weeks, high-density lipoprotein,
triglycerides, total cholesterol, alanine transaminase (ALT), aspertate
transaminase (AST), urea and creatinine were estimated in serum of the diabetic
mice. Glycogen and total protein levels were estimated in the liver. Also, the
liver and pancreas was subjected to histological examination. Oral glucose
tolerance and in vitro free radical scavenging activity was also studied.Dianex
produced significant (p<0.05) hypoglycemic activity at 250-500 mg/kg doses in
both normal and diabetic mice in acute and long-term studies. The body weight of
diabetic mice significantly (p<0.05) increased with all tested doses of Dianex.
The elevated triglycerides, cholesterol, ALT, AST, urea and creatinine levels in
diabetic mice were significantly (p<0.05) reduced at the doses of 250 and 500
mg/kg. The liver glycogen and protein levels were both significantly (p<0.05)
increased in diabetic mice at 250 and 500 mg/kg doses. Dianex increased the
glucose tolerance significantly (p<0.05) in both normal and diabetic mice at all
the doses tested. Histopathological examination showed that the formulation
decreased streptozotocin induced injury to the tissues at all the doses tested.
It produced significant (p<0.05) free radical scavenging activity against ABTS+,
DPPH and hydroxyl free radicals at the concentrations ranging between 10-1000
microg/ml.Thus, in the present study, Dianex produced significant hypoglycemic
activity in both normal and diabetic animals. It also reversed other diabetic
complications in diabetic mice at 250 and 500 mg/kg doses. In our earlier study,
Dianex was well tolerated in laboratory animals at higher doses (upto 10 g/kg in
mice, acute toxicity; up to 2.5 g/kg in rats, subacute toxicity studies for 30
days) without exhibiting any toxic manifestation. Hence, Dianex may be useful in
the treatment of diabetes mellitus. Copyright (c) 2005 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 16106394 [PubMed - indexed for MEDLINE]

49: Am J Clin Pathol. 2005 Aug;124(2):229-36.

Effect of Brazilian, Indian, Siberian, Asian, and North American ginseng on
serum digoxin measurement by immunoassays and binding of digoxin-like
immunoreactive components of ginseng with Fab fragment of antidigoxin antibody
(Digibind).

Dasgupta A, Reyes MA.

Department of Pathology and Laboratory Medicine, University of Texas-Houston
Medical School, 77030, USA.

We compared Brazilian, Indian, Siberian, Asian, and North American ginseng for
potential interference with 3 digoxin immunoassays: fluorescence polarization
(FPIA), microparticle enzyme (MEIA), and Tina-quant (Roche Diagnostics,
Indianapolis, IN). We supplemented aliquots of a drug-free serum pool with
ginseng extracts representing expected in vivo concentrations and overdose. We
observed apparent digoxin-like immunoreactivity with FPIA, modest
immunoreactivity with MEIA, and no apparent digoxin immunoreactivity with the
Tina-quant with all ginsengs except Brazilian, which showed no immunoreactivity
with any assay. When aliquots of serum pools prepared from patients receiving
digoxin were supplemented with ginsengs, we observed falsely elevated digoxin
values with FPIA, falsely lower digoxin values (negative interference) with
MEIA, and no interference with the Tina-quant. Digoxin-like immunoreactive
components of various ginsengs have moderate protein binding; monitoring free
digoxin concentrations does not eliminate such interference. We also observed
that Digibind (Burroughs Wellcome, Research Triangle Park, NC) can bind free
digoxin-like immunoreactive components of ginsengs; such effects can be
monitored by measuring apparent free digoxin concentrations. Indian, Asian, and
North American ginsengs interfere with serum digoxin measurement by FPIA and
MEIA; the Tina-quant is free of such interference. Digibind can bind free
digoxin-like immunoreactive components of ginseng.

Publication Types:
Comparative Study

PMID: 16040294 [PubMed - indexed for MEDLINE]

50: Nat Prod Res. 2005 Sep;19(6):567-71.

In vitro enzyme inhibition activities of crude ethanolic extracts derived from
medicinal plants of Pakistan.

Khattak S, Saeed-Ur-Rehman, Shah HU, Khan T, Ahmad M.

Department of Chemistry, University of Peshawar, Peshawar - 25120, Pakistan.
[email protected]

Twenty two crude ethanolic extracts from 14 indigenous medicinal plants were
subjected to enzyme inhibition screening against acetylcholinesterase (AChE),
butyrylcholinesterase (BChE) and lipoxygenase enzymes (LO). Three extracts
showed activity against AChE, nine extracts were found to be active against BChE
and four extracts inhibited the enzyme LO. The most significant inhibition
activities (> or =50%) were found in extracts derived from Aloe vera (leaves),
Alpinia galanga (rhizome), Curcuma longa (rhizome), Cymbopogon citratus
(leaves), Ocimum americanum (leaves), Ocimum americanum (stem) and Withania
somnifera (roots).

Publication Types:
In Vitro

PMID: 16010821 [PubMed - indexed for MEDLINE]

51: Phytomedicine. 2005 Jun;12(6-7):468-81.

Adaptogenic activity of glyco-peptido-lipid fraction from the alcoholic extract
of Trichopus zeylanicus Gaerten (part II).

Singh B, Chandan BK, Sharma N, Singh S, Khajuria A, Gupta DK.

Department of Pharmacology, Regional Research Laboratory, Canal Road,
Jammu--Tawi, India. [email protected]

Anti-stress activity was carried out on glyco-peptido-lipid (AF) fraction from
the alcoholic extract of Trichopus zeylanicus Gaerten and demonstrated against a
battery of tests in rats and mice. AF exhibited significant anti-stress activity
in dose-related manners in all the parameters studied against different models
used to induce non-specific stress viz physical and chemically. The major
parameters studied were immobilization induced gastric ulceration,
adjuvant-induced trauma (Stress); humoral antibody synthesis in normal and
immuno-suppressed mice and delayed type of hypersensitivity (DTH) reaction,
chemically stress-induced alteration in hepatic function and anti-oxidant
activity. The extract of Withania somnifera root (a commercial preparation
available locally, Dabur India ltd.) was used to compare the results. In the
safety evaluation study the maximum tolerance dose (MTD) and oral LD50 were
found to be more than 3000 mg/kg, with no signs of abnormalities or any
mortality observed for 15 days period under observation after single dose of
drug administration. Feeding behaviour and fecal output were normal.

PMID: 16008124 [PubMed - indexed for MEDLINE]

52: Indian J Med Res. 2005 May;121(5):683-90.

Influence of Yoga and Ayurveda on self-rated sleep in a geriatric population.

Manjunath NK, Telles S.

Swami Vivekananda Yoga Research Foundation, Bangalore, India.

BACKGROUND AND OBJECTIVE: Sleep in older persons is characterized by decreased
ability to stay asleep, resulting in fragmented sleep and reduced daytime
alertness. Pharmacological treatment of insomnia in older persons is associated
with hazardous side effects. Hence, the present study was designed to compare
the effects of Yoga and Ayurveda on the self rated sleep in a geriatric
population. METHODS: Of the 120 residents from a home for the aged, 69 were
stratified based on age (five year intervals) and randomly allocated to three
groups i.e., Yoga (physical postures, relaxation techniques, voluntarily
regulated breathing and lectures on yoga philosophy), Ayurveda (a herbal
preparation), and Wait-list control (no intervention). The groups were evaluated
for self-assessment of sleep over a one week period at baseline, and after three
and six months of the respective interventions. RESULTS: The Yoga group showed a
significant decrease in the time taken to fall asleep (approximate group average
decrease: 10 min, P<0.05), an increase in the total number of hours slept
(approximate group average increase: 60 min, P< 0.05) and in the feeling of
being rested in the morning based on a rating scale (P<0.05) after six months.
The other groups showed no significant change. INTERPRETATION AND CONCLUSION:
Yoga practice improved different aspects of sleep in a geriatric population.

Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 15937373 [PubMed - indexed for MEDLINE]

53: Hum Exp Toxicol. 2005 Mar;24(3):137-47.

Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced
Parkinsonism in rats.

Ahmad M, Saleem S, Ahmad AS, Ansari MA, Yousuf S, Hoda MN, Islam F.

Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology,
Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.

6-Hydroxydopamine (6-OHDA) is one of the most widely used rat models for
Parkinson's disease. There is ample evidence in the literature that 6-OHDA
elicits its toxic manifestations through oxidant stress. In the present study,
we evaluated the anti-parkinsonian effects of Withania somnifera extract, which
has been reported to have potent anti-oxidant, anti-peroxidative and free
radical quenching properties in various diseased conditions. Rats were
pretreated with 100, 200 and 300 mg/kg b.w. of the W. somnifera extract orally
for 3 weeks. On day 21, 2 microL of 6-OHDA (10 microg in 0.1% in ascorbic
acid-saline) was infused into the right striatum while sham operated group
received 2 microL of the vehicle. Three weeks after 6-OHDA injections, rats were
tested for neurobehavioral activity and were killed 5 weeks after lesioning for
the estimation of lipidperoxidation, reduced glutathione content, activities of
glutathione-S-transferase, glutathione reductase, glutathione peroxidase,
superoxide dismutase and catalase, catecholamine content, dopaminergic D2
receptor binding and tyrosine hydroxylase expression. W. somnifera extract was
found to reverse all the parameters significantly in a dose-dependent manner.
Thus, the study demonstrates that the extract of W. somnifera may be helpful in
protecting the neuronal injury in Parkinson's disease.

PMID: 15901053 [PubMed - indexed for MEDLINE]

54: Fitoterapia. 2005 Jun;76(3-4):355-8.

Cytotoxicity of plants used in traditional medicine in Yemen.

Al-Fatimi M, Friedrich U, Jenett-Siems K.

Department of Pharmacognosy, Faculty of Medicine and Health Sciences, Aden
University, P.O. Box 5411-Maalla, Aden, Yemen.

Twenty-five extracts obtained from 14 plant species used in the traditional
medicine in Yemen have been screened for cytotoxic activity against human
ECV-304 cells. Extracts of Dracaena cinnabari, Eucalyptus camaldulensis, Euclea
divinorum, Euphorbia cactus, Pulicaria crispa, and Withania somnifera displayed
a remarkable activity.

PMID: 15890471 [PubMed - indexed for MEDLINE]

55: Evid Based Complement Alternat Med. 2005 Mar;2(1):99-105. Epub 2005 Feb 9.

Roots of Withania somnifera Inhibit Forestomach and Skin Carcinogenesis in Mice.

Padmavathi B, Rath PC, Rao AR, Singh RP.

We evaluated the cancer chemopreventive efficacy of the Withania somnifera root,
which has been used in the Indian traditional medicine system for many centuries
for the treatment of various ailments. Since, studies showing its
mechanism-based cancer chemopreventive efficacy are limited, this was
investigated in the present study. We studied the effect of dietary
administration of Withania root on hepatic phase I, phase II and antioxidant
enzymes by estimation of its level/activity, as well as in attenuating
carcinogen-induced forestomach and skin tumorigenesis in the Swiss albino mouse
model. Our findings showed that roots of W.somnifera inhibit phase I, and
activates phase II and antioxidant enzymes in the liver. Further, in a long-term
tumorigenesis study, Withania inhibited benzo(a)pyrene-induced forestomach
papillomagenesis, showing up to 60 and 92% inhibition in tumor incidence and
multiplicity, respectively. Similarly, Withania inhibited
7,12-dimethylbenzanthracene-induced skin papillomagenesis, showing up to 45 and
71% inhibition in tumor incidence and multiplicity. In both studies, Withania
showed no apparent toxic effects in mice as monitored by the body weight gain
profile. Together, these findings suggest that W.somnifera root has
chemopreventive efficacy against forestomach and skin carcinogenesis and
warrants the identification and isolation of active compounds responsible for
its anticancer effects, which may provide the lead for the development of
antitumor agents.

PMID: 15841284 [PubMed - as supplied by publisher]

56: Phytomedicine. 2005 Mar;12(3):229-35.

Antibacterial efficacy of Withania somnifera (ashwagandha) an indigenous
medicinal plant against experimental murine salmonellosis.

Owais M, Sharad KS, Shehbaz A, Saleemuddin M.

Aligarh Muslim University, Aligarh, India. [email protected]

In the present study, we evaluated the antibacterial activity of ashwagandha
[Withania somnifera L. Dunal (Solanaceae; root and leaves)], an Indian
traditional medicinal plant against pathogenic bacteria. Both aqueous as well as
alcoholic extracts of the plant (root as well as leaves) were found to possess
strong antibacterial activity against a range of bacteria, as revealed by in
vitro Agar Well Diffusion Method. The methanolic extract was further
subfractionated using various solvents and the butanolic sub-fraction was found
to possess maximum inhibitory activity against a spectrum of bacteria including
Salmonella typhimurium. Moreover, in contrast to the synthetic antibiotic (viz.
chloramphenicol), these extracts did not induce lysis on incubation with human
erythrocytes, advocating their safety to the living cells. Finally, the
antibacterial efficacy of the extracts isolated from plant (both root and
leaves) was determined against experimental salmonellosis in Balb/C mice. Oral
administration of the aqueous extracts successfully obliterated salmonella
infection in Balb/C mice as revealed by increased survival rate as well as less
bacterial load in various vital organs of the treated animals.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15830846 [PubMed - indexed for MEDLINE]

57: Rejuvenation Res. 2005 Spring;8(1):37-45.

Genetically modified hairy roots of Withania somnifera Dunal: a potent source of
rejuvenating principles.

Kumar V, Murthy KN, Bhamid S, Sudha CG, Ravishankar GA.

Plant Cell Biotechnology Department, Central Food Technological Research
Institute, Mysore, Karnataka, India.

Transgenic hairy roots were induced from Withania somnifera Dunal, by infecting
leaf explants with Agrobacterium rhizogenes. Polymerase chain reaction for rol A
gene and Southern blot confirmed the integration of T-DNA in the genome.
Cultures were grown in Murashige and Skoog solid as well as in liquid medium.
The antioxidant activity was assayed in roots grown in solid media and liquid
media. Hairy roots grown in liquid media found to possess highly significant
activity in 1,1-diphenyl-2-pecryl-hydrazyl radical, beta-carotene linoleic acid
model system. The activity was 57.34%, 75.64%, and 93.41% in case DPPH model and
55.3%, 76.3%, and 90.5% in case of b-CLAMS in 25, 50, and 100 mg L(-1)
concentration, respectively. In case of hydroxyl radical trapping and brain
lipid peroxidation assay, the activity was more significant in hairy roots grown
on solid medium in comparison with commercial formulation prepared using normal
roots and standard withanaloids. Root extract grown in solid medium has shown
93.2% hydroxyl radical trapping activity at 100 mg L(-1) concentration, and 500
mg L(-1) has shown 83.6% in case of brain lipid peroxidation assay.
High-performance liquid chromatography analysis demonstrated the presence of
withanaloids in the hairy root extracts. The results of the study clearly
indicate that there is enhancement of secondary metabolites in hairy roots,
which is indicated through significant enhancement of the antioxidant activity,
since these are the major constituents responsible for the activity. This is the
first report on the presence of antioxidant principles in genetically modified
roots of W. somnifera. These results of the present study may aid in utilization
of the W. somnifera hairy roots for its rejuvenating principles.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15798373 [PubMed - indexed for MEDLINE]

58: Br J Pharmacol. 2005 Apr;144(7):961-71.

Neuritic regeneration and synaptic reconstruction induced by withanolide A.

Kuboyama T, Tohda C, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.

We investigated whether withanolide A (WL-A), isolated from the Indian herbal
drug Ashwagandha (root of Withania somnifera), could regenerate neurites and
reconstruct synapses in severely damaged neurons. We also investigated the
effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic
loss in the brain. Axons, dendrites, presynapses, and postsynapses were
visualized by immunostaining for phosphorylated neurofilament-H (NF-H),
microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic
density-95 (PSD-95), respectively. Treatment with A beta(25-35) (10 microM)
induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured
rat cortical neurons. Subsequent treatment with WL-A (1 microM) induced
significant regeneration of both axons and dendrites, in addition to the
reconstruction of pre- and postsynapses in the neurons. WL-A (10 micromol kg(-1)
day(-1), for 13 days, p.o.) recovered A beta(25-35)-induced memory deficit in
mice. At that time, the decline of axons, dendrites, and synapses in the
cerebral cortex and hippocampus was almost recovered. WL-A is therefore an
important candidate for the therapeutic treatment of neurodegenerative diseases,
as it is able to reconstruct neuronal networks.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15711595 [PubMed - indexed for MEDLINE]

59: J Ethnopharmacol. 2005 Jan 4;96(1-2):177-81.

Antimicrobial activity of some medicinal plants of the island Soqotra.

Mothana RA, Lindequist U.

Department of Pharmacognosy, Faculty of Pharmacy, Sana'a-University, PO Box
33039, Sana'a, Yemen.

Twenty-five selected plants belonging to 19 families were collected from
different localities of the island Soqotra, dried and extracted with the
solvents chloroform, methanol and hot water to yield 80 extracts. The extracts
were tested for their antimicrobial activity against several Gram-positive and
Gram-negative bacteria and against one yeast species using agar diffusion
method. Antibacterial activity was demonstrated especially against Gram-positive
bacteria including multiresistant Staphylococcus strains. The greatest activity
was exhibited by the methanolic extracts of Boswellia elongata, Boswellia
ameero, Buxus hildebrandtii, Commiphora parvifolia, Jatropha unicostata,
Kalanchoe farinacea, Pulicaria stephanocarpa, Punica protopunica, Withania
adunensis and Withania riebeckii. Only the methanolic extract of Buxus
hildebrandtii displayed significant antifungal activity.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15588668 [PubMed - indexed for MEDLINE]

60: Food Chem Toxicol. 2005 Jan;43(1):95-8.

Evaluation of the anti-genotoxicity of leaf extract of Ashwagandha.

Rani G, Kaur K, Wadhwa R, Kaul SC, Nagpal A.

Department of Botanical and Environmental Sciences, Guru Nanak Dev University,
Amritsar 143005, India.

We have undertaken the studies to investigate the presence of various activities
of the leaf extract of Ashwagandha (Lash), a commonly used shrub in Indian
traditional medicine, Ayurveda. In the present study, we studied the effect of
Lash against MNNG-induced genotoxicity in onion root tip cells. We report that
Lash offered substantial protection against the mutagenic effects of MNNG.

Publication Types:
Evaluation Studies

PMID: 15582200 [PubMed - indexed for MEDLINE]

61: Chem Pharm Bull (Tokyo). 2004 Nov;52(11):1358-61.

Cholinesterase inhibiting withanolides from Withania somnifera.

Choudhary MI, Yousuf S, Nawaz SA, Ahmed S, Atta-ur-Rahman.

H.E.J. Research Institute of Chemistry, International Center for Chemical
Sciences, University of Karachi, Karachi-75270, Pakistan. [email protected]

A total of two new (1, 2) and four known (3-6) withanolides were isolated from
the whole plant of Withania somnifera. Their structures were elucidated on the
basis of spectroscopic techniques and were characterized as
6alpha,7alpha-epoxy-3beta,5alpha,20beta-trihydroxy-1-oxowitha-24-enolide (1),
5beta,6beta-epoxy-4beta,17alpha,27-trihydroxy-1-oxowitha-2,24-dienolide (2),
withaferin-A (3), 2,3-dihydrowithaferin-A (4),
6alpha,7alpha-epoxy-5alpha,20beta-dihydroxy-1-oxowitha-2,24-dienolide (5), and
5beta,6beta-epoxy-4beta-hydroxy-1-oxowitha-2,14,24-trienolide (6), respectively.
Compounds 2, 3, 5, and 6 displayed inhibitory potential against
butyrylcholinesterase, but only compounds 3, 4, and 6 were found to be active
against acetylcholinesterase.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15520512 [PubMed - indexed for MEDLINE]

62: Angiogenesis. 2004;7(2):115-22.

Withaferin A is a potent inhibitor of angiogenesis.

Mohan R, Hammers HJ, Bargagna-Mohan P, Zhan XH, Herbstritt CJ, Ruiz A, Zhang L,
Hanson AD, Conner BP, Rougas J, Pribluda VS.

Discovery Research, EntreMed, Inc., Rockville, Maryland, USA.
[email protected]

The medicinal plant Withania somnifera is widely researched for its
anti-inflammatory, cardioactive and central nervous system effects. In Ayurveda
, the major Traditional Indian medicine system, extracts from W. somnifera are
distinctively employed for the treatment of arthritis and menstrual disorders.
Because these conditions involve angiogenic processes we hypothesized that the
W. somnifera extracts might contain angiogenesis inhibitors. We employed an
endothelial cell-sprouting assay to monitor the purification of substances from
W. somnifera root extracts and isolated as the active principle the previously
known natural product withaferin A. We show that withaferin A inhibits human
umbilical vein endothelial cell (HUVEC) sprouting in three-dimensional
collagen-I matrix at doses which are relevant to NF-kappa B-inhibitory activity.
Withaferin A inhibits cell proliferation in HUVECs (IC50 =12 nM) at doses that
are significantly lower than those required for tumor cell lines through a
process associated with inhibition of cyclin D1 expression. We propose that the
inhibition of NF-kappa B by withaferin A in HUVECs occurs by interference with
the ubiquitin-mediated proteasome pathway as suggested by the increased levels
of poly-ubiquitinated proteins. Finally, withaferin A is shown to exert potent
anti-angiogenic activity in vivo at doses that are 500-fold lower than those
previously reported to exert anti-tumor activity in vivo. In conclusion, our
findings identify a novel mode of action of withaferin A, which highlights the
potential use of this natural product for cancer treatment or prevention.

PMID: 15516832 [PubMed - indexed for MEDLINE]

63: Food Chem Toxicol. 2004 Dec;42(12):2015-20.

Evaluation of the anti-proliferative and anti-oxidative activities of leaf
extract from in vivo and in vitro raised Ashwagandha.

Kaur K, Rani G, Widodo N, Nagpal A, Taira K, Kaul SC, Wadhwa R.

Cell Proliferation Research Team, Gene Function Research Center, National
Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi,
Tsukuba, Ibaraki 305-8562, Japan.

Withania somnifera (Ashwagandha) is used in Indian traditional medicine,
Ayurveda and is believed to have a variety of health promoting effects.
Molecular mechanisms and pathways underlying these effects have not been
studied. We tried to characterize various activities of leaf extract of
Ashwagandha (Lash) raised in the field and in the laboratory. We found that the
Lash from field-raised plants has a significant anti-proliferative activity in
human tumorigenic cells. However, it did not impart any protection against the
oxidative damage caused by high glucose and hydrogen peroxide to human tumor
cells suggesting that it can be used as an anti-tumor, but not as an
anti-oxidant, substance.

PMID: 15500938 [PubMed - indexed for MEDLINE]

64: J Sep Sci. 2004 May;27(7-8):541-6.

Separation, identification, and quantification of selected withanolides in plant
extracts of Withania somnifera by HPLC-UV(DAD)--positive ion electrospray
ionisation-mass spectrometry.

Khajuria RK, Suri KA, Gupta RK, Satti NK, Amina M, Suri OP, Qazi GN.

Natural Product Chemistry Division, Regional Research Laboratory, Canal Road,
Jammu-Tawi 180001, India. [email protected]

This paper describes a method for separation, identification, and quantification
of selected withanolides in Withania somnifera plant extracts by
HPLC-UV(DAD)-Mass Spectrometry (HPLC-MS). Withaferin-A (WS-3),
12-deoxywithastramonolide (WS-12DS), Withanolide A (WS-1), and Withanone (WS-2)
were used as external standards. The compounds were isolated from Withania
somnifera by repeated column chromatography of the root extract and their
identity was established by 1H- and 13C-NMR and mass spectral data. The
compounds were chromatographed on a Merck (250 x 4.6 mm ID, 5 microm) column and
analyzed by Electrospray Ionization on a mass spectrometer in Selected Ion Mode
(SIM). For quantification, [M + Na]+ ions were monitored. Linear calibration
curves were obtained in the concentration range of 1.50 microg/mL to 6.5
microg/mL. The method was applied successfully to the detection and
quantification of the said withanolides in a number of samples.

PMID: 15335037 [PubMed - indexed for MEDLINE]

65: Phytomedicine. 2004 Jul;11(5):452-60.

The treatment of skin carcinoma, induced by UV B radiation, using 1-oxo-5beta,
6beta-epoxy-witha-2-enolide, isolated from the roots of Withania somnifera, in a
rat model.

Mathur S, Kaur P, Sharma M, Katyal A, Singh B, Tiwari M, Chandra R.

Ambedkar Centerfor Biomedical Research, University of Delhi, Delhi 110 007,
India.

Histopathological studies of the cutaneous tissues of Wistar rats exposed to UV
B radiation (294 nm) for 20 days and rats exposed to UV B radiation for 20 days,
followed by topical treatment with benzoyl peroxide, a tumor promoter (20
mg/animal/0.2 ml acetone) twice a week for 1 month, and kept under observation
for 12 weeks, demonstrate the development of malignancy. Pretreatment of the
animals with 1-oxo-5beta, 6beta-epoxy-witha-2-enolide (20 mg/kg bwt.), isolated
from the roots of Withania somnifera, prior to exposing the animals to UV B
radiation, prevents the incidence of skin carcinoma. The administration of
1-oxo-5beta, 6beta-epoxy-witha-2-enolide, to the animals after exposing them to
UV B radiation/UV B radiation and benzoyl peroxide also prevents the occurrence
of malignancy in the cutaneous tissue. Immunohistochemical staining of the
cutaneous tissues of rats exposed to UV B radiation show the presence of p53 +
foci (clusters of cells containing the mutated p53 protein), whereas an absence
of p53 + foci is observed in animals pretreated with 1-oxo-5beta,
6beta-epoxy-witha-2-enolide. These results prove that 1-oxo-5beta,
6beta-epoxy-witha-2-enolide has the potential for acting as an effective agent
to prevent the incidence of skin carcinoma induced by UV B radiation.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15330502 [PubMed - indexed for MEDLINE]

66: Altern Med Rev. 2004 Jun;9(2):211-4.

Monograph. Withania somnifera.

[No authors listed]

PMID: 15253680 [PubMed - indexed for MEDLINE]

67: J Ethnopharmacol. 2004 Aug;93(2-3):359-61.

Anticarcinogenic activity of Withania somnifera Dunal against Dalton's ascitic
lymphoma.

Christina AJ, Joseph DG, Packialakshmi M, Kothai R, Robert SJ, Chidambaranathan
N, Ramasamy M.

Division of Pharmacology, K.M. College of Pharmacy, Uthangudi, Melur Road,
Madurai 625 107, Tamil Nadu, India. [email protected]

The effect of ethanolic extract of the root of Withania somnifera Dunal (REWS)
against Dalton's Ascitic Lymphoma has been evaluated in Swiss albino mice. A
significant increase in the life span and a decrease in the cancer cell number
and tumour weight were noted in the tumour-induced mice after treatment with
REWS. The hematological parameters were also corrected by REWS in tumour-induced
mice. These observations are suggestive of the protective effect of REWS in
Dalton's Ascitic Lymphoma (DAL).

PMID: 15234777 [PubMed - indexed for MEDLINE]

68: J Ethnopharmacol. 2004 Aug;93(2-3):261-4.

Hypoglycemic activity of Withania coagulans Dunal in streptozotocin induced
diabetic rats.

Hemalatha S, Wahi AK, Singh PN, Chansouria JP.

Department of Pharmaceutics, Institute of Technology, Banaras Hindu University,
Varanasi, India. [email protected]

Administration of aqueous extract of fruits of Withania coagulans Dunal
significantly lowered the blood sugar, serum cholesterol, serum LPO, and hepatic
LPO levels at the highest concentration of 1g/kg; p.o. in streptozotocin induced
diabetic rats. In normal rats as well the blood sugar levels were significantly
decreased following treatment with the above drug. Withania coagulans also
exhibited free radical scavenging activity in an in vitro system using DPPH.

PMID: 15234762 [PubMed - indexed for MEDLINE]

69: Mol Cell Biochem. 2004 May;260(1-2):39-47.

Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a
hemodynamic, biochemical and histopathological assessment.

Gupta SK, Mohanty I, Talwar KK, Dinda A, Joshi S, Bansal P, Saxena A, Arya DS.

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi,
India. [email protected]

The efficacy of Withania somnifera (Ws) to limit myocardial injury after
ischemia and reperfusion was explored and compared to that of Vit E, a reference
standard known to reduce mortality and infarct size due to myocardial
infarction. Wistar rats (150-200 g) were divided into six groups and received
orally saline (sham, control group), Ws-50/kg (Ws control and treated group) and
Vit E-100 mg/kg (Vit E control and treated group) respectively for 1 month. On
the 31st day, rats of the control, Vit E and Ws treated groups were anesthetized
and subjected to 45 min occlusion of the LAD coronary artery followed by 60 min
reperfusion. Hemodynamic parameters: systolic, diastolic and mean arterial
pressure (SAP, DAP, MAP), heart rate (HR), left ventricular end diastolic
pressure (LVEDP), left ventricular peak (+)LVdP/dt and (-)LVdP/dt were
monitored. Hearts were removed and processed for histopathological and
biochemical studies: Myocardial enzyme viz, creatin phosphokinase (CPK), and
antioxidant parameters: malondialdehyde (MDA), glutathione (GSH), superoxide
dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) were estimated.
Postischemic reperfusion produced significant cardiac necrosis, depression of
left ventricular functions (MAP, LVEDP, (+) and (-)LVdP/dt) and a significant
fall in GSH (p < 0.01), SOD, CAT (p < 0.05), LDH and CPK (p < 0.01) as well as
an increase in MDA level (p < 0.05) in the control group rats as compared to
sham group. The changes in levels of protein and GPx was however, not
significant. Ws and Vit E favorably modulated most of the hemodynamic,
biochemical and histopathological parameters though no significant restoration
in GSH, MAP (with Vit E) were observed. Ws on chronic administration markedly
augmented antioxidants (GSH, GSHPx, SOD, CAT) while Vit E did not stimulate the
synthesis of endogenous antioxidants compared to sham. Results indicate that Ws
significantly reduced myocardial injury and emphasize the beneficial action of
Ws as a cardioprotective agent.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 15228084 [PubMed - indexed for MEDLINE]

70: Fitoterapia. 2004 Jun;75(3-4):385-8.

The in vitro antibacterial/synergistic activities of Withania somnifera
extracts.

Arora S, Dhillon S, Rani G, Nagpal A.

Department of Botanical Sciences, Guru Nanak Dev University, Amritsar 143 005,
India. [email protected]

The methanol, hexane and diethyl ether extracts from both leaves and roots of
Withania somnifera were evaluated for the antibacterial/synergistic activity by
agar plate disc-diffusion assay against Salmonella typhimurium and Escherichia
coli. Different concentrations of Tibrim, a combination of rifampicin and
isoniazid, were tested to find out the minimum inhibitory concentration (MIC),
which came out to be 0.1 mg/ml for S. typhimurium and E. coli. From the six
extracts tested, only methanol and hexane extracts of both leaves and roots were
found to have potent antibacterial activity. A synergistic increase in the
antibacterial effect of Tibrim was noticed when MIC of Tibrim was supplemented
with these extracts. Copyright 2004 Elsevier B.V.

PMID: 15159002 [PubMed - indexed for MEDLINE]

71: Int Immunopharmacol. 2004 Jun;4(6):841-9.

Immune response modulation to DPT vaccine by aqueous extract of Withania
somnifera in experimental system.

Gautam M, Diwanay SS, Gairola S, Shinde YS, Jadhav SS, Patwardhan BK.

Bioprospecting Laboratory, Interdisciplinary School of Health Sciences,
University of Pune, Pune 411007, Maharastra, India. [email protected]

Immunopotentiation on oral feeding of standardized aqueous extract of Withania
somnifera (Linn. Dunal, Family Solanaceae) was evaluated in laboratory animals
immunized with DPT (Diphtheria, Pertussis, Tetanus) vaccine. The
immunostimulation was evaluated using serological and hematological parameters.
Treatment of immunized animals with test material (100 mg/kg/day) for 15 days
resulted in significant increase of antibody titers to B. pertussis
(P=0.000007). Immunized animals (treated and untreated) were challenged with B.
pertussis 18,323 strain and the animals were observed for 14 days. Results
indicate that the treated animals did show significant increase in antibody
titers as compared to untreated animals after challenge (P=0.000003).
Immunoprotection against intracerebral challenge of live B. pertussis cells was
evaluated based on degree of sickness, paralysis and subsequent death. Reduced
mortality accompanied with overall improved health status was observed in
treated animals after intracerebral challenge of B. pertussis indicating
development of protective immune response. Present study indicates application
of the test material as potential immunopotentiating agent possible applications
in immunochemical industry. The test material also offers direct therapeutic
benefits resulting in reduced morbidity and mortality of experimental animals.
Copyright 2004 Elsevier B.V.

PMID: 15135324 [PubMed - indexed for MEDLINE]

72: J Clin Neurosci. 2004 May;11(4):397-402.

Susceptibility of hippocampus and cerebral cortex to oxidative damage in
streptozotocin treated mice: prevention by extracts of Withania somnifera and
Aloe vera.

Parihar MS, Chaudhary M, Shetty R, Hemnani T.

Biochemistry Division, Faculty of Life Science, School of Studies in Zoology,
Vikram University, Ujjain 456 010, India.

Diabetes mellitus is reported to impair the memory function in experimental
animals. Since the mammalian hippocampus and cerebral cortex play a pivotal role
in a diverse set of cognitive functions, such as novelty detection and memory,
we examined the vulnerability of cortex and hippocampus regions of the brain to
oxidative damage in streptozotocin (STZ) diabetic mice. We next examined the
attenuating effect of extracts of Withania somnifera and Aloe vera on prevention
of hippocampal and cortical cell degenerations. Doses of both plant extracts
given to experimental animals were based on the evaluation of their total
antioxidant activity and also their potency to reduce Fe(3+). We assayed lipid
peroxidation (LPO) and protein carbonyl (PC) in both regions of the brain and
observed the changes in memory and motor behavioral functions in diabetic and
control mice. The results showed a significant ( [Formula: see text] ) increase
in LPO and PC in hippocampus and cortical regions of STZ diabetic mice. We also
found a significant impairment in both motor and memory behavioral functions in
diabetic mice. However, when diabetic mice were supplemented with the extracts
of Withania somnifera and Aloe vera, the oxidative damage in both brain regions
was reduced as marked by a significant ( [Formula: see text] ) declines in both
LPO and PC. The combination of extracts of Withania somnifera and Aloe vera was
more effective in reducing oxidative damage in brain regions than the
supplementation of single plant extract. The combination also lowered the blood
glucose level in comparison to STZ diabetic mice. Memory impairment and motor
dysfunction were also improved by the plant extracts supplementation. We
conclude that impairments in the hippocampus and cortex in STZ diabetic mice are
associated with an increased free radical mediated oxidative damage and that the
supplementation of plant extracts showed preventive effects in attenuating
oxidative damage in both brain regions possibly via antioxidative mechanisms.

PMID: 15080956 [PubMed - in process]

73: Basic Clin Pharmacol Toxicol. 2004 Apr;94(4):184-90.

Mechanisms of cardioprotective effect of Withania somnifera in experimentally
induced myocardial infarction.

Mohanty I, Arya DS, Dinda A, Talwar KK, Joshi S, Gupta SK.

Department of Pharmacology, All India Instittue of Medical Sciences, New
Delhi-29, India.

The present study was designed to evaluate the cardioprotective potential of
hydro-alcoholic extract of Withania somnifera on the basis of haemodynamic,
histopathological and biochemical parameters in the isoprenaline-(isoproterenol)
induced myocardial necrosis in rats and to compare with Vitamin E, a known
cardioprotective antioxidant. Wistar albino male rats (150-200 g) were divided
into six main groups: sham, isoprenaline control, Withania somnifera/Vitamin E
control and Withania somnifera/Vitamin E treatment groups. Withania somnifera
was administered at doses 25, 50 and 100 mg/kg and Vitamin E at a dose of 100
mg/kg, orally for 4 weeks. On days 29 and 30, the rats in the isoprenaline
control and Withania somnifera/Vitamin E treatment groups were given
isoprenaline (85 mg/kg), subcutaneously at an interval of 24 hr. On day 31,
haemodynamic parameters were recorded and the hearts were subsequently removed
and processed for histopathological and biochemical studies. A significant
decrease in glutathione (P<0.05), activities of superoxide dismutase, catalase,
creatinine phosphokinase and lactate dehydrogenase (P<0.01) as well as increase
in lipid peroxidation marker malonyldialdehyde level (P<0.01) was observed in
the hearts of isoproterenol control group rats as compared to sham control.
However, we have not observed any significant changes in activity of glutathione
peroxidase and protein levels. Left ventricular dysfunction was seen as a
decrease in heart rate, left ventricular rate of peak positive and negative
pressure change and elevated left ventricular end-diastolic pressure in the
control group was recorded. On histopathological examination, myocardial damage
was further confirmed. Our data show that Withania somnifera (25, 50 and 100
mg/kg) exerts a strong cardioprotective effect in the experimental model of
isoprenaline-induced myonecrosis in rats. Augmentation of endogenous
antioxidants, maintenance of the myocardial antioxidant status and significant
restoration of most of the altered haemodynamic parameters may contribute to its
cardioprotective effect. Among the different doses studied, Withania somnifera
at 50 mg/kg dose produced maximum cardioprotective effect.

Publication Types:
Comparative Study

PMID: 15078343 [PubMed - indexed for MEDLINE]

74: Phytother Res. 2004 Feb;18(2):118-22.

Effect of Withania somnifera on B16F-10 melanoma induced metastasis in mice.

Leyon PV, Kuttan G.

Amala Cancer Research Centre, Amala Nagar Thrissur, Kerala, India.

Withania somnifera, a plant with known immunopotentiating activity and its
bioactive fraction-Withanolide D were studied for their anti-metastatic activity
using B16F-10 melanoma cells in C57BL/6 mice. Simultaneous administration of
Withania extract (122 +/- 10 tumour nodules) and Withanolide (126 +/- 9 lung
tumour nodules) could significantly (p < 0.001) inhibit the metastatic colony
formation of the melanoma in lungs. 72.58% by extract and 69.84% by Withanolide
treated, as compared to the untreated control animals also increased the
survival days. Lung collagen hydroxyproline content was highly elevated in the
control animals (23.5 +/- 0.9 micro g/mg protein), which was reduced by the
simultaneous administration of both the extract (16.3 +/- 2.0 micro g/mg
protein) and Withanolide (15.3 +/- 1.8 micro g/mg protein). The level of lung
hexosamines (4.85 +/- 0.20 mg/100 mg tissue) and uronic acids (330.1 +/- 23.7
micro g/100 mg tissue) content was also elevated in the control animals. The
elevated level of hexosamine was significantly reduced by the treatment with
extract (1.92 +/- 0.05) and Withanolide (1.85 +/- 0.05). Similarly, the uronic
acid content was also been reduced by the simultaneous administration of both
Withania extract (194.2 +/- 17.4) and Withanolide (183.2 +/- 8.8). The control
animals had 35.3 +/- 3.8 U/L gamma-glutamyl transpeptidase (gamma-GT), which was
reduced by 50% by the treatment of extract and Withanolide to 17.5 +/- 4.0 U/L
and 16.3 +/- 4.4 U/L respectively. There was a significant reduction in the
levels of sialic acid in the serum of Withania extract (60.7 +/- 7.7) and
Withanolide (67.16 +/- 5.8) treated animals compared to the higher level (102.2
+/- 8.7) in the control animals. Histopathological analysis of the lung tissues
also correlated with these findings. Prophylactic administrations of both
extract as well as Withanolide were ineffective in inhibiting the metastasis of
B16F-10 melanoma cells. Copyright 2004 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 15022162 [PubMed - indexed for MEDLINE]

75: Toxicon. 2003 Dec 15;42(8):963-77.

Natural phospholipase A(2) myotoxin inhibitor proteins from snakes, mammals and
plants.

Lizano S, Domont G, Perales J.

Facultad de Microbiologia, Instituto Clodomiro Picado, Universidad de Costa
Rica, San Jose, Costa Rica.

A renewed interest in the phenomenon of inter- and intra-species resistance
towards the toxicity of snake venoms, coupled with the search for new strategies
for treatment of snake envenomations, has prompted the discovery of proteins
which neutralize the major toxic components of these venoms. Among these
emerging groups of proteins are inhibitors of toxic phospholipases A2 (PLA2s),
many of which exhibit a wide range of toxic effects including muscle-tissue
damage, neurotoxicity, and inflammation. These proteins have been isolated from
both venomous and non-venomous snakes, mammals, and most recently from medicinal
plant extracts. The snake blood-derived inhibitors have been grouped into three
major classes, alpha, beta, and gamma, based on common structural motifs found
in other proteins with diverse physiological properties. In mammals, DM64, an
anti-myotoxic protein isolated from opossum serum, belongs to the immunoglobulin
super gene family and is homologous to human alpha1B-glycoprotein and DM43, a
metalloproteinase inhibitor from the same organism. In plants, a short note is
made of WSG, a newly described anti-toxic-PLA2 glycoprotein isolated from
Withania somnifera (Ashwaganda), a medicinal plant whose aqueous extracts
neutralize the PLA2 activity of the Naja naja venom. The implications of these
new groups of PLA2 toxin inhibitors in the context of our current understanding
of snake biology as well as in the development of novel therapeutic reagents in
the treatment of snake envenomations worldwide are discussed.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15019494 [PubMed - indexed for MEDLINE]

76: J Altern Complement Med. 2003 Dec;9(6):897-907.

Effect of 1-oxo-5beta, 6beta-epoxy-witha-2-ene-27-ethoxy-olide isolated from the
roots of Withania somnifera on stress indices in Wistar rats.

Kaur P, Sharma M, Mathur S, Tiwari M, Divekar HM, Kumar R, Srivastava KK,
Chandra R.

Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi
110-007, India. [email protected]

OBJECTIVE: Isolation of biologically active fractions and compounds from the
roots of Withania somnifera, a plant used extensively as a constituent of
rasayana, in Ayurveda and to test their adaptogenic activity on stress indices
using the cold-hypoxia-restraint (C-H-R) model. DESIGN: Bioactivity-guided
fractionation of an aqueous extract of the roots of Withania somnifera led to
the isolation of a new species of withanolide 1-oxo-5beta,
6beta-epoxy-witha-2-ene-27-ethoxy-olide. Structure elucidation, was carried out
using proton nuclear magnetic resonance, infrared (IR), ultraviolet (UV), and
mass spectroscopic analysis. Stress-related indices were evaluated, namely serum
creatine phosphokinase (CPK) activity, serum lactate dehydrogenase (LDH)
activity, serum corticosterone levels, and serum lipid peroxidation (LPO)
levels. RESULTS: There was a significant decrease in a serum CPK, LDH, and LPO
levels in animals pretreated with (1) fraction-I (20 mg/kg body weight), (2)
1-oxo-5beta, 6beta-epoxy-witha-2-ene-27-ethoxy-olide (2.5 mg/kg body weight) in
comparison to control when subjected to C-H-R stress. CONCLUSIONS: The results
show that the a new species of withanolide, 1-oxo-5beta,
6beta-epoxy-witha-2-ene-27-ethoxy-olide (compound-1) could prove to be an
effective agent to counteract C-H-R stress.

PMID: 14736361 [PubMed - indexed for MEDLINE]

77: J Ethnopharmacol. 2004 Jan;90(1):49-55.

Immunoprotection by botanical drugs in cancer chemotherapy.

Diwanay S, Chitre D, Patwardhan B.

Department of Microbiology, Abasaheb Garware College, Pune, India.

Most of the synthetic chemotherapeutic agents available today are
immunosuppressants, cytotoxic, and exert variety of side effects that are
particularly evident in cancer chemotherapy. Botanical based immunomodulators
are often employed as supportive or adjuvant therapy to overcome the undesired
effects of cytotoxic chemotherapeutic agents and to restore normal health. Total
extract, polar and non-polar extracts, and their formulations, prepared from
medicinal plants mentioned in Ayurveda, namely, Withania somnifera (Linn Dunal)
(Solanaceae), Tinospora cordifolia (Miers) (Menispermaceae), and Asparagus
racemosus (Willd.) (Liliaceae), exhibited various immunopharmacological
activities in cyclophosphamide (CP)-treated mouse ascitic sarcoma. Treatment of
ascitic sarcoma-bearing mice with a formulation of total extracts of Withania
somnifera and Tinospora cordifolia (80:20) and alkaloid-free polar fraction of
Withania somnifera resulted in protection towards CP-induced myelo- and
immunoprotection as evident by significant increase in white cell counts and
hemagglutinating and hemolytic antibody titers. Treatment with these candidate
drugs will be important in development of supportive treatment with cancer
chemotherapy.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14698508 [PubMed - indexed for MEDLINE]

78: Drug Metabol Drug Interact. 2003;19(3):211-22.

Withania somnifera (Ashwagandha) attenuates antioxidant defense in aged spinal
cord and inhibits copper induced lipid peroxidation and protein oxidative
modifications.

Gupta SK, Dua A, Vohra BP.

Department of Zoology, Kurukshetra University, Haryana, India.

Withania somnifera is classified in Ayurveda, the ancient Indian system of
medicine, as a rasayana, a group of plant-derived drugs which promote physical
and mental health, augment resistance of the body against disease and diverse
adverse environmental factors, revitalize the body in debilitated conditions and
increase longevity. We investigated the effects of Withania somnifera on
copper-induced lipid peroxidation and antioxidant enzymes in aging spinal cord
of Wistar rats. The activity of glutathione peroxidase (GPx) decreased
significantly in the spinal cord from adult to aged mice. Treatment with
Withania somnifera successfully attenuated GPx activity and inhibited lipid
peroxidation in a dose dependent manner. Withania somnifera inhibited both the
lipid peroxidation and protein oxidative modification induced by copper. These
effects were similar to those of superoxide dismutase and mannitol. The results
indicate the therapeutic potential of Withania somnifera in aging and
copper-induced pathophysiological conditions.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14682611 [PubMed - indexed for MEDLINE]

79: Life Sci. 2003 Nov 21;74(1):125-32.

Growth inhibition of human tumor cell lines by withanolides from Withania
somnifera leaves.

Jayaprakasam B, Zhang Y, Seeram NP, Nair MG.

Bioactive Natural Products and Phytoceuticals, Department of Horticulture and
National Food Safety and Toxicology Center, Michigan State University, East
Lansing, MI 48824, USA.

Ayurvedic medicines prepared in India consist of Withania somnifera roots as one
of the main ingredients. It is consumed as a dietary supplement around the
world. The leaves of W. somnifera were used in the treatment of tumors and
inflammation in several Asian countries. We have isolated twelve withanolides
such as withaferin A (1), sitoindoside IX (2), 4-(1-hydroxy-2,
2-dimethylcyclpropanone)-2, 3-dihydrowithaferin A (3), 2, 3-dihydrowithaferin A
(4), 24, 25-dihydro-27-desoxywithaferin A (5), physagulin D
(1-->6)-beta-D-glucopyranosyl- (1-->4)-beta-D-glucopyranoside (6),
27-O-beta-D-glucopyranosylphysagulin D (7), physagulin D (8), withanoside IV
(9), and 27-O-beta-D-glucopyranosylviscosalactone B (10), 4, 16-dihydroxy-5beta,
6beta-epoxyphysagulin D (11), viscosalactone B (12) from the leaves of this
species. Compounds 1-12 and diacetylwithaferin A (13) were tested for their
antiproliferative activity on NCI-H460 (Lung), HCT-116 (Colon), SF-268 (Central
Nervous System; CNS and MCF-7 (Breast) human tumor cell lines. The inhibitory
concentration to afford 50% cell viability (IC50) for these compounds was
determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide)
assay. Withaferin A and its derivatives exhibited inhibitory concentrations
(50%) ranging from 0.24 +/- 0.01 to 11.6 +/- 1.9 microg/mL. Viscosalactone B
(12) showed the 50% inhibition at concentrations ranging from 0.32 +/- 0.05 to
0.47 +/- 0.15 microg/mL whereas its 27-O-glucoside derivative (10) exhibited
IC50 between 7.9 +/- 2.9 and 17.3 +/- 3.9 microg/ml. However, Physagulin D type
withanolides showed either weak or no activity at 30 microg/mL. Therefore,
incorporation of withanolides in the diet may prevent or decrease the growth of
tumors in human.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 14575818 [PubMed - indexed for MEDLINE]

80: Phytomedicine. 2003;10(6-7):474-82.

Antiatherogenic effect of Caps HT2, a herbal Ayurvedic medicine formulation.

Mary NK, Babu BH, Padikkala J.

Amala Cancer Research Centre, Thrissur, Kerala, India.

The antiatherogenic effect of a herbal formulation, Caps HT2, was evaluated as
antioxidant, anticoagulant, platelet antiaggregatory, lipoprotein lipase
releasing, anti-inflammatory and hypolipidaemic activity in rats. The
formulation contained the methanolic extracts of selected parts of plants,
Commiphora mukul, Allium sativum, Plumbago indica, Semecarpus anacardium,
Hemidesmus indicus, Terminalia arjuna, Tinospora cordifolia, Withania somnifera
and Ocimum sanctum. The formulation, Caps HT2 was found to scavenge superoxide
and hydroxyl radicals; the IC50 required being 55.0 and 610.0 microg/ml
respectively. The lipid peroxidation was found inhibited (50%) by 48.5 microg/ml
of Caps HT2. The intravenous administration of the formulation (5 mg/kg) delayed
the plasma recalcification time in rabbits and enhanced the release of
lipoprotein lipase enzyme significantly (p < 0.001). The formulation also
inhibited ADP induced platelet aggregation in vitro, which was comparable to
commercial heparin. The anti-inflammatory action of the formulation was
significant (p < 0.001) with acute and chronic inflammations induced by
carrageenan and formalin respectively in rats. The hypolipidaemic effect of Caps
HT2 was significant (p < 0.001) with the administration of the formulation, in
diet-induced hyperlipidaemia of rats for a period of 30 days. Oral
administration of the formulation, Caps HT2 (100, 200, 300 and 400 mg/kg)
significantly raised HDL cholesterol levels. The atherogenic index and the
reduction in body weight were significant indicating the effectiveness against
hyperlipidaemia and obesity. All these results revealed the therapeutic
potential of Caps HT2 against vascular intimal damage and atherogenesis leading
to various types of cardiovascular problems.

PMID: 13678230 [PubMed - indexed for MEDLINE]

81: J Med Food. 2003 Summer;6(2):107-14.

Effect of Withania somnifera root extract on haloperidol-induced orofacial
dyskinesia: possible mechanisms of action.

Naidu PS, Singh A, Kulkarni SK.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab
University, Chandigarh-160014, India.

We investigated the role of oxidative stress in the pathophysiology of
haloperidol (HP)-induced orofacial dyskinesia and evaluated the beneficial
effect of Withania somnifera (Ws) root extract in the amelioration of HP-induced
vacuous chewing movements (VCMs) and tongue protrusions in the rat model for TD.
Rats were treated for 21 days with intraperitoneal HP (1 mg/kg); on day 22, VCMs
and tongue protrusions were counted during a 5-minute observation period.
HP-treated rats significantly developed these extrapyramidal symptoms, but
coadministration of Ws root extract (100-300 mg/kg) dose-dependently reduced
them. Biochemical analysis revealed that chronic HP treatment significantly
increased lipid peroxidation and decreased forebrain levels of glutathione and
the antioxidant defense enzymes, superoxide dismutase (SOD) and catalase.
Coadministration of Ws extract significantly reduced the lipid peroxidation and
significantly reversed the decrease in forebrain SOD and catalase levels but had
no significant effect on the HP-induced decrease in forebrain glutathione
levels. These findings strongly suggest that oxidative stress plays a
significant role in HP-induced orofacial dyskinesia and that Ws could be
effective in preventing neuroleptic-induced extrapyramidal side effects.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12935321 [PubMed - indexed for MEDLINE]

82: Pharmacol Biochem Behav. 2003 Jun;75(3):547-55.

Adaptogenic activity of Withania somnifera: an experimental study using a rat
model of chronic stress.

Bhattacharya SK, Muruganandam AV.

Department of Pharmacology, Postgraduate Institute of Basic Medical Sciences,
Calcutta University, 244 B Acharya JC Bose Road, Calcutta 700 020, India.

Withania somnifera (WS) Dunal is classified in Ayurveda, the ancient Hindu
system of medicine, as a rasayana, a group of plant-derived drugs reputed to
promote physical and mental health, augment resistance of the body against
disease and diverse adverse environmental factors, revitalise the body in
debilitated conditions and increase longevity. These attributes are remarkably
similar to the properties ascribed to adaptogens like Panax ginseng (PG) in
contemporary medicine. As such, the adaptogenic activity of a standardised
extract of WS roots was investigated against a rat model of chronic stress (CS).
The stress procedure was mild, unpredictable footshock, administered once daily
for 21 days to adult male Wistar rats. CS induced significant hyperglycaemia,
glucose intolerance, increase in plasma corticosterone levels, gastric
ulcerations, male sexual dysfunction, cognitive deficits, immunosuppression and
mental depression. These CS induced perturbations were attenuated by WS (25 and
50 mg/kg po) and by PG (100 mg/kg po), administered 1 h before footshock for 21
days. The results indicate that WS, like PG, has significant antistress
adaptogenic activity, confirming the clinical use of the plant in Ayurveda.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12895672 [PubMed - indexed for MEDLINE]

83: Clin Exp Pharmacol Physiol. 2003 May-Jun;30(5-6):399-404.

Evaluation of Withania somnifera in a middle cerebral artery occlusion model of
stroke in rats.

Chaudhary G, Sharma U, Jagannathan NR, Gupta YK.

Departments of Pharmacology and NMR, All India Institute of Medical Sciences,
New Delhi, India.

1. Stroke causes brain injury in millions of people worldwide each year. Despite
the enormity of the problem, there is currently no approved therapy that can
reduce infarct size or neurological disability. One of the approaches that can
be used in limiting the neurological damage after stroke is the use of
prophylactic treatment in patients with a high-risk of stroke. The present study
was undertaken to investigate the effect of the Indian herbal plant Withania
somnifera as a prophylactic treatment in the middle cerebral artery (MCA)
occlusion model of stroke in rats. 2. Two groups of male Wistar rats were
pretreated with a hydroalcoholic extract of W. somnifera (1 g/kg, p.o.) for 15
and 30 days. Thereafter, rats were subjected to focal ischaemia by occlusion of
the MCA using an intraluminal thread. After 2 h MCA occlusion, reperfusion was
allowed by retracting the thread. Animals were assessed for ischaemic changes
using diffusion-weighted imaging 30 min after reperfusion. Twenty-four hours
later, rats were subjected to motor performance tests and were subsequently
killed for the estimation of the marker of oxidative stress malondialdehyde
(MDA). The control group received vehicle and a similar protocol was followed.
3. Significant motor impairment, with elevated levels of MDA, was observed in
vehicle-treated MCA-occluded rats. In addition, diffusion-weighted imaging
showed increased signal intensity in the right hemisphere compared with the
contralateral hemisphere. Treatment with W. somnifera for 15 days did not
improve motor performance or decrease the elevated levels of MDA. However, when
the pretreatment time of W. somnifera was increased to 30 days, it prevented
motor impairment and significantly decreased the raised levels of MDA compared
with vehicle-treated rats. In the W. somnifera (30 days)-pretreated group, the
percentage hemispheric lesion area in diffusion-weighted imaging was
significantly attenuated (17 +/- 2%) compared with the vehicle-treated
MCA-occluded group (30 +/- 4%). 4. Because W. somnifera has been documented to
have anti-oxidant properties, the protection afforded by W. somnifera could be
due to its anti-oxidant effect. The present study provides first evidence of the
effectiveness of an Indian herb in focal ischaemia.

Publication Types:
Comparative Study

PMID: 12859433 [PubMed - indexed for MEDLINE]

84: Phytochemistry. 2003 Jun;63(4):387-90.

Withanolides from Withania coagulans.

ur-Rahman A, Dur-e-Shahwar, Naz A, Choudhary MI.

H.E.J. Research Institute of Chemistry, International Center for Chemical
Sciences, University of Karachi, Karachi-75270, Pakistan.

Two withanolides, 20beta-hydroxy-1-oxo-(22R)-witha-2,5,24-trienolide (1) and
withacoagulin (2), along with a known withanolide, 17beta-hydroxy-14alpha,
20alpha-epoxy-1-oxo-(22R)-witha-3,5,24-trienolide (3) were isolated from
Withania coagulans. Their structures were elucidated with the help of different
spectroscopic techniques.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12770585 [PubMed - indexed for MEDLINE]

85: Phytother Res. 2003 May;17(5):531-6.

Adaptogenic activity of a novel withanolide-free aqueous fraction from the roots
of Withania somnifera Dun. (Part II).

Singh B, Chandan BK, Gupta DK.

Department of Pharmacology, Regional Research Laboratory, Canal Road Jammu-Tawi
180 016, India. [email protected]

In the Indian traditional system of medicine Withania somnifera Dun. is widely
regarded as the Indian Ginseng. A new withanolide-free hydrosoluble fraction was
isolated from the roots of Withania somnifera Dun. and was evaluated for
putative antistress activity against a battery of tests to delineate the
activity of this fraction. The latter fraction exhibited significant antistress
activity in a dose-related manner (Singh et al., 2001) and was further studied
against chemical and physical induced stress in rats and mice. The extract of
Withania somnifera root (a commercial preparation available locally) was also
used to compare the results. A preliminary acute toxicity study in mice showed a
good margin of safety with a high therapeutic index. Copyright 2003 John Wiley &
Sons, Ltd.

PMID: 12748992 [PubMed - indexed for MEDLINE]

86: Phytother Res. 2003 Apr;17(4):306-10.

Protective effect of a polyherbal formulation (Immu-21) against
cyclophosphamide-induced mutagenicity in mice.

Jena GB, Nemmani KV, Kaul CL, Ramarao P.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical
Education and Research, Sector-67, S A S Nagar, Punjab 160 062, India.

The object was to evaluate the effects of a polyherbal formulation, Immu-21,
against cyclophosphamide (CP)-induced chromosomal aberrations (CA) and
micronuclei (MN) in mice. CP alone (40 mg/kg, i.p.) produced classical as well
as non-classical chromosomal aberrations in mice, and the incidence of CA was
significantly more in the CP treated group when compared with that of the
control group. Immu-21, which contains extracts of Ocimum sanctum, Withania
somnifera, Emblica officinalis and Tinospora cordifolia, was given at 100 mg/kg,
daily, over 7 days, and 30 mg/kg daily over 14 days and inhibited both
CP-induced classical and non-classical chromosomal aberrations ( approximately
40%-60% of control). A significant increase in MN was also observed in bone
marrow erythrocytes of mice treated with CP, and pretreatment with Immu-21 also
significantly reduced these. Cytotoxicity was evaluated by estimating the ratio
of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs). The
present results indicate that chronic treatment with Immu-21 prevented
CP-induced genotoxicity in mice. Copyright 2003 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12722129 [PubMed - indexed for MEDLINE]

87: Drugs R D. 2003;4(2):103-9.

Evaluation of the antiretroviral activity of a new polyherbal drug (Immu-25) in
patients with HIV infection.

Usha PR, Naidu MU, Raju YS.

Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of
Medical Sciences, Hyderabad, India. [email protected]

OBJECTIVE: To evaluate the clinical efficacy and safety of a new polyherbal
preparation, Immu-25, in HIV-infected patients. METHODS: 36 patients (10 female,
26 male) with a mean age of 35 +/-10 years, with confirmed HIV infection with a
CD4 count <500 cells/microL, received two capsules of the test drug twice daily
for 18 months in this open-label pilot study. Patients were evaluated at monthly
intervals for general signs and symptoms, development of opportunistic
infections, and changes in weight and performance index. Lymphocyte phenotyping
and routine haematological, biochemical, hepatic and renal parameters were
recorded after every 6 months of drug therapy. Viral load was evaluated before
and after every 6 months of treatment. RESULTS: The polyherbal test preparation
produced good symptomatic improvement within 6 months. There was an increase in
mean (95% CI) weight from 58 (53-64)kg to 63 (56-69)kg, 64 (58-72)kg and 68
(62-74)kg after 6, 12 and 18 months of treatment, respectively. The incidence
and severity of symptoms such as diarrhoea, fatigue, anorexia, cough and fever
decreased with drug treatment. There was a decrease in the mean (95% CI) viral
load from 326 438 (428 600-186 420) copies/mL to 180 495 (258 300-124 000)
copies/mL and 22 069 (42 100-16 000) copies/mL after 6 and 12 months of
treatment, respectively. The decrease in viral load was associated with an
increase in mean (95% CI) CD4 count from a baseline of 243 (203-388)
cells/microL to 336 (263-486) cells/microL after 6 months of therapy, and this
continued to rise to 527 (285-767) cells/microL (p < 0.001) and 618 (362-1012)
cells/microL (p < 0.001) after 12 and 18 months of treatment, respectively. With
the exception of mild gastrointestinal adverse effects, the drug was well
tolerated. Both patients and investigators rated the treatment as good or very
good. CONCLUSION: The polyherbal drug Immu-25 showed a favourable effect in
patients with HIV infection. The test drug decreased the mean viral load, which
was associated with good symptomatic improvement and an increase in the mean CD4
cell count. On the basis of these data, it can be concluded that this herbal
drug may have a good immunomodulatory effect and has potential as a
co-therapeutic agent in the management of HIV infection. Further studies are
warranted to confirm its therapeutic potential.

PMID: 12718564 [PubMed - indexed for MEDLINE]

88: Indian J Exp Biol. 2002 Oct;40(10):1161-3.

Effect of poly herbal formulation, EuMil, on neurochemical perturbations induced
by chronic stress.

Bhattacharya A, Muruganandam AV, Kumar V, Bhattacharya SK.

Neuropharmacology Laboratory, Department of Pharmacology, Institute of Medical
Sciences, Banaras Hindu University, Varanasi 221 005, India.

EuMil, a polyherbal formulation consisting of standardised extracts of Withania
somnifera (L) Dunal, Ocimum sanctum L, Asparagus racemosus Wilid and Emblica
officinalis Gaertn., is used as an anti-stress agent to attenuate the various
aspects of stress related disorders. In the present study, the neurochemical
mechanisms underlying the anti-stress activity of EuMil were evaluated by
measuring the rat brain monoamine neurotransmitter levels and tribulin activity.
Chronic electroshock stress (14 days) significantly decreased the nor-adrenaline
(NA) and dopamine (DA) levels in frontal Cortex, pons-medulla, hypothalamus,
hippocampus and striatal, hypothalamal region, respectively, and increased the
5-hydroxytryptamine (5HT) level in frontal cortex, pons medulla, hypothalamus
and hippocampus. Chronic stress, also increased the rat brain tribulin activity.
EuMil (100 mg/kg, p.o., 14 days) treatment normalized the perturbed regional NA,
DA, 5HT concentrations, induced by chronic stress. EuMil also significantly
attenuated the stress-induced increase in the rat brain tribulin activity. The
amelioration of chronic stress-induced neurochemical perturbations by EuMil
explains the neurochemical mechanisms underlying the observed putative
anti-stress activity of the product.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12693697 [PubMed - indexed for MEDLINE]

89: Indian J Exp Biol. 2002 Oct;40(10):1151-60.

Effect of poly herbal formulation, EuMil, on chronic stress-induced homeostatic
perturbations in rats.

Muruganandam AV, Kumar V, Bhattacharya SK.

R & D Centre, Indian Herbs Ltd., Saharanpur 247 001, India. [email protected]

EuMil, is a herbal formulation comprising the standardised extracts of Withania
somnifera (L) Dunal, Ocimum sanctum L, Asparagus racemosus Willd and Emblica
officinalis Gaertn., all of which are classified in Ayurveda as rasayanas to
promote physical and mental health, improve defense mechanisms of the body and
enhance longevity. These attributes are similar to the modern concept of
adaptogenic agents, which are, known to afford protection to the human
physiological system against diverse stressors. The present study was undertaken
to investigate the adaptogenic and antistress activity of EuMil against chronic
unpredictable, but mild, footshock stress-induced perturbations in behaviour
(depression), glucose metabolism, suppressed male sexual behaviour,
immunosuppression and cognitive dysfunction in CF strain albino rats. Panex
ginseng (PG) was used for comparison. Gastric ulceration, plasma corticosterone
levels, serum lipid, hepatic and renal functions were used as the stress
indices. These effects were attenuated by EuMil (dose 100 mg/kg, p.o.) and PG
(100 mg/kg. p.o.), administered once daily over a period of 14 days, the period
of stress induction period. Further, chronic stress also induced glucose
intolerance, suppressed male sexual behaviour, induced behavioural despair and
cognitive dysfunction and immunosuppression. All these chronic stress-induced
perturbations were attenuated, in a dose dependent manner by EuMil and PG. Thus,
the results indicate that EuMil has significant adaptogenic and anti-stress,
activity, qualitatively comparable to PG, against a variety of behavioural,
biochemical and physiological perturbations, induced by unpredictable stress,
which has been proposed to be a better indicator of clinical stress than acute
stress. The likely contribution of the individual constituents of EuMil in the
observed adaptogenic action of the polyherbal formulation, has been discussed.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12693696 [PubMed - indexed for MEDLINE]

90: J Biosci. 2003 Feb;28(1):121-8.

Phenolic antioxidants attenuate hippocampal neuronal cell damage against kainic
acid induced excitotoxicity.

Parihar MS, Hemnani T.

Biochemistry Division, Faculty of Life Science, School of Studies in Zoology,
Vikram University, Ujjain 456 010, India. [email protected]

Increasing evidence supports the role of excitotoxicity in neuronal cell injury.
Thus, it is extremely important to explore methods to retard or reverse
excitotoxic neuronal injury. In this regard, certain dietary compounds are
beginning to receive increased attention, in particular those involving
phytochemicals found in medicinal plants in alleviating neuronal injury. In the
present study, we examined whether medicinal plant extracts protect neurons
against excitotoxic lesions induced by kainic acid (KA) in female Swiss albino
mice. Mice were anesthetized with ketamine and xylazine (200 mg and 2 mg/kg body
wt. respectively) and KA (0.25 microg in a volume of 0.5 microl) was
administered to mice by intra hippocampal injections. The results showed an
impairment of the hippocampus region of brain after KA injection. The lipid
peroxidation and protein carbonyl content were significantly (P < 0.05)
increased in comparison to controls. Glutathione peroxidase (GPx) activity (EC
1.11.1.9) and reduced glutathione (GSH) content declined after appearance of
excitotoxic lesions. As GPx and GSH represent a major pathway in the cell for
metabolizing hydrogen peroxide (H2O2), their depletion would be expected to
allow H2O2 to accumulate to toxic levels. Dried ethanolic plant extracts of
Withania somnifera (WS), Convolvulus pleuricauas (CP) and Aloe vera (AV)
dissolved in distilled water were tested for their total antioxidant activity.
The diet was prepared in terms of total antioxidant activity of plant extracts.
The iron (Fe3+) reducing activity of plant extracts was also tested and it was
found that WS and AV were potent reductants of Fe3+ at pH 5 5. CP had lower Fe3+
reducing activity in comparison to WS and AV. Plant extracts given singly and in
combination 3 weeks prior to KA injections resulted in a decrease in
neurotoxicity. Measures of lipid peroxidation and protein carbonyl declined. GPx
activity and GSH content were elevated in hippocampus supplemented with WS and
combination of WS + CP + AV. However, when CP and AV were given alone, the
changes in the GPx activity and GSH content were not significant. Although the
major factors involved in these properties of phytochemicals remain to be
specified, the finding of this study has suggested that phytochemicals present
in plant extracts mitigate the effects of excitotoxicity and oxidative damage in
hippocampus and this might be accomplished by their antioxidative properties.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 12682435 [PubMed - indexed for MEDLINE]

91: J Ethnopharmacol. 2003 May;86(1):113-6.

Lens aldose reductase inhibiting potential of some indigenous plants.

Halder N, Joshi S, Gupta SK.

Department of Pharmacology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi 110029, India.

Cataract is the leading cause of blindness worldover. Diabetes is one of the
major risk factors for cataractogenesis and aldose reductase (AR) has been
reported to play an important role in sugar-induced cataract. In the present
study, the AR inhibitory activity of Ocimum sanctum (OS), Withania somnifera
(WS), Curcuma longa (CL), Azadirachta indica (AI) were studied together with
their effect on sugar-induced cataractogenic changes in rat lenses in vitro.
Aqueous extracts of the plants, procured from Dabur, India, were reconstituted
with double distilled water to make various dilutions. AR inhibitory activity of
these extracts and their anticataract potentials were evaluated in vitro in rat
lenses. AR inhibitory activity of the aqueous extract of different plants was
calculated considering the AR activity of normal rat lenses as 100%. The
concentration of the plant extract that showed maximum AR inhibitory activity
was selected to further study its effect on galactose-induced lens swelling and
polyol accumulation in vitro. All the four plants were found to inhibit lens AR
activity but to different extent. From dose-response curve, OS was found to be
the most effective AR inhibitor followed by CL, AI and WS. The IC(50) values of
OS, CL, AI and WS were calculated to be 20, 55, 57 and 89 microg/ml,
respectively. OS showed a significant inhibition (38.05%) in polyol accumulation
followed by CL and AI (28.4 and 25.04%, respectively). WS did not show any
effect on polyol level in rat lenses. None of the plant extracts showed any
significant effect on lens water content.OS possesses a significant anticataract
activity in vitro and its anticataract potential could be related with its AR
inhibitory effect.

PMID: 12686449 [PubMed - indexed for MEDLINE]

92: J Med Food. 2002 Winter;5(4):211-20.

Effect of natural and synthetic antioxidants in a mouse model of chronic fatigue
syndrome.

Singh A, Naidu PS, Gupta S, Kulkarni SK.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab
University, Chandigarh 160014, India.

Chronic fatigue syndrome (CFS) is an illness characterized by persistent and
relapsing fatigue, often accompanied by numerous symptoms involving various body
systems. The etiology of CFS remains unclear; however, a number of studies have
shown that oxidative stress may be involved in its pathogenesis. In the present
study, a mouse model of CFS was used in which mice were forced to swim for one
6-minute session on each day for 15 days and the immobility period was recorded.
There was a significant increase in immobility period in saline-treated mice on
successive days. Intraperitoneal treatment with the potent antioxidants
carvedilol (5 mg/kg) and melatonin (5 mg/kg) produced a significant reduction in
immobility period. Similar results were observed with herbal preparations
administered orally: Withania somnifera (100 mg/kg), quercetin (50 mg/kg), and
St. John's wort (Hypericum perforatum L., 10 mg/kg). Biochemical analysis
revealed that chronic swimming significantly induced lipid peroxidation and
decreased glutathione (GSH) levels in the brains of mice. The rats also showed
decreased levels of antioxidant defense enzymes, superoxide dismutase (SOD), and
catalase. Co-administration of antioxidants carvedilol, melatonin, W. somnifera,
quercetin or St. John's wort significantly reduced lipid peroxidation and
restored the GSH levels decreased by chronic swimming in mice. Further, the
treatment increased levels of SOD in the forebrain and of catalase. The findings
strongly suggest that oxidative stress plays a significant role in the
pathophysiology of CFS and that antioxidants could be useful in the treatment of
CFS.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12639396 [PubMed - indexed for MEDLINE]

93: J Exp Clin Cancer Res. 2002 Dec;21(4):585-90.

Effect of Withania somnifera on cell mediated immune responses in mice.

Davis L, Kuttan G.

Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.

Effect of Withania somnifera on the cellular immune responses (CMI) was studied
in normal as well as tumour bearing animals. Administration of Withania extract
was found to enhance the proliferation of lymphocytes, bone marrow cells and
thymocytes in responses to mitogens. Both PHA and Con A mitogens along with
Withania treated splenocytes, bone marrow cells and thymocytes could stimulate
proliferation twice greater than the normal. Withania treated splenocytes along
with the mitogen LPS (10 microg/ml) could stimulate the lymphocyte proliferation
six times more than the normal. Natural killer cell activity (NK) was found to
be enhanced significantly in both the normal and the tumour bearing group and it
was found to be earlier than the control (48.92% cell lysis). Antibody dependent
cellular cytotoxicity (ADCC) was found to be enhanced in the Withania treated
group on the 9th day (65% cell lysis). An early Antibody dependent complement
mediated cytotoxicity (ACC) was observed in the Withania treated group on day 13
(47% cell lysis).

PMID: 12636106 [PubMed - indexed for MEDLINE]

94: Indian J Exp Biol. 2002 Mar;40(3):282-7.

Cell proliferation and natural killer cell activity by polyherbal formulation,
Immu-21 in mice.

Nemmani KV, Jena GB, Dey CS, Kaul CL, Ramarao P.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical
Education and Research, Sector-67, S. A. S. Nagar 160 062, India.

Immunomodulatory activity of an Ayurvedic polyherbal formulation, Immu-21
containing extracts of Ocimum sanctum, Withania somnifera, Emblica officinalis
and Tinospora cordifolia was studied on proliferative response of splenic
leukocytes to T cell mitogens, concanavalin (Con)-A and phytohemagglutinin (PHA)
and B cell mitogen, lipopolysaccharide (LPS) in vitro by [3H]-thymidine uptake
assay in mice. The cytotoxic activity of Immu-21 was tested by measuring the
splenic leukocyte natural killer (NK) cell activity against K 562 cells.
Intraperitoneal (i.p.) treatment with Immu-21 (30 mg/kg) once a day for 14 and
21 days did not cause change in body weight and spleen weight, where as
splenocytes/spleen count was increased. Treatment of Immu-21 (30 mg/kg, i.p.)
for 14 days and 1 mg/kg for 21 days significantly increased LPS induced
leukocyte proliferation. NK cell activity was significantly increased when mice
were pretreated with Immu-21 (10 and 30 mg/kg, i.p.) once a day for 7 days. The
results indicate that pretreatment with Immu-21 selectively increased the
proliferation of splenic leukocyte to B cell mitogen, LPS and cytotoxic activity
against K 562 cells in mice.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12635697 [PubMed - indexed for MEDLINE]

95: Fitoterapia. 2003 Feb;74(1-2):68-76.

Quantitative HPLC analysis of withanolides in Withania somnifera.

Ganzera M, Choudhary MI, Khan IA.

Department of Pharmacognosy, University of Innsbruck, Innsbruck 6020, Austria.
[email protected]

One of the most widely used herbs in Ayurvedic medicine is Ashwaghanda, Withania
somnifera, a shrub commonly found on the Indian subcontinent. As this plant is
increasingly becoming a popular adaptogenic in the western world, analytical
methods for its identification and quality control are in demand. Thus, a HPLC
method for the determination of withaferin A and withanolide D was developed.
The system was successfully used to investigate the presence of the markers in
different W. somnifera plant parts as well as to analyze their content in market
products.

Publication Types:
Evaluation Studies
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 12628397 [PubMed - indexed for MEDLINE]

96: Electrophoresis. 2003 Jan;24(3):336-42.

Analysis of selected withanolides in plant extract by capillary
electrochromatography and microemulsion electrokinetic chromatography.

Cherkaoui S, Cahours X, Veuthey JL.

Laboratory of Pharmaceutical Analytical Chemistry, University of Geneva, Geneva,
Switzerland.

Microemulsion electrokinetic chromatography (MEEKC) coupled with a diode-array
detector was developed for the simultaneous analysis of natural steroidal
compounds, withanolides including withaferin A, withacnistin and iochromolide.
Optimal resolution was obtained with a microemulsion consisting of 70 mM octane,
800 mM 1-butanol, 100 mM sodium dodecyl sulfate (SDS), and 10 mM
phosphate-borate buffer (pH 7) using a fused-silica capillary at 25 kV and 40
degrees C. Since this technique is not compatible with mass spectrometry
detection, a capillary electrochromatographic method was developed to separate
the investigated withanolides. The effects of mobile phase composition and pH
were systematically investigated. Complete separation was obtained with a
capillary electrochromatography (CEC) Hypersil C18 bonded silica column (packed
length, 25 cmx100 microm ID and 375 microm OD), packed with 3 microm particles.
The mobile phase consisted of formic acid-ammonia, pH 8 / acetonitrile (40/60
v/v); the voltage was set at 25 kV and the temperature at 20 degrees C. Under
these conditions, resolution of these closely related compounds, including the
critical pair withacnistin and iochromolide, was achieved in less than 5 min.
The separations by MEEKC and CEC were compared with that obtained by
reversed-phase liquid chromatography and showed similar retention order,
indicating the analogy of the retention mechanism of these techniques. To
further improve specificity and sensitivity, the developed CEC method was
interfaced with electrospray ionization mass spectrometry using a Teflon
connection between the CEC column and a void fused-silica capillary. Finally,
the described methods were applied to the qualitative analysis of withanolides
in Iochroma gesnerioides plant extract.

PMID: 12569525 [PubMed - indexed for MEDLINE]

97: Life Sci. 2003 Feb 21;72(14):1617-25.

Induction of nitric oxide synthase expression by Withania somnifera in
macrophages.

Iuvone T, Esposito G, Capasso F, Izzo AA.

Department of Experimental Pharmacology, University of Naples Federico II, via
D. Montesano 49, 80131, Naples, Italy.

Withania somnifera (ashwagandha, Indian ginseng) is an immunostimulant herbal
medicine used to improve overall health and prevent diseases, particularly in
the elderly. However, the mechanisms underlying its immunostimulant effect is
poorly understood. To elucidate the mechanism of Withania somnifera, we
investigated the effect of a methanolic extract from the root of Withania
somnifera (WS) on nitric oxide (NO) production in J774 macrophages. We found
that WS (1-256 microg/ml) produced a significant and concentration-dependent
increase in NO production, an effect which was abolished by N(G)nitro-L-arginine
methyl ester (L-NAME, 3-300 microM), a non-selective inhibitor of NO synthase
(NOS), dexamethasone (10 microM), an inhibitor of protein synthesis and
N(alpha-p)-tosyl-L-lysine chloromethyl ketone (TLCK, 0.01-10 microM), an
inhibitor of nuclear factor-kappaB (NF-kappaB) activation. Dexamethasone did not
have any effect on NO production once NOS had been induced (i.e. 12 h after WS).
Moreover, western blot analysis showed that WS increased, in a
concentration-dependent fashion, inducible NOS protein expression. These results
demonstrate that WS may induce the synthesis of inducible NOS expression likely
by acting at transcriptional level. The increased NO production by macrophages
could account, at least in part, for the immunostimulant properties of Withania
somnifera.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12551750 [PubMed - indexed for MEDLINE]

98: Asian J Androl. 2002 Dec;4(4):295-8.

Effect of Withania somnifera root extract on the sexual behaviour of male rats.

Ilayperuma I, Ratnasooriya WD, Weerasooriya TR.

Department of Anatomy, Faculty of Medicine, University of Ruhuna, Sri Lanka.

AIM: To determine the effect of a methanolic extract of Withania somnifera (L.)
Dunal roots on sexual competence of male rats. METHODS: Male rats were orally
administered 3000 mg.kg-1.day-1 of root extract for 7 days. Their sexual
behaviour was evaluated 7 days prior to treatment, day 3 and 7 of treatment, and
day 7, 14 and 30 post-treatment by pairing each male with a receptive female.
RESULTS: The root extract induced a marked impairment in libido, sexual
performance, sexual vigour, and penile erectile dysfunction. These effects were
partly reversible on cessation of treatment. These antimasculine effects are not
due to changes in testosterone levels or toxicity but may be attributed to
hyperprolactinemic, GABAergic, serotonergic or sedative activities of the
extract. CONCLUSION: Use of W. somnifera roots may be detrimental to male sexual
competence.

PMID: 12508132 [PubMed - indexed for MEDLINE]

99: Arch Biochem Biophys. 2002 Dec 1;408(1):42-50.

Purification and characterization of a glycoprotein inhibitor of toxic
phospholipase from Withania somnifera.

Deepa M, Veerabasappa Gowda T.

Department of Studies in Biochemistry, University of Mysore, Manasagangothri,
570 006, Mysore, India.

A phospholipase inhibitor (WSG) has been purified from Withania somnifera using
gel-filtration and ion-exchange chromatographies. The WSG is an acidic
glycoprotein. Its molecular mass as determined by SDS-PAGE was 27kDa. It
neutralized the enzyme activity and pharmacological properties such as
cytotoxicity, edema, and myotoxicity of a multi-toxic Indian cobra venom
phospholipase (NNXIa-PLA) but failed to neutralize the neurotoxicity. The glycan
part of the molecule does not appear to be involved in any of the
pharmacological properties studied. The results suggest that the neutralization
of the pharmacological effects of the toxic phospholipase is brought about by
inhibition of the enzyme activity by formation of a complex between the WSG and
the toxic phospholipase. We report the purification and characterization of a
glycoprotein phospholipase A inhibitor from Withania somnifera, medicinal plant.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12485601 [PubMed - indexed for MEDLINE]

100: Neuroreport. 2002 Oct 7;13(14):1715-20.

Axon- or dendrite-predominant outgrowth induced by constituents from
Ashwagandha.

Kuboyama T, Tohda C, Zhao J, Nakamura N, Hattori M, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, Toyama, Japan.

We previously reported that the methanol extract of Ashwagandha (roots of Dunal)
induced dendrite extension in a human neuroblastoma cell line. In this study, we
found that six of the 18 compounds isolated from the methanol extract enhanced
neurite outgrowth in human neuroblastoma SH-SY5Y cells. Double immunostaining
was performed in rat cortical neurons using antibodies to phosphorylated NF-H as
an axonal marker, and to MAP2 as a dendritic marker. In withanolide A-treated
cells, the length of NF-H-positive processes was significantly increased
compared with vehicle-treated cells, whereas, the length of MAP2-positive
processes was increased by withanosides IV and VI. These results suggest that
axons are predominantly extended by withanolide A, and dendrites by withanosides
IV and VI. Copyright 2002 Lippincott Williams & Wilkins

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 12395110 [PubMed - indexed for MEDLINE]

101: Nutr Cancer. 2002;42(1):91-7.

Withania somnifera root extract prevents DMBA-induced squamous cell carcinoma of
skin in Swiss albino mice.

Prakash J, Gupta SK, Dinda AK.

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi
110029, India.

The chemopreventive effect of Withania somnifera hydroalcoholic root extract
(WSRE) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer was
investigated in Swiss albino mice. The skin lesions were induced by the
twice-weekly topical application of DMBA (100 nmol/ 100 microliters acetone) for
8 wk on the shaved back of mice. WSRE was administered at the maximal tolerated
dose of 400 mg/kg p.o. three times per week on alternate days 1 wk before DMBA
and continued for 24 wk thereafter. The results of the study revealed a
significant decrease in incidence and average number of skin lesions in mice
compared with DMBA alone at the end of Week 24. Biochemical parameters were
assessed in the lesions of WSRE-treated and untreated control mice. A
significant impairment was noticed in the levels of reduced glutathione,
malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, and
glutathione S-transferase in skin lesions of DMBA-treated control mice compared
with vehicle-treated mice. These parameters were returned to near normal by
administration of WSRE to DMBA-treated mice. The above findings were supported
by histopathological studies. From the present study, it can be inferred that
WRSE possesses potential chemopreventive activity in this experimental model of
cancer. The chemopreventive activity may be linked to the antioxidant/free
radical-scavenging constituents of the extract. The anti-inflammatory and
immunomodulatory properties of WSRE are also likely to contribute to its
chemopreventive action.

PMID: 12235655 [PubMed - indexed for MEDLINE]

102: Altern Ther Health Med. 2002 Sep-Oct;8(5):18-9.

Effects of ashwagandha in a rat model of stroke.

Adams JD Jr, Yang J, Mishra LC, Singh BB.

Publication Types:
Letter

PMID: 12233797 [PubMed - indexed for MEDLINE]

103: Arch Pharm (Weinheim). 2002 Jun;335(6):267-76.

New withanolides and other constituents from the fruit of Withania somnifera.

Abou-Douh AM.

Department of Chemistry, Faculty of Science, South Valley University, Aswan,
Egypt. [email protected]

Two new steroidal lactones of the withanolide-type, 5beta, 6alpha, 14alpha,
17beta, 20beta-pentahydroxy-1-oxo-20 S, 22R-witha-2, 24-dienolide (1)and 6alpha,
7alpha-epoxy-5alpha, 14alpha, 17alpha, 23beta-tetrahydroxy-1-oxo-22R-witha-2,
24-dienolide (2), were isolated from the fruit of Withania somnifera (L.) Dunal
(Solanaceae) growing in Southern Egypt, together with two known coumarins,
scopoletin (3)and aesculetin (4), a known triterpene, viz. Beta-amyrin (5), and
two known phytosterols, viz. stigmasterol (6) and sitosterol (7). The structures
of the isolated compounds have been elucidated by spectroscopic methods
including UV, IR, (1)H-, (13)C-NMR, DEPT experiments, HRFAB-, FAB-, and EI-mass
spectrometry. The in vitro antimicrobial activity of the new withanolide (1) and
the alcoholic fruit extract are discussed.

PMID: 12210769 [PubMed - indexed for MEDLINE]

104: J Exp Clin Cancer Res. 2002 Mar;21(1):115-8.

Effect of Withania somnifera on CTL activity.

Davis L, Kuttan G.

Amala Cancer Research Centre, Amala Nagar, Thrissur, India.

The stimulatory effect of Withania somnifera on cytotoxic T lymphocytes was
determined in Balb/C mice by the Winn's Neutralization assay using CTL sensitive
EL4 thymoma cells as target cells. Withania somnifera showed a significant
increase in CTL production both in vivo as well as in vitro. The survival time
of E14 cells alone in treated animals was only 21 days and in the Withania
extract treated group was 45 days with a percentage increase in life span (%
ILS) of 114.28%. The survival rate of animals administered with EL4 cells
(target) which were incubated with alloimmunized spleen cells (effector) from
normal Balb/c mice was 33 days (% ILS 57.14%) and when this group was treated
with Withania extract (20 mg/dose/animal i.p. for 10 days) their life span was
increased to 53 days (% ILS 152.38%). The survival days of animals after the
administration of EL4 cells incubated with alloimmunized spleen cells (effector)
from Withania treated animals was 48 days (% ILS 118.18%) and when these animals
continued with the Withania treatment their life span increased to 61 days (%ILS
177.27%). There was a significant increase in life span when animals were
treated with EL4 cells incubated with effector cells generated by mixed
lymphocyte culture of Balb/c mice and C57BL/6 mice in the presence (172.73%) and
absence of Withania extract (59.09%). These studies indicate that Withania
somnifera could stimulate the generation of cytotoxic T lymphocyte and it may
reduce tumour growth.

Publication Types:
In Vitro

PMID: 12071516 [PubMed - indexed for MEDLINE]

105: Chem Pharm Bull (Tokyo). 2002 Jun;50(6):760-5.

Withanolide derivatives from the roots of Withania somnifera and their neurite
outgrowth activities.

Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K.

Department of Metabolic Engineering, Toyama Medical and Pharmaceutical
University, Sugitani, Japan.

Five new withanolide derivatives (1, 9-12) were isolated from the roots of
Withania somnifera together with fourteen known compounds (2-8, 13-19). On the
basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were
determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5
beta,27-trihydroxy-1-oxowitha-24-enolide (1),
27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl
(1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D-glucopyranosyl
(1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranosyl
(1-->6)-beta-D-glucopyranoside (withanoside IX, 10),
27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside
X, 11), and (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide
3-O-beta-D-glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1,
withanolide A (2), (20S,22R)-4 beta,5 beta,6
alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide (6), withanoside IV (14),
withanoside VI (15) and coagulin Q (16) showed significant neurite outgrowth
activity at a concentration of 1 microM on a human neuroblastoma SH-SY5Y cell
line.

PMID: 12045329 [PubMed - indexed for MEDLINE]

106: Phytomedicine. 2002 Mar;9(2):167-70.

Effect of Withania somnifera glycowithanolides on a rat model of tardive
dyskinesia.

Bhattacharya SK, Bhattacharya D, Sairam K, Ghosal S.

Withania somnifera glycowithanolides (WSG) were investigated for their
preventive effect on the animal model of tardive dyskinesia (TD), induced by
once daily administration of the neuroleptic, haloperidol (1.5 mg/kg, i.p.), for
28 days. Involuntary orofacial movements (chewing movements, tongue protusion
and buccal tremors) were assessed as TD parameters. WSG (100 and 200 mg, p.o.),
administered concomitantly with haloperidol for 28 days, inhibited the induction
of the neuroleptic TD. Haloperidol-induced TD was also attenuated by the
antioxidant, vitamin E (400 and 800 mg/kg, p.o.), but remained unaffected by the
GABA-mimetic antiepileptic agent, sodium valproate (200 and 400 mg/kg, p.o.),
both agents being administered for 28 days like WSG. The results indicate that
the reported antioxidant effect of WSG, rather than its GABA-mimetic action, may
be responsible for the prevention of haloperidol-induced TD.

Publication Types:
Letter

PMID: 11995951 [PubMed - indexed for MEDLINE]

107: Indian J Exp Biol. 2001 Oct;39(10):1068-70.

Clastogenic effects of dietary supplement--Spirulina alga, and some medicinal
plant products from Boswellia serrata, Withania somnifera on mice.

Ghoshal S, Mukhopadhyay MJ, Mukherjee A.

Centre of Advanced Study in Cell and Chromosome Research, Department of Botany,
University of Calcutta, Kolkata, India.

Pretreatment of aqueous extracts of Zyrulina (Spirulina), Aswagandha (Withania)
and Nopane (Boswellia) on colchicine induced chromosome damage showed weakness
of clastogenic activity in Swiss albino mice. None of the treatments increased
significantly the number of chromosome aberrations.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11883518 [PubMed - indexed for MEDLINE]

108: Phytomedicine. 2001 Nov;8(6):492-4.

Downregulation of p34cdc2 expression with aqueous fraction from Withania
somnifera for a possible molecular mechanism of anti-tumor and other
pharmacological effects.

Singh DD, Dey CS, Bhutani KK.

Publication Types:
Letter

PMID: 11824528 [PubMed - indexed for MEDLINE]

109: Microbiol Res. 2001;156(4):303-9.

Microorganisms asssociated with Withania somnifera leaves.

Alwadi HM, Baka ZA.

Department of Biology, Faculty of Science, King Khalid University, Abha, P.O.
Box 9004, Saudi Arabia.

Microorganisms including bacteria, actinomycetes and fungi were recovered from
the leaves of Withania somnifera, which were collected from two altitudinal
ranges (0-300 m and 1700-2000 m) in the Asir region, Saudi Arabia. Types and
numbers of microorganisms varied according to the altitude and the month of
collection. The number of microorganisms was higher on old leaves than that on
young ones in most cases. Low altitude exhibited more microorganisms than high
altitude. The relationship between meteorological factors and type and number of
the recovered microorganisms is discussed. Inoculation of detached healthy
leaves of Withania by all recovered fungal species revealed only Alternaria
solani as a pathogen of this plant. To confirm pathogenicity, scanning and
transmission electron microscopic examination revealed the colonization of this
pathogen inside the leaf tissue. Penetration of Withania leaves by the fungus
occurred only through stomata, and the invading hyphae were located in the
intercellular spaces of leaf tissues. Ultrastructural changes noted in infected
cells included changes in chloroplasts and the invagination of the host plasma
membrane.

PMID: 11770847 [PubMed - indexed for MEDLINE]

110: Phytochemistry. 2001 Oct;58(3):455-62.

Calystegine distribution in some solanaceous species.

Bekkouche K, Daali Y, Cherkaoui S, Veuthey JL, Christen P.

Laboratory of Medicinal Plants and Phytochemistry, Department of Biology,
Faculty of Sciences-Semlalia, PO Box 2390, Marrakech, Morocco.

The distribution of eight calystegines (A(3), A(5), B(1), B(2), B(3), B(4), C(1)
and N(1)) and their content was investigated by gas chromatography coupled to
mass spectrometry (GC-MS) in Datura metel, Atropa belladonna, Hyoscyamus albus,
Mandragora autumnalis, Solanum sodomaeum, Withania somnifera, Withania
frutescens and Brunfelsia nitida. The most frequently encountered calystegines
were A(3), B(1), B(2) and B(3), while distribution of N(1) and C(1) was more
limited. In all the investigated samples, calystegines A(5) and B(4) were never
detected. This report focuses for the first time on calystegines in Withania and
Brunfelsia genera and in Mandragora autumnalis and Solanum sodomaeum species.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11557078 [PubMed - indexed for MEDLINE]

111: Phytother Res. 2001 Sep;15(6):544-8.

Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions
of female albino rat.

Jain S, Shukla SD, Sharma K, Bhatnagar M.

Department of Zoology, University College of Science, M.L. Sukhadia University,
Udaipur 313001, India.

The neuroprotective effects of W. somnifera were studied on stressed adult
female Swiss albino rats. Experimental rats were subjected to immobilization
stress for 14 h and were treated with a root powder extract of W. somnifera
available as Stresscom capsules (Dabur India Ltd). Control rats were maintained
in completely, non stressed conditions. Thionin stained serial coronal sections
(7 microm) of brain passing through the hippocampal region of stressed rats
(E(1) group) demonstrated 85% degenerating cells (dark cells and pyknotic cells)
in the CA(2) and CA(3) sub-areas. Treatment with W. somnifera root powder
extract significantly reduced (80%) the number of degenerating cells in both the
areas. The study thus demonstrates the antistress neuroprotective effects of W.
somnifera. Copyright 2001 John Wiley & Sons, Ltd.

PMID: 11536389 [PubMed - indexed for MEDLINE]

112: Phytother Res. 2001 Sep;15(6):524-8.

Nootropic-like effect of ashwagandha (Withania somnifera L.) in mice.

Dhuley JN.

Laboratory Pharmacology and Toxicology, Research Centre, Hindustan Antibiotics
Ltd, Pimpri, Pune 411 018, India. [email protected]

Ashwagandha (Withania somnifera L.) root extract (50, 100 and 200 mg/kg; orally)
improved retention of a passive avoidance task in a step-down paradigm in mice.
Ashwagandha (50, 100 and 200 mg/kg; orally) also reversed the scopolamine (0.3
mg/kg)-induced disruption of acquisition and retention and attenuated the
amnesia produced by acute treatment with electroconvulsive shock (ECS),
immediately after training. Chronic treatment with ECS, for 6 successive days at
24 h intervals, disrupted memory consolidation on day 7. Daily administration of
ashwagandha for 6 days significantly improved memory consolidation in mice
receiving chronic ECS treatment. Ashwagandha, administered on day 7, also
attenuated the disruption of memory consolidation produced by chronic treatment
with ECS. On the elevated plus-maze, ashwagandha reversed the scopolamine (0.3
mg/kg)-induced delay in transfer latency on day 1. On the basis of these
findings, it is suggested that ashwagandha exhibits a nootropic-like effect in
naive and amnesic mice. Copyright 2001 John Wiley & Sons, Ltd.

PMID: 11536383 [PubMed - indexed for MEDLINE]

113: Phytomedicine. 2001 Jul;8(4):283-91.

Adaptogenic activity of a glyco-peptido-lipid fraction from the alcoholic
extract of Trichopus zeylanicus Gaertn.

Singh B, Gupta DK, Chandan BK.

Department of Pharmacology, Regional Research Laboratory, Jammu-Tawi, India.
[email protected]

A glyco-peptido lipid fraction ("AF") from the alcoholic extract of Trichopus
zeylanicus Gaertn. was evaluated for putative antistress activity in a battery
of tests. "AF" exhibited significant antistress activity in dose dependent
manner in all the parameters studied, against the different stresses use to
induce non-specific stress. Ashwagandha, the commercial extract of Withania
somnifera roots was used as control: A preliminary acute toxicity study in mice
showed a good margin of safety, as the ALD50 value was more than 3000 mg/kg body
wt. p.o. with no signs of abnormalities.

PMID: 11515718 [PubMed - indexed for MEDLINE]

114: Planta Med. 2001 Jul;67(5):432-6.

Production of withaferin A in shoot cultures of Withania somnifera.

Ray S, Jha S.

Centre of Advanced Study, Department of Botany, Calcutta University, India.

Multiple shoot cultures of Withania somnifera were established from single shoot
tip explants and their potential for the production of two principle
withanolides, withaferin A and withanolide D was investigated. Shoot tips grown
on MS medium supplemented with BA (1 mg l(-1)) induced 10.0 +/- 1.15 microshoots
per explants and shoot cultures accumulated both withanolides (withaferin A =
0.04%, withanolide D = 0.06%). Supplementation of MSSM (solid) agar medium with
4% sucrose enhanced accumulation of both withaferin A (0.16%) and withanolide D
(0.08%). Reduction of the agar concentration to 0.16% increased the number of
microshoots induced per explant to 25.5. MSSM liquid medium containing 10%
coconut milk favoured a maximum increase in biomass (27 fold); number of
microshoots induced (37.6 +/- 1.45) as well as accumulation of withaferin A
(0.14%).

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11488457 [PubMed - indexed for MEDLINE]

115: Indian J Physiol Pharmacol. 2001 Apr;45(2):253-7.

Reversal of paclitaxel induced neutropenia by Withania somnifera in mice.

Gupta YK, Sharma SS, Rai K, Katiyar CK.

Department of Pharmacology, All India Institute of Medical Sciences, New
Delhi-110 029.

The effect of aqueous extract of Withania somnifera (L. Solanaceae) was studied
against paclitaxel induced neutropenia in mice. After paclitaxel 1 mg/kg, i.v.
administration significant fall in total WBC and absolute neutrophil count was
observed on day 3 and day 5. W. Somnifera (200 mg/kg, p.o.) per se produced
significant increase in neutrophil counts. W. somnifera (200 mg/kg, p.o.) when
administered for 4 days before paclitaxel treatment and continued for 12 days
caused significant reversal of neutropenia of paclitaxel. The findings of the
study suggest the potential of W. somnifera as an adjuvant during cancer
chemotherapy for the prevention of bone marrow depression associated with
anticancer drugs.

PMID: 11480235 [PubMed - indexed for MEDLINE]

116: Bioorg Med Chem. 2001 Jun;9(6):1499-507.

Structures of withanosides I, II, III, IV, V, VI, and VII, new withanolide
glycosides, from the roots of Indian Withania somnifera DUNAL. and inhibitory
activity for tachyphylaxis to clonidine in isolated guinea-pig ileum.

Matsuda H, Murakami T, Kishi A, Yoshikawa M.

Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Kyoto,
Japan

Seven new withanolide glycosides called withanosides I, II, III, IV, V, VI, and
VII were isolated from an Indian natural medicine, Ashwagandha, the roots of
Indian Withania somnifera DUNAL. (Solanaceae), together with four known
compounds, withaferin A, 5 alpha,20 alpha(F)(R)-dihydroxy-6 alpha,7
alpha-epoxy-1-oxowitha-2,24-dienolide, physagulin D, and coagulin Q. The
structures of withanosides I, II, III, IV, V, VI, and VII were determined based
on chemical and physicochemical evidence. Principal constituents, withanoside VI
(10 and 30 microM) and withaferin A (10 microM), attenuated the tachyphylaxis to
clonidine on electrically stimulated guinea-pig ileum in vitro.

Publication Types:
In Vitro

PMID: 11408168 [PubMed - indexed for MEDLINE]

117: Phytother Res. 2001 Jun;15(4):311-8.

Adaptogenic activity of a novel, withanolide-free aqueous fraction from the
roots of Withania somnifera Dun.

Singh B, Saxena AK, Chandan BK, Gupta DK, Bhutani KK, Anand KK.

Departments of Pharmacology and Natural Products Chemistry, Regional Research
Laboratory, Canal Road, Jammu--Tawi 180 001, India. [email protected]

The practitioners of the traditional Indian system of medicine regard Withania
somnifera Dun. as the 'Indian ginseng'. A new withanolide-free aqueous fraction
was isolated from the roots of this plant and was evaluated for putative
antistress activity against a battery of tests such as hypoxia time, antifatigue
effect, swimming performance time, swimming induced gastric ulceration and
hypothermia, immobilization induced gastric ulceration, autoanalgesia and
biochemical changes in the adrenal glands. This bioactive fraction exhibited
significant antistress activity in a dose-related manner in all the parameters
studied. The extract of Withania somnifera root (a commercial preparation
available locally) was used to compare the results. A preliminary acute toxicity
study in mice showed a good margin of safety. Copyright 2001 John Wiley & Sons,
Ltd.

PMID: 11406854 [PubMed - indexed for MEDLINE]

118: Phytother Res. 2001 May;15(3):240-4.

Chemopreventive activity of Withania somnifera in experimentally induced
fibrosarcoma tumours in Swiss albino mice.

Prakash J, Gupta SK, Kochupillai V, Singh N, Gupta YK, Joshi S.

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi -
110029, India.

The current experimental work deals with the chemopreventive studies of a
hydroalcoholic extract of Withania somnifera roots, against
20-methylcholanthrene induced fibrosarcoma tumours in Swiss albino mice. A
single subcutaneous injection of 200 microg 20-methylcholanthrene in 0.1 mL of
dimethylsulphoxide into the thigh region of mice produced a high incidence (96%)
of tumours. Oral treatment of animals with 400 mg/kg body weight of Withania
somnifera extract (one week before injecting 20-methylcholanthrene and continued
until 15 weeks thereafter) significantly reduced the tumour incidence, tumour
volume and enhanced the survival of the mice, compared with
20-methylcholanthrene injected mice. The tumour incidence was also delayed in
the treatment group when compared with 20-methylcholanthrene injected mice.
Liver biochemical parameters revealed a significant modulation of reduced
glutathione, lipid peroxides, glutathione-S-transferase, catalase and superoxide
dismutase in extract treated mice compared with 20-methylcholanthrene injected
mice. The mechanism of chemopreventive activity of Withania somnifera extract
may be due to its antioxidant and detoxifying properties. Copyright 2001 John
Wiley & Sons, Ltd.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11351360 [PubMed - indexed for MEDLINE]

119: Indian J Exp Biol. 2000 Oct;38(10):1007-13.

Stress induced neuron degeneration and protective effects of Semecarpus
anacardium Linn. and Withania somnifera Dunn. in hippocampus of albino rats: an
ultrastructural study.

Shukla SD, Jain S, Sharma K, Bhatnagar M.

Department of Zoology, M.L.S. University, Udaipur 313 001, India.

Effects of herbal formulations were studied on hippocampal neuron cell bodies.
Study was carried out in adult Swiss albino rats. Experimental rats (E) were
divided into three groups. Group E1 rats were given immobilization stress for 14
hr/day for 30 days. Rats in E2 and E3 group were given daily single dose (40
mg/kg/body wt.) of alcoholic extract of S. anacardium and W. somnifera. After 1
hr giving the plant extract, the rats were subjected to stress. Treatment
continued for 14 hr for 30 days. Control rats were kept in complete nonstress
condition. Ultrastructural characteristics of neuron cell bodies in hippocampal
sublayer (CA1-CA4 and Dg) was studied in rats of E1, E2 and E3 groups and
compared with control. Results of the present study demonstrated, that both CA2
and Dg, 85% of neuron cell bodies exhibited degenerating characteristics, (which
includes karyorrhexis, membrane blebbing, chromatin condensation, chromatin
fragmentation and intracellular spacing). Interestingly, after the treatment
with S. ancardium cells demonstrating degenerating characteristics was
significantly reduced (80%) as compared to treatment with W. somnifera. Study
suggests that probably both the herbal drugs have cytoprotective properties.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11324152 [PubMed - indexed for MEDLINE]

120: Phytomedicine. 2001 Mar;8(2):125-32.

Indian medicinal plants as antiradicals and DNA cleavage protectors.

Russo A, Izzo AA, Cardile V, Borrelli F, Vanella A.

Department of Biochemistry, Medical Chemistry and Molecular Biology, University
of Catania, Italy. [email protected]

Celastrus paniculatus L. (Celastraceae) (CP), Picrorhiza kurroa L.
(Scrophulariaceae) (PK) and Withania somnifera L. (Solanaceae) (WS) are Indian
medicinal plants having a remarkable reputation, as a factor of health care,
among the indigenous medical practitioners. The plants exhibit varying degrees
of therapeutic value some of which useful in the treatment of cognitive
dysfunction, epilepsy, insomnia, rheumatism, gout, dyspepsia. In this work, we
have investigated the free radical scavenging capacity of methanolic extracts
from CP, PK, WS and the effect on DNA cleavage induced by H2O2 UV-photholysis.
In addition, we investigated whether these plant extracts are capable of
reducing the hydrogen peroxide-induced cytotoxicity and DNA damage in human
non-immortalized fibroblasts. These extracts showed a dose-dependent free
radical scavenging capacity and a protective effect on DNA cleavage; methanolic
extracts from PK was more active than extracts from CP and WS. These results
were confirmed by a significant protective effect on H2O2-induced cytoxicity and
DNA damage in human non-immortalized fibroblasts. These antioxidant effects of
active principle of CP, PK and WS may explain, at least in part, the reported
anti-stress, immunomodulatory, cognition-facilitating, anti-inflammatory and
antiaging effects produced by them in experimental animal and in clinical
situations and may justify the further investigation of their other beneficial
biological properties.

PMID: 11315755 [PubMed - indexed for MEDLINE]

121: Planta Med. 2001 Mar;67(2):146-9.

In vitro propagation of Withania somnifera and isolation of withanolides with
immunosuppressive activity.

Furmanowa M, Gajdzis-Kuls D, Ruszkowska J, Czarnocki Z, Obidoska G, Sadowska A,
Rani R, Upadhyay SN.

Department of Biology and Pharmaceutical Botany, Medical University of Warsaw,
Warsaw, Poland.

Withania somnifera plantlets were produced in vitro from the shoot-tip of
aseptically germinated seedlings. Culture conditions were optimized using
different plant growth regulators which gave rise to 120 shoots from a single
bud. The plantlets were then transferred to pots and maintained in greenhouse
for 4 months. 90% of these in vitro propagated plantlets survived and showed
normal growth. Leaves from these plants were used for isolation of the
withanolides. Methanolic extract of leaves from plantlets growing in tissue
culture and those transferred to the greenhouse were evaluated for
immunomodulatory activity. While the extract from greenhouse samples showed
potent immunosuppressive activity, those from tissue cultures samples did not
show any activity. Fractionation and characterization of withanolides, using
HPLC, NMR, MS methods revealed the presence of withaferin A in the greenhouse
samples. Our results indicate that Withania species may require longer time and
better differentiation and also natural environment for the production of
withaferin A.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11301861 [PubMed - indexed for MEDLINE]

122: J Ethnopharmacol. 2001 May;75(2-3):165-8.

Effect of Withania somnifera on DMBA induced carcinogenesis.

Davis L, Kuttan G.

Amalanagar Cancer Research Centre, Amalanagar, Thrissur, 680 553, Kerala, India.

Administration of an extract of Withania somnifera was found to reduce two stage
skin carcinogenesis induced by DMBA (dimethyl benzanthracene) and croton oil.
Withania somnifera was administered at a concentration of (20 mg/dose/animal
i.p.) consecutively on 5 days prior to DMBA administration and continued twice
weekly for 10 weeks. After the 180th day of carcinogen administration, all of
the animals developed papilloma in the control group whereas only six out of 12
animals developed papilloma in the treated group. A total of 11 papillomas were
found in the control group while only six developed them in the Withania
somnifera treated group. Enzyme analysis of skin and liver showed significant
enhancement in antioxidant enzymes such as GSH, GST, Glutathione peroxides and
Catalases in Withania somnifera treated group when compared with the control.
The elevated level of lipid peroxide in the control group was significantly
inhibited by Withania somnifera administration. These studies indicate that
Withania somnifera could reduce the papilloma induced alterations to the
antioxidant defense systems.

PMID: 11297845 [PubMed - indexed for MEDLINE]

123: J Ethnopharmacol. 2001 Apr;75(1):1-4.

The effect of aqueous extracts of Cynomorium coccineum and Withania somnifera on
testicular development in immature Wistar rats.

Abdel-Magied EM, Abdel-Rahman HA, Harraz FM.

Department of Veterinary Medicine, King Saud University, P.O. Box 1482,
Buraidah, Saudi Arabia.

The effect of lyophilized aqueous extract of Cynomorium coccineum and Withania
somnifera on testicular development and on serum levels of testosterone, ICSH
and FSH was studied in immature male Wistar rats. There was a notable increase
in testicular weight of animals treated with both extracts. Histological
examination revealed an apparent increase in the diameter of seminiferous
tubules and the number of seminiferous tubular cell layers in the testes of
treated rats as compared with control ones. Extracts of both plants elicited
notable spermatogenesis in immature rats but C. coccineum was more effective
than W. somnifera in that respect. Serum testosterone and FSH levels were lower
in animals treated with plants extracts than controls, whereas ICSH levels was
higher in treated animals, specially in those treated with C. coccineum. It was
concluded that extracts of both plants have a direct spermatogenic influence on
the seminiferous tubules of immature rats presumably by exerting a
testosterone-like effect.

PMID: 11282435 [PubMed - indexed for MEDLINE]

124: Fitoterapia. 2001 Feb;72(2):179-81.

Effect of certain plant extracts on alpha-amylase activity.

Prashanth D, Padmaja R, Samiulla DS.

Bioassay unit, Research & Development Centre, Natural Remedies Pvt. Ltd., Plot
No. 5B, Veerasandra Indl. Area, Hosur Road, -561 229, Bangalore, India.
[email protected]

Ethanolic extracts of Punica granatum, Mangifera indica, Boerhaavia diffusa,
Embelia ribes, Phyllanthus maderaspatensis, and Withania somnifera, were tested
for their effect on alpha-amylase activity (in vitro). P. granatum and M. indica
were found to exhibit interesting alpha-amylase inhibitory activity.

PMID: 11223231 [PubMed - indexed for MEDLINE]

125: Indian J Exp Biol. 2000 Feb;38(2):119-28.

Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic
rasayanas.

Bhattacharya SK, Bhattacharya A, Chakrabarti A.

Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
University, Varanasi 221 005, India.

Siotone (ST) is a herbal formulation comprising of Withania somnifera, Ocimum
sanctum, Asparagus racemosus, Tribulus terristris and shilajit, all of which are
classified in Ayurveda as rasayanas which are reputed to promote physical and
mental health, improve defence mechanisms of the body and enhance longevity.
These attributes are similar to the modern concept of adaptogenic agents, which
are, known to afford protection of the human physiological system against
diverse stressors. The present study was undertaken to investigate the
adaptogenic activity of ST against chronic unpredictable, but mild, footshock
stress induced perturbations in behaviour (depression), glucose metabolism,
suppressed male sexual behaviour, immunosuppression and cognitive dysfunction in
CF strain albino rats. Gastric ulceration, adrenal gland and spleen weights,
ascorbic acid and corticosterone concentrations of adrenal cortex, and plasma
corticosterone levels, were used as the stress indices. Panax ginseng (PG) was
used as the standard adaptogenic agent for comparison. Additionally, rat brain
levels of tribulin, an endogenous endocoid postulated to be involved in stress,
were also assessed in terms of endogenous monoamine oxidase (MAO) A and MAOB
inhibitory activity. Chronic unpredictable footshock induced marked gastric
ulceration, significant increase in adrenal gland weight and plasma
corticosterone levels, with concomitant decreases in spleen weight, and
concentrations of adrenal gland ascorbic acid and corticosterone. These effects
were attenuated by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.),
administered once daily over a period of 14 days, the period of stress
induction. Chronic stress also induced glucose intolerance, suppressed male
sexual behaviour, induced behavioural depression (Porsolt's swim despair test
and learned helplessness test) and cognitive dysfunction (attenuated retention
of learning in active and passive avoidance tests), and immunosuppression
(leucocyte migration inhibition and sheep RBC challenged increase in paw oedema
in sensitized rats). All these chronic stress-induced perturbations were
attenuated, dose-dependently by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg,
p.o.). Chronic stress-induced increase in rat brain tribulin activity was also
reversed by these doses of ST and by PG. The results indicate that ST has
significant adaptogenic activity, qualitatively comparable to PG, against a
variety of behavioural, biochemical and physiological perturbations induced by
unpredictable stress, which has been proposed to be a better indicator of
clinical stress than acute stress parameters. The likely contribution of the
individual constituents of ST in the observed adaptogenic action of the
polyherbal formulation, have been discussed.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11218827 [PubMed - indexed for MEDLINE]

126: Genome. 2000 Dec;43(6):975-80.

Genetic variation and relationship among and within Withania species as revealed
by AFLP markers.

Negi MS, Singh A, Lakshmikumaran M.

Bioresources and Biotechnology Division, Tata Energy Research Institute, New
Delhi, India.

Withania somnifera is an important medicinal plant, and its anticancerous
properties have been attributed to various classes of withanolide compounds. The
objective of the present study was to investigate the inter- and intraspecific
genetic variation present in 35 individuals of W. somnifera and 5 individuals of
W. coagulans using AFLP (amplified fragment length polymorphism) marker
technique. The information about genetic variation determined from AFLP data for
40 individuals was employed to estimate similarity matrix value based on
Jaccard's coefficient. The similarity values were further used to construct a
phenetic dendrogram revealing the genetic relationships. The dendrogram
generated by UPGMA (unweighted pair group method of arithmetic averages)
distinguished W. somnifera from W. coagulans and formed two major clusters.
These two main clusters shared a similarity coefficient of 0.3, correlating with
the high level of polymorphism detected. The dendrogram further separated W.
somnifera into three subclasses corresponding to Kashmiri and Nagori groups and
an intermediate type. The AFLP profile of Kashmiri individuals was distinct from
that of the Nagori group of plants. The intermediate genotype was distinct as it
shared bands with both the Kashmiri and Nagori individuals, even though it was
identified as a Kashmiri morphotype. Furthermore, the intermediate type shared a
similarity coefficient of 0.8 with the Kashmiri individuals. The present work
revealed low levels of variation within a population though high levels of
polymorphism were detected between Nagori and Kashmiri populations. The ability
of AFLP markers for efficient and rapid detection of genetic variations at the
species as well as intraspecific level qualifies it as an efficient tool for
estimating genetic similarity in plant species and effective management of
genetic resources.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11195351 [PubMed - indexed for MEDLINE]

127: Phytomedicine. 2000 Dec;7(6):499-507.

Curative property of Withania somnifera Dunal root in the context of
carbendazim-induced histopathological changes in the liver and kidney of rat.

Akbarsha MA, Vijendrakumar S, Kadalmani B, Girija R, Faridha A.

Department of Animal Science, School of Life Sciences, Bharathidasan University,
Tiruchirappalli, India. [email protected]

The liver and kidney of rat underwent severe histopathological lesions when
treated with a single bolus dose of carbendazim, a fungicide, particularly
affecting the hepatocytes and the renal corpuscles, respectively. The effects
appear to be manifestations of the microtubule-disrupting activity of
carbendazim. Treatment of carbendazim-treated rats with the powder of tuberous
root of Withania somnifera (Ashwagandha) for 48 days resulted in complete cure
of these organs. The results indicate that Withania somnifera would be an
effective curative for carbendazim-induced histopathological changes in the
liver and kidney.

PMID: 11194179 [PubMed - indexed for MEDLINE]

128: Phytomedicine. 2000 Dec;7(6):463-9.

Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an
experimental study.

Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S.

Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu
University, Varanasi, India. [email protected]

The roots of Withania somnifera (WS) are used extensively in Ayurveda, the
classical Indian system of medicine, and WS is categorized as a rasayana, which
are used to promote physical and mental health, to provide defence against
disease and adverse environmental factors and to arrest the aging process. WS
has been used to stabilize mood in patients with behavioural disturbances. The
present study investigated the anxiolytic and antidepressant actions of the
bioactive glycowithanolides (WSG), isolated from WS roots, in rats. WSG (20 and
50 mg/kg) was administered orally once daily for 5 days and the results were
compared by those elicited by the benzodiazepine lorazepam (0.5 mg/kg, i.p.) for
anxiolytic studies, and by the tricyclic anti-depressant, imipramine (10 mg/kg,
i.p.), for the antidepressant investigations. Both these standard drugs were
administered once, 30 min prior to the tests. WSG induced an anxiolytic effect,
comparable to that produced by lorazepam, in the elevated plus-maze, social
interaction and feeding latency in an unfamiliar environment, tests. Further,
both WSG and lorazepam, reduced rat brain levels of tribulin, an endocoid marker
of clinical anxiety, when the levels were increased following administration of
the anxiogenic agent, pentylenetetrazole. WSG also exhibited an antidepressant
effect, comparable with that induced by imipramine, in the forced swim-induced
'behavioural despair' and 'learned helplessness' tests. The investigations
support the use of WS as a mood stabilizer in clinical conditions of anxiety and
depression in Ayurveda.

PMID: 11194174 [PubMed - indexed for MEDLINE]

129: J Ethnopharmacol. 2001 Feb;74(2):173-9.

Screening of Yemeni medicinal plants for antibacterial and cytotoxic activities.

Ali NA, Julich WD, Kusnick C, Lindequist U.

Pharmacognosy Department, Faculty of Medicine and Health Sciences, Sana'a
University, Sana'a, Yemen.

Ethanolic extracts of 20 selected plant species used by Yemeni traditional
healers to treat infectious diseases were screened for their antibacterial
activity against both Gram-positive and Gram-negative bacteria, as well as for
cytotoxic activity. Fourteen of the ethanolic extracts showed variable degrees
of antibacterial activity. The active ethanolic extracts were partitioned
between ethyl acetate and water for a first separation. The ethyl acetate
extract of Lawsonia inermis was found to be the most active one against all
bacteria in the test system. Other promising results could be obtained from
extracts of Aloe perryi, Indigofera oblongifolia, Meriandra benghalensis and
Ziziphus spina christi. Additionally, the ethanolic extracts of the 20 plants
under investigation were tested for their cytotoxic effects on FL-cells using
the neutral red assay. Extracts of Calotropis procera, Chenopodium murale,
Pulicaria orientalis, Tribulus terrestris and Withania somniferum displayed a
remarkable activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 11167035 [PubMed - indexed for MEDLINE]

130: J Ethnopharmacol. 2001 Jan;74(1):1-6.

Anti-oxidant effect of Withania somnifera glycowithanolides in chronic footshock
stress-induced perturbations of oxidative free radical scavenging enzymes and
lipid peroxidation in rat frontal cortex and striatum.

Bhattacharya A, Ghosal S, Bhattacharya SK.

Drug Research and Development Centre, Calcutta, India.

The antioxidant activity of Withania somnifera (WS) glycowithanolides was
assessed in chronic footshock stress induced changes in rat brain frontal cortex
and striatum. The stress procedure, given once daily for 21 days, induced an
increase in superoxide dismutase (SOD) and lipid peroxidation (LPO) activity,
with concomitant decrease in catalase (CAT) and glutathione peroxidase (GPX)
activities in both the brain regions. WS glycowithanolides (WSG), administered
orally 1 h prior to the stress procedure for 21 days, in the doses of 10, 20 and
50 mg/kg, induced a dose-related reversal of the stress effects. Thus, WSG
tended to normalise the augmented SOD and LPO activities and enhanced the
activities of CAT and GPX. The results indicate that, at least part of chronic
stress-induced pathology may be due to oxidative stress, which is mitigated by
WSG, lending support to the clinical use of the plant as an antistress
adaptogen.

PMID: 11137343 [PubMed - indexed for MEDLINE]

131: Indian J Exp Biol. 2000 Jun;38(6):607-9.

Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania
somnifera, Dunal) root.

Andallu B, Radhika B.

Department of Home Science, Sri Satya Sai Institute of Higher Learning,
Anantapur 515001, India.

Hypoglycemic, diuretic and hypocholesterolemic effects of roots of W. somnifera
(ashvagandha) were assessed on human subjects. Six mild NIDDM subjects and six
mild hypercholesterolemic subjects were treated with the powder of roots of W.
somnifera for 30 days. Suitable parameters were studied in the blood and urine
samples of the subjects along with dietary pattern before and at the end of
treatment period. Decrease in blood glucose was comparable to that of an oral
hypoglycemic drug. Significant increase in urine sodium, urine volume,
significant decrease in serum cholesterol, triglycerides, LDL (low density
lipoproteins) and VLDL (very low density lipoproteins) cholesterol were observed
indicating that root of W. somnifera is a potential source of hypoglycemic,
diuretic and hypocholesterolemic agents. Clinical observations revealed no
adverse effects.

Publication Types:
Clinical Trial
Controlled Clinical Trial

PMID: 11116534 [PubMed - indexed for MEDLINE]

132: Phytother Res. 2000 Nov;14(7):568-70.

Effect of Withania somnifera glycowithanolides on iron-induced hepatotoxicity in
rats.

Bhattacharya A, Ramanathan M, Ghosal S, Bhattacharya SK.

Drug Research and Development Centre, Calcutta, India.

Glycowithanolides, consisting of equimolar concentrations of sitoindosides VII-X
and withaferin A, isolated from the roots of Withania somnifera Dunal, have been
reported to have an antioxidant effect in the rat brain frontal cortex and
striatum. In the present study, the effect of 10 days of oral administration of
these active principles, in graded doses (10, 20 and 50 mg/kg), was noted on
iron overload (FeSo(4), 30 mg/kg, i.p.) induced hepatotoxicity in rats. Apart
from hepatic lipid peroxidation (LPO), the serum enzymes, alanine
aminotransferase, aspartate aminotransferase and lactate dehydrogenase, were
assessed as indices of hepatotoxicity. Silymarin (20 mg/kg, p.o.) was used for
comparison. Iron overload induced marked increase in hepatic LPO and serum
levels of the enzymes, which was attenuated by WSG in a dose-related manner, and
by silymarin. The results indicate that the reported use of WS in Ayurveda for
hepatoprotection against heavy metals and other environmental toxins, may be due
the antioxidant action of WSG. Copyright 2000 John Wiley & Sons, Ltd.

PMID: 11054855 [PubMed - indexed for MEDLINE]

133: J Exp Clin Cancer Res. 2000 Jun;19(2):165-7.

Effect of Withania somnifera on 20-methylcholanthrene induced fibrosarcoma.

Davis L, Kuttan G.

Amala Cancer Research Centre, Amala Nagar Thrissur, Kerala, India.

Administration of an extract from the root of the plant Withania somnifera
(20mg/dose/animal i.p) was found to inhibit the 20-methylcholanthrene induced
sarcoma development in mice and increase the life span of tumour bearing
animals. Administration of Withania could inhibit the lipid peroxide formation
(152 nanomoles/mg protein) (P<0.01) compared with control (198 nanomoles/mg
protein). Withania could increase the GSH level (7.7 micromoles/mg protein)
which was lowered in control tumour bearing animals (3.96 micromoles/mg
protein). GST level was also significantly increased (451 micromoles/min/mg
protein) (P<0.001) in Withania treated animals compared to control animals (205
micromoles/min/mg protein). All the animals in the control group developed
sarcoma by the 80th day of carcinogen administration. Only 3 animals in the
Withania treated group developed sarcoma by the 105th day. In control animals
the survival rate was 40% but in the Withania treated group the survival rate
was 100% after 15 weeks of carcinogen treatment. These results indicate that
Withania could inhibit 20-methylcholanthrene induced sarcoma development in
mice.

PMID: 10965813 [PubMed - indexed for MEDLINE]

134: Altern Med Rev. 2000 Aug;5(4):334-46.

Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a
review.

Mishra LC, Singh BB, Dagenais S.

Los Angeles College of Chiropractic (LACC), 16200 E Amber Valley Dr., Whittier,
CA 90609-1166. [email protected]

OBJECTIVE: The objective of this paper is to review the literature regarding
Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine.
Specifically, the literature was reviewed for articles pertaining to chemical
properties, therapeutic benefits, and toxicity. DESIGN: This review is in a
narrative format and consists of all publications relevant to ashwagandha that
were identified by the authors through a systematic search of major computerized
medical databases; no statistical pooling of results or evaluation of the
quality of the studies was performed due to the widely different methods
employed by each study. RESULTS: Studies indicate ashwagandha possesses
anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory,
hemopoietic, and rejuvenating properties. It also appears to exert a positive
influence on the endocrine, cardiopulmonary, and central nervous systems. The
mechanisms of action for these properties are not fully understood. Toxicity
studies reveal that ashwagandha appears to be a safe compound. CONCLUSION:
Preliminary studies have found various constituents of ashwagandha exhibit a
variety of therapeutic effects with little or no associated toxicity. These
results are very encouraging and indicate this herb should be studied more
extensively to confirm these results and reveal other potential therapeutic
effects. Clinical trials using ashwagandha for a variety of conditions should
also be conducted.

Publication Types:
Review

PMID: 10956379 [PubMed - indexed for MEDLINE]

135: J Neurol Sci. 2000 Jun 15;176(2):124-7.

Comment in:
J Neurol Sci. 2001 Feb 15;184(1):89-92.

Association of L-DOPA with recovery following Ayurveda medication in Parkinson's
disease.

Nagashayana N, Sankarankutty P, Nampoothiri MR, Mohan PK, Mohanakumar KP.

Department of Kayachikitsa, Govt. Ayurveda College, - 695 001,
Thiruvananthapuram, India.

Ayurveda, the Indian system of traditional medicine, uses a concoction of
several spices, herbs and minerals for the treatment of diseases. In a clinical
prospective study we have evaluated the efficacy of Ayurveda treatment (a
concoction in cow's milk of powdered Mucuna pruriens and Hyoscyamus reticulatus
seeds and Withania somnifera and Sida cordifolia roots) in 18 clinically
diagnosed (with a mean Hoen and Yahr value of 2.22) parkinsonian patients. As
per Ayurveda principles, 13 patients underwent both cleansing (for 28 days) and
palliative therapy (56 days), 5 patients underwent palliative therapy alone (84
days). Only the former group showed significant improvement in activities of
daily living (ADL) and on motor examination as per UPDRS rating.
Symptomatically, they exhibited better response in tremor, bradykinesia,
stiffness and cramps as compared to the latter group. Excessive salivation
worsened in both the groups. Analyses of powdered samples in milk, as
administered in patients, revealed about 200 mg of L-DOPA per dose. The study
establishes the necessity of cleansing therapy in Ayurveda medication prior to
palliative therapy. It also reveals contribution of L-DOPA in the recovery as
observed in Parkinson' disease following Ayurveda medication.

PMID: 10930594 [PubMed - indexed for MEDLINE]

136: J Ethnopharmacol. 2000 Jul;71(1-2):193-200.

Immunomodulatory activity of Withania somnifera.

Davis L, Kuttan G.

Amala Cancer Research Centre, Amala Nagar P.O., 630 553, Kerala, Thrissur,
India.

Administration of an extract from the powdered root of the plant Withania
somnifera was found to stimulate immunological activity in Babl/c mice.
Treatment with five doses of Withania root extract (20 mg/dose/animal; i.p.) was
found to enhance the total WBC count (17125 cells/mm(3)) on 10th day. Bone
marrow cellularity (27x10(6) cells/femur) as well as alpha-esterase positive
cell number (1800/4000 cells) also increased significantly (P<0.001) after the
administration of Withania extract. Treatment with Withania extract along with
the antigen (SRBC) produced an enhancement in the circulating antibody titre and
the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC
(985 PFC/10(6) spleen cells) was obtained on the fourth day. Withania extract
inhibited delayed type hypersentivity reaction in mice (Mantoux test).
Administration of Withania extract also showed an enhancement in phagocytic
activity of peritoneal macrophages (76.5 pigmented cells/200) when compared to
control (31.5/200 cells) in mice. These results confirm the immunomodulatory
activity of W. somnifera extract, which is a known immunomodulator in indigenous
medicine.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10904163 [PubMed - indexed for MEDLINE]

137: J Ethnopharmacol. 2000 Jul;71(1-2):23-43.

Review on some plants of Indian traditional medicine with antioxidant activity.

Scartezzini P, Speroni E.

Department of Pharmacology, University of Bologna, Via Irnerio, 48, 40126,
Bologna, Italy.

A lot of medicinal plants, traditionally used for thousands of years, are
present in a group of herbal preparations of the Indian traditional health care
system (Ayurveda) named Rasayana proposed for their interesting antioxidant
activities. Among the medicinal plants used in ayurvedic Rasayana for their
therapeutic action, some of these have been throughly investigated. In the
present paper seven plants (Emblica officinalis L., Curcuma longa L., Mangifera
indica L., Momordica charantia L., Santalum album L., Swertia chirata Buch-Ham,
Withania somnifera (L.) Dunal) are viewed for their historical, etymological,
morphological, phytochemical and pharmacological aspects. The plants described
contain antioxidant principles, that can explain and justify their use in
traditional medicine in the past as well as the present. In order to identify
the plants with antioxidant activity in Ayurveda, a formulation of some
rasayanas with well defined antioxidant properties has been examinated. For this
purpose, we have considered Sharma's work on the preparation MAK4, MAK5, MA631,
MA 471, MA Raja's Cup, MA Student Rasayana, MA Ladies Rasayana.

Publication Types:
Review

PMID: 10904144 [PubMed - indexed for MEDLINE]

138: Neuroreport. 2000 Jun 26;11(9):1981-5.

Dendrite extension by methanol extract of Ashwagandha (roots of Withania
somnifera) in SK-N-SH cells.

Tohda C, Kuboyama T, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, Japan.

Extension of dendrites and axons in neurons may compensate for and repair
damaged neuronal circuits in the dementia brain. Our aim in the present study
was to explore drugs activating neurite outgrowth and regenerating the neuronal
network. We found that the methanol extract of Ashwagandha (roots of Withania
somnifera; 5 microg/ml) significantly increased the percentage of cells with
neurites in human neuroblastoma SK-N-SH cells. The effect of the extract was
dose- and time-dependent mRNA levels of the dendritic markers MAP2 and PSD-95 by
RT-PCR were found to be markedly increased by treatment with the extract,
whereas those of the axonal marker Tau were not. Immunocytochemistry
demonstrated the specific expression of MAP2 in neurites extended by the
extract. These results suggest that the methanol extract of Ashwagandha promotes
the formation of dendrites.

PMID: 10884056 [PubMed - indexed for MEDLINE]

139: Phytother Res. 2000 Jun;14(4):288-90.

The effect of extracts of Cynomorium coccineum and Withania somnifera on
gonadotrophins and ovarian follicles of immature Wistar rats.

Al-Qarawi AA, Abdel-Rahman HA, El-Badry AA, Harraz F, Razig NA, Abdel-Magied EM.

Department of Veterinary Medicine, King Saud University, P.O. Box 1482,
Buraidah, Kingdom of Saudi Arabia.

The effects of water extracts of Cynomorium coccineum and Withania somnifera on
ovarian follicular development and serum levels of FSH and LH were studied in
immature 17-day-old and 25-day-old-Wistar rats. Water extracts of the plants
were given to the animals per os in a dose of 47 mg/100 g body weight for 6
days. Serum levels of FSH and LH were measured by ELISA. Folliculogenesis was
studied with a light microscope. In 25-day-old rats, extracts of both plants
elicited significant changes in gonadotrophin levels coupled with a significant
increase in ovarian weight and profound folliculogenesis. Numerous primary,
secondary, tertiary and antral follicles were present. A distinct zona pellucida
was not seen and the oocyte was often detached. In 17-day-old animals there was
a significant increase-in body weight but without significant changes in the
ovarian weight and folliculogenesis. Copyright 2000 John Wiley & Sons, Ltd.

PMID: 10861976 [PubMed - indexed for MEDLINE]

140: Pharmacol Res. 2000 Jun;41(6):663-6.

Withania somnifera root extract in the regulation of lead-induced oxidative
damage in male mouse.

Chaurasia SS, Panda S, Kar A.

Thyroid Research Unit, School of Life Sciences, D.A. University, Khandwa Road,
Indore, 452 017, India.

The importance of Withania somnifera root extract in the regulation of lead
toxicity with special reference to lipid peroxidative process has been
investigated in liver and kidney tissues. While lead treatment (0.5 mg
kg(-1)body wt. day(-1)for 20 days) enhanced hepatic and renal lipid peroxidation
(LPO), administration of plant extract in the doses of 0.7 g kg(-1)and 1.4 g
kg(-1)body wt. day(-1)along with equivalent doses of lead acetate for 20 days
significantly decreased LPO and increased the activities of antioxidant enzymes,
viz., superoxide dismutase (SOD) and catalase (CAT), thus retaining normal
peroxidative status of the tissues. We suggest that the ameliorating role of
root extract of W. somnifera in the lead intoxicated mice could be the result of
its antiperoxidative action. Copyright 2000 Academic Press.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10816336 [PubMed - indexed for MEDLINE]

141: J Ethnopharmacol. 2000 Apr;70(1):57-63.

Adaptogenic and cardioprotective action of ashwagandha in rats and frogs.

Dhuley JN.

Pharmacology and Toxicology Section, Research Centre, Hindustan Antibiotics
Limited, Pimpri, Pune, India.

Pharmacological and metabolic effects of ashwagandha (Withania somnifera L.
(Solanaceae)) used in Ayurveda as a herbal tonic and health food were studied.
Ashwagandha was shown to increase swimming time in rats in physical working
capacity test, i.e. rats swimming endurance test. Significant increase in
relative heart weight and glycogen content in myocardium and liver was also
observed in ashwagandha treated group. Ashwagandha treatment increased the
duration of contractility in functional test for the resistance of frog heart
muscle towards the toxic action of strophanthin-K. Ashwaaandha treatment also
resulted in significant increase in coagulation time which attains normalcy 7
days after cessation of treatment. Ashwagandha possesses no toxicity up to a
dose of (100 mg/kg; p.o. for 180 days) and does not cause significant changes in
biochemical parameters in the blood serum of rats. Increase in catecholamine
content in the heart and aortic tissues and their decrease in adrenal glands are
unfavourable effects of high doses of ashwagandha. On the basis of these
observations, it was concluded that ashwagandha possesses adaptogenic,
cardiotropic, cardioprotective and anticoagulant properties.

PMID: 10720789 [PubMed - indexed for MEDLINE]

142: Phytother Res. 2000 Mar;14(2):122-5.

Adrenocorticosterone alterations in male, albino mice treated with Trichopus
zeylanicus, Withania somnifera and Panax ginseng preparations.

Singh A, Saxena E, Bhutani KK.

Department of Natural Products, National Institute of Pharmaceutical Education
and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), Near Chandigarh -
160062, India.

The levels of corticosterone were estimated by the HPLC method in the adrenal
glands of stressed (5 h constant swimming) male albino mice treated with
Trichopus zeylanicus, Withania somnifera and Panax ginseng preparations and
compared with non-treated stressed and normal controls. The treatments increased
the corticosterone levels in all the groups. The physical endurance (increased
survival time) of swimming mice also increased in all the treated groups, except
in the group treated with Withania somnifera powder (500 mg/kg, p.o.). Copyright
2000 John Wiley & Sons, Ltd.

PMID: 10685111 [PubMed - indexed for MEDLINE]

143: Cancer Lett. 2000 Jan 1;148(1):9-17.

Effect of Withania somnifera on cyclophosphamide-induced urotoxicity.

Davis L, Kuttan G.

Amala Cancer Research Centre, Amala Nagar, Kerala, India.

Administration of an extract from the plant Withania somnifera (Family:
Solanaceae) (20 mg/dose/animal; i.p.) for five days along with cyclophosphamide
(CTX) (1.5 mmol/kg body wt. i.p.) reduced the CTX induced urotoxicity.
Morphological analysis of the bladders of the CTX-treated group showed severe
inflammation and dark coloration whereas CTX along with the Withania-treated
group showed normal bladder morphology. The extract was found to reduce the
protein level in the serum (7.92 g/l) after 4 h of CTX treatment, which was
higher in the CTX alone-administered group (11.44 g/l). Blood urea N2 level
which was drastically enhanced (136.78 mg/100 ml) 2 after the CTX treatment was
significantly reduced (52.08 mg/100 ml) when the animals were treated with
Withania extract. Similarly the glutathione (GSH) content in both bladder (1.55
micromol/mg protein) and liver (3.76 micromol/mg protein) was enhanced
significantly (P<0.001) in the Withania-treated group compared with the CTX
alone-treated animals (bladder 0.5 micromol/mg protein; liver 1.2 micromol/mg
protein) Histopathological analysis of the bladder of CTX alone-treated group
showed severe necrotic damage where as the Withania somnifera-treated group
showed normal bladder architecture.

PMID: 10680587 [PubMed - indexed for MEDLINE]

144: J Ethnopharmacol. 1999 Nov 1;67(2):233-9.

Withania somnifera and Bauhinia purpurea in the regulation of circulating
thyroid hormone concentrations in female mice.

Panda S, Kar A.

School of Life Sciences, Devi Ahilya University, Vigyan Bhavan, Indore, India.
[email protected]

The effects of daily administration of Withania somnifera root extract (1.4 g/kg
body wt.) and Bauhinia purpurea bark extract (2.5 mg/kg body wt.) for 20 days on
thyroid function in female mice were investigated. While serum triiodothyronine
(T3) and thyroxine (T4) concentrations were increased significantly by Bauhinia,
Withania could enhance only serum T4 concentration. Both the plant extracts
showed an increase in hepatic glucose-6-phosphatase (G-6-Pase) activity and
antiperoxidative effects as indicated either by a decrease in hepatic lipid
peroxidation (LPO) and/or by an increase in the activity of antioxidant
enzyme(s). It appears that these plant extracts are capable of stimulating
thyroid function in female mice.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10619390 [PubMed - indexed for MEDLINE]

145: J Ethnopharmacol. 1999 Oct;67(1):27-35.

Studies on immunomodulatory activity of Withania somnifera (Ashwagandha)
extracts in experimental immune inflammation.

Agarwal R, Diwanay S, Patki P, Patwardhan B.

Bharati Vidyapeeth's Poona College of Pharmacy, Erandwane, Pune, India.

The immunomodulatory activities of an Indian Ayurvedic medicinal preparation,
i.e. extracts from Ashwagandha, Withania somnifera (L.) Dunal (Solanaceae),
namely WST and WS2, were studied in mice for immune inflammation: active paw
anaphylaxis and delayed type hypersensitivity (DTH). Immunomodulatory effect was
assessed in If IgE-mediated anaphylaxis as reduction of ovalbumin-induced paw
edema, in animals treated with WS2 at doses of 150 and 300 mg/kg, and the
results were compared with the standard drug disodium chromoglycate. In the DTH
model, the modulatory effect was assessed as potentiation or suppression of the
reaction, revealing an increase or decrease in mean foot pad thickness,
respectively. Potentiation of the DTH reaction was observed in animals treated
with cyclophosphamide at a dose of 20 mg/kg, WST at a dose of 1000 mg/kg and WS2
at a dose of 300 mg/kg. On the other hand, cyclophosphamide-induced potentiation
of DTH reaction was suppressed in animals treated with WST and WS2. A
significant increase in white blood cell counts and platelet counts was observed
in animals treated with WST. A protective effect in cyclophosphamide-induced
myelosuppression was observed in animals treated with WST and WS2, revealing a
significant increase in white blood cell counts and platelet counts.
Cyclophosphamide-induced immunosuppression was counteracted by treatment with
WS2, revealing significant increase in hemagglutinating antibody responses and
hemolytic antibody responses towards sheep red blood cells.

PMID: 10616957 [PubMed - indexed for MEDLINE]

146: Immunopharmacol Immunotoxicol. 1999 Nov;21(4):695-703.

Effect of Withania somnifera on cytokine production in normal and
cyclophosphamide treated mice.

Davis L, Kuttan G.

Amala Cancer Research Centre, Kerala, India.

Administration of an extract from the powdered root of the plant Withania
somnifera (Family: Solanaceae) enhanced the levels of Interferon gamma
(IFN-gamma) (75.87 pg/ml), Interleukin-2 (IL-2) (14.16 pg/ml) and Granulocyte
macrophage colony stimulating factor (GM-CSF) (49.22 pg/ml) in normal Balb/c
mice. The lowered levels of IFN gamma--(30 pg/ml), IL-2 (4.5 pg/ml) and GM-CSF
(19.12 pg/ml) after treatment with cyclophosphamide (CTX) was reversed by the
administration of Withania somnifera extract (IFN gamma--74 pg/ml; IL-2 7.5
pg/ml; GM-CSF 35.47 pg/ml). Withania extract lowered the levels of Tumour
necrosis factor alpha (TNF alpha) production. Administration of bonemarrow cells
from donor mice treated with Withania extract increased the spleen nodular
colonies in irradiated mice (8.33) compared to those treated with normal
bonemarrow cells (3.03). The number of nodular colonies increased significantly
when these animals were continued with Withania extract treatment. These results
indicate the immunopotentiating and myeloprotective effect of Withania somnifera
as seen from the enhancement of cytokine production and stem cell proliferation
and its differentiation.

PMID: 10584205 [PubMed - indexed for MEDLINE]

147: Phytother Res. 1999 Jun;13(4):275-91.

Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.

Rege NN, Thatte UM, Dahanukar SA.

Ayurveda Research Centre, Department of Pharmacology and Therapeutics, Seth GS
Medical College, Parel, Mumbai, India. [email protected]

Plants from all over the world such as Eleutherococcus senticosus, Panax
ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum
sanctum have been extensively evaluated for their adaptogenic potential.
However, none of them has been successfully introduced as an adaptogen in the
clinic. This paper discusses some of the problems in evaluation of adaptogens
which have precluded their inclusion as clinically useful drugs. We further
discuss our results with six rasayana plants from Ayurveda, which were studied
for their adaptogenic potential. The whole, aqueous, standardized extracts of
selected plants (Tinospora cordifolia, Asparagus racemosus, Emblica officinalis,
Withania somnifera, Piper longum and Terminalia chebula) were administered
orally to experimental animals, in a dose extrapolated from the human dose,
following which they were exposed to a variety of biological, physical and
chemical stressors. These plants were found to offer protection against these
stressors, as judged by using markers of stress responses and objective
parameters for stress manifestations. Using a model of cisplatin induced
alterations in gastrointestinal motility, the ability of these plants to exert a
normalizing effect, irrespective of direction of pathological change was tested.
All the plants reversed the effects of cisplatin on gastric emptying, while
Tinospora cordifolia and Asparagus racemosus also normalized cisplatin induced
intestinal hypermotility. Tinospora cordifolia was also tested for its ability
to modulate the changes occurring in the phagocytic activity of peritoneal
macrophages after exposure of rats to either carbon tetrachloride or horse
serum. It was found to normalize the phagocytic function irrespective to the
direction of change, complying to the definition of an adaptogen. All the plant
drugs were found to be safe in both acute and subacute toxicity studies. Studies
on the mechanisms of action of the plants revealed that they all produced
immunostimulation. The protection offered by Tinospora cordifolia against stress
induced gastric mucosal damage was lost if macrophage activity was blocked.
Emblica officinalis strengthened the defence mechanisms against free radical
damage induced during stress. The effect of Emblica officinalis appeared to
depend on the ability of target tissues to synthesize prostaglandins. Recent
data obtained with Tinospora cordifolia suggest that it may induce genotypic
adaptation, further opening the arena for more research and experimentation.

Publication Types:
Review

PMID: 10404532 [PubMed - indexed for MEDLINE]

148: Indian J Physiol Pharmacol. 1997 Oct;41(4):424-6.

Evidence for free radical scavenging activity of Ashwagandha root powder in
mice.

Panda S, Kar A.

School of Life Sciences, D.A. University, Vigyan Bhawan, Indore.

The effects of Ashwagandha root powder (0.7 and 1.4 g/kg body weight/day),
administered for 15 and 30 days, was investigated on lipid peroxidation (LPO),
superoxide dismutase (SOD) and catalase (CAT) activities in mice. While 15 days
treatment with Ashwagandha root powder did not produce any significant change,
30 days treatment produced a significant decrease in LPO, and an increase in
both SOD and CAT. Our findings indicate that Ashwagandha root powder possesses
free radical scavenging activity, which may be responsible for its
pharmacological effects.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 10235668 [PubMed - indexed for MEDLINE]

149: Indian J Physiol Pharmacol. 1998 Apr;42(2):299-302.

Subacute toxicity study of the combination of ginseng (Panax ginseng) and
ashwagandha (Withania somnifera) in rats: a safety assessment.

Aphale AA, Chhibba AD, Kumbhakarna NR, Mateenuddin M, Dahat SH.

Department of Pharmacology, Government Medical College, Aurangabad.

Ginseng (Panax ginseng) and Ashwagandha (Withania somnifera) are widely used as
geriatric tonics. Both individually have not shown any toxicity on long term
administration. Study was planned to assess the safety of the combination by
doing subacute toxicity study in rats with 90 days oral administration using
three doses. Food consumption, body weight, haematological, biochemical and
histopathological parameters were studied. There was significant increase in
body weight, food consumption and liver weight, and improved hematopoiesis was
observed. Brain, heart, lung, liver, spleen, kidneys, stomach, testis and
ovaries were normal on gross examination and histopathologically. Subacute
toxicity studies in rats did not reveal any toxicity.

PMID: 10225062 [PubMed - indexed for MEDLINE]

150: J Ethnopharmacol. 1999 Jan;64(1):91-3.

Antistressor effect of Withania somnifera.

Archana R, Namasivayam A.

Department of Physiology, Dr ALM PG. Institute of Basic Medical Sciences,
University of Madras, Taramani, India.

Withania somnifera is an Indian medicinal plant used widely in the treatment of
many clinical conditions in India. Its antistressor properties have been
investigated in this study using adult Wistar strain albino rats and cold water
swimming stress test. The results indicate that the drug treated animals show
better stress tolerance.

PMID: 10075127 [PubMed - indexed for MEDLINE]

151: J Ethnopharmacol. 1998 Oct;62(3):209-14.

Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera
extract in mice.

Davis L, Kuttan G.

Professor Amala Cancer Research Centre, Amala Nagar P.O., Kerala, India.

Administration of Withania somnifera extract (Solanaceae) was found to
significantly reduce leucopenia induced by cyclophosphamide (CTX) treatment. The
total WBC count on the 12th day of the CTX-treated group was 3720 cells/mm3 and
that of CTX along with Withania was 6120 cells/mm3. Treatment of Withania along
with CTX was found to significantly (P < 0.001) increase the bone marrow
cellularity (13.1 x 10(6) cells/femur) compared to CTX alone treated group (8 x
10(6) cells/femur). Administration of Withania extract increased the number of
alpha-esterase positive cells (1130/4000 cells) in the bone marrow of CTX
treated animals, compared to the CTX-alone treated group (687/4000 cells). The
major activity of Withania somnifera may be the stimulation of stem cell
proliferation. These studies indicate that Withania somnifera could reduce the
cyclophosphamide induced toxicity and its usefulness in cancer therapy.

PMID: 9849630 [PubMed - indexed for MEDLINE]

152: J Pharm Pharmacol. 1998 Sep;50(9):1065-8.

Changes in thyroid hormone concentrations after administration of ashwagandha
root extract to adult male mice.

Panda S, Kar A.

School of Life Sciences, D.A. University, Indore, India.

The importance of ashwagandha root extract in the regulation of thyroid function
with special reference to type-I iodothyronine 5'-monodeiodinase activity in
mice liver has been investigated. Although the root extract (1.4 g kg(-1))
administered daily for 20 days by gastric intubation increased serum
3,3',5-triiodothyronine (T3) and tetraiodothyronine (T4) concentrations and
hepatic glucose-6-phosphatase activity, hepatic iodothyronine 5'-monodeiodinase
activity did not change significantly. Furthermore, ashwagandha root extract
significantly reduced hepatic lipid peroxidation, whereas the activity of
antioxidant enzymes such as superoxide dismutase and catalase were increased.
These findings reveal that the ashwagandha root extract stimulates thyroidal
activity and also enhances the antiperoxidation of hepatic tissue.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 9811169 [PubMed - indexed for MEDLINE]

153: J Nat Prod. 1998 Jun 26;61(6):812-4.

Two new ergostane-type steroidal lactones from Withania coagulans.

Atta-ur-Rahman A, Choudhary MI, Qureshi S, Gul W, Yousaf M.

International Center for Chemical Sciences, H.E.J. Research Institute of
Chemistry, University of Karachi, Karachi-75270, Pakistan.

Two new withanolides (steroidal lactones) named coagulin F
[27-hydroxy-14,20-epoxy-1-oxo-(22R)-witha-3,5,24-trienolide] (1) and coagulin G
[17beta,27-dihydroxy-14,20-epoxy-1-oxo-(22R)-witha-2,5, 24-trienolide] (2) were
isolated from the whole plant of Withania coagulans, and their structures were
deduced by spectral analysis.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9644072 [PubMed - indexed for MEDLINE]

154: J Ethnopharmacol. 1998 Mar;60(2):173-8.

Effect of ashwagandha on lipid peroxidation in stress-induced animals.

Dhuley JN.

Hindustan Antibiotics Limited, Department of Pharmacology and Toxicology,
Research Centre, Pimpri, Pune, India.

The aqueous suspension of root extract of an Indian drug ashwagandha (Withania
somnifera L. (Solanaceae)) was evaluated for its effect on lipid peroxidation
(LPO) in stress-induced animals. Elevation of LPO was observed in rabbits and
mice after intravenous administration of 0.2 microg/kg of lipopolysaccharide
(LPS: from Klebsiella pneumoniae) and 100 microg/kg of peptidoglycan (PGN: from
Staphylococcus aureus), respectively. The peak was reached immediately after PGN
and 2-6 h after LPS administration. Simultaneous oral administration of
ashwagandha (100 mg/kg) prevented the rise in LPO in rabbits and mice.

PMID: 9582008 [PubMed - indexed for MEDLINE]

155: Immunopharmacol Immunotoxicol. 1998 Feb;20(1):191-8.

Therapeutic efficacy of Ashwagandha against experimental aspergillosis in mice.

Dhuley JN.

Pharmacology and Toxicology Division, Hindustan Antibiotics Limited, Pimpri,
Pune, India.

Therapeutic efficacy of an Indian Ayurvedic medicinal preparation, Ashwagandha
[Withania somnifera L. Dunal (Solanceae; root)] was evaluated against
experimental aspergillosis in Balb/c mice. Ashwagandha given orally once daily
for 7 consecutive days in a dose of 100 mg/kg after intravenous infection of
Aspergillus fumigatus prolonged the survival period of infected mice. This
protective activity was probably related to the observed increases in
phagocytosis and intracellular killing of peritoneal macrophages induced by
Ashwaganda treatment. The number of peripheral leukocytes was not modified,
excluding a possibility of mobilization of cells from other compartments. On the
basis of these findings, the probable mechanism underlying the protective action
of Ashwagandha against systemic Aspergillus infection was discussed in relation
with its possible activity to activate the macrophage function.

PMID: 9543708 [PubMed - indexed for MEDLINE]

156: J Ethnopharmacol. 1997 Sep;58(1):15-20.

Effect of some Indian herbs on macrophage functions in ochratoxin A treated
mice.

Dhuley JN.

Department of Pharmacology and Toxicology, Research Centre, Hindustan
Antibiotics Limited, Pimpri, India.

The effect of Indian herbs namely, Asparagus racemosus, Tinospora cordifolia,
Withania somnifera and Picrorhiza kurrooa on the functions of macrophages
obtained from mice treated with the carcinogen ochratoxin A (OTA) was
investigated. The chemotactic activity of murine macrophages was significantly
decreased by 17 weeks of treatment with OTA compared with controls. Production
of interleukin-1 (IL-1) and tumor necrosis factor (TNF) was also markedly
reduced. Treatment with Asparagus racemosus, Tinospora cordifolia, Withania
somnifera and Picrorhiza kurrooa significantly inhibited OTA-induced suppression
of chemotactic activity and production of IL-1 and TNF-alpha by macropahges.
Moreover, we found that Withania somnifera treated macrophage chemotaxis and
that Asparagus racemosus induced excess production of TNF-alpha when compared
with controls.

Publication Types:
Comparative Study

PMID: 9324000 [PubMed - indexed for MEDLINE]

157: J Ethnopharmacol. 1997 Aug;57(3):213-7.

Inhibition of morphine tolerance and dependence by Withania somnifera in mice.

Kulkarni SK, Ninan I.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Punjab
University, Chandigarh, India.

Chronic treatment with Withania somnifera (Ws) (family: Solanaceae, 100 mg/kg)
commercial root extract followed by saline on days 1-9 failed to produce any
significant change in tailflick latency from the saline pretreated group in
mice. However, repeated administration of Ws (100 mg/kg) for 9 days attenuated
the development of tolerance to the analgesic effect of morphine (10 mg/kg). Ws
(100 mg/kg) also suppressed morphine-withdrawal jumps, a sign of the development
of dependence to opiate as assessed by naloxone (2 mg/kg) precipitation
withdrawal on day 10 of testing.

Publication Types:
Comparative Study

PMID: 9292416 [PubMed - indexed for MEDLINE]

158: Br J Radiol. 1997 Jun;70(834):599-602.

Modification of bone marrow radiosensensitivity by medicinal plant extracts.

Ganasoundari A, Zare SM, Devi PU.

Department of Radiobiology, Kasturba Medical College, Manipal, India.

Withaferin A (WA), a steroidal lactone, and Plumbagin (Pl), a naphthoquinone,
from the roots of Withania somnifera and Plumbago rosea, respectively, have been
shown to possess growth inhibitory and radiosensitizing effects on experimental
mouse tumours. An aqueous extract of the leaves of Ocimum sanctum (OE) was found
to protect mice against radiation lethality. Therefore, the radiomodifying
effects of the above plant products on the bone marrow of the adult Swiss mouse
was studied. Single doses of WA (30 mg kg-1) or Pl (5 mg kg-1) were injected
intraperitoneally (ip) and OE (10 mg kg-1) was injected ip once daily for five
consecutive days. Administration of extracts was followed by 2 Gy whole body
gamma irradiation. Bone marrow stem cell survival was studied by an exogenous
spleen colony unit (CFU-S) assay. The effects of WA and Pl were compared with
that of cyclophosphamide (CP) and radioprotection by OE was compared with that
of WR-2721 (WR). Radiation reduced the CFU-S to less than 50% of normal. WA, CP
and Pl significantly enhanced this effect and reduced the CFU-S to almost the
same extent (to < 20% of normal), although individually WA and Pl were less
cytotoxic than CP. These results indicate that radiosensitization by WA and Pl
is not tumour specific. OE significantly increased CFU-S compared with
radiotherapy (RT) alone. OE+RT gave a higher stem cell survival (p < 0.05) than
that produced by WR+RT. While WR alone had a toxic effect, OE treatment showed
no such effect, suggesting that the latter may have an advantage over WR in
clinical application.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9227253 [PubMed - indexed for MEDLINE]

159: Indian J Exp Biol. 1997 Mar;35(3):297-9.

Effect of Trasina, an Ayurvedic herbal formulation, on pancreatic islet
superoxide dismutase activity in hyperglycaemic rats.

Bhattacharya SK, Satyan KS, Chakrabarti A.

Department of Pharmacology, Banaras Hindu University, Varanasi, India.

Diabetes mellitus was induced in male CF strain rats by streptozotocin (STZ) and
hyperglycaemia and superoxide dismutase (SOD) activity of pancreatic islet cells
was assessed on days 7, 14, 21 and 28. STZ induced significant hyperglycaemia
and a concomitant decrease in islet cell SOD activity. Transina (TR), an
Ayurvedic herbal formulation comprising of Withania somnifera, Tinospora
cordifolia, Eclipta alba, Ocimum sanctum, Picrorrhiza kurroa and shilajit, had
little per se effect on blood sugar concentrations and islet SOD activity in
euglycaemic rats, in the doses of 100 and 200 mg/kg, p.o. administered once
daily for 28 days. However, these doses of TR induced a dose- related decrease
in STZ hyperglycaemia and attenuation of STZ induced decrease in islet SOD
activity. The results indicate that the earlier reported anti-hyperglycaemic
effect of TR may be due to pancreatic islet free radical scavenging activity,
the hyperglycaemic activity of STZ being the consequence of decrease in islet
SOD activity leading to the accumulation of degenerative oxidative free radicals
in islet beta-cells.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9332177 [PubMed - indexed for MEDLINE]

160: Indian J Exp Biol. 1997 Mar;35(3):236-9.

Antioxidant activity of glycowithanolides from Withania somnifera.

Bhattacharya SK, Satyan KS, Ghosal S.

Department of Pharmacology, Banaras Hindu University, Varanasi, India.

Antioxidant activity of active principles of Withania somnifera, consisting of
equimolar concentrations of sitoindosides VII-X and withaferin A, was
investigated for their effects on rat brain frontal cortical and striatal
concentrations of superoxide dismutase (SOD), catalase (CAT) and glutathione
peroxidase (GPX). Results were compared with effects induced by deprenyl, an
agent with well documented antioxidant activity. Active glycowithanolides of W.
somnifera (WSG) (10 and 20 mg/kg, i.p.), administered once daily for 21 days,
induced a dose-related increase in SOD, CAT and GPX activity in frontal cortex
and striatum, which was statistically significant on days 14 and 21, except with
the lower dose of WSG on GPX activity, where the effect was evident only on day
21. The data were comparable to those induced by deprenyl (2 mg/kg/day, i.p.)
with respect to SOD, CAT and GPX activities, which were evident by day 14. These
findings are consistent with the therapeutic use of W. somnifera as an Ayurvedic
rasayana and medhyarasayana. Antioxidant effect of active principles of W.
somnifera may explain, at least in part, the reported antistress,
immunomodulatory, cognition-facilitating, anti-inflammatory and anti-aging
effects produced by them in experimental animals, and in clinical situations.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 9332168 [PubMed - indexed for MEDLINE]

161: Neurochem Int. 1997 Feb;30(2):181-90.

Systemic administration of defined extracts from Withania somnifera (Indian
Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic
and GABAergic markers in rat brain.

Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V.

Paul Flechsig Institute for Brain Research, Department of Neurochemistry,
University of Leipzig, Germany.

Although some promising results have been achieved by acetylcholinesterase
inhibitors, an effective therapeutic intervention in Alzheimer's disease still
remains an important goal. Sitoindosides VII-X, and withaferin-A, isolated from
aqueous methanol extract from the roots of cultivated varieties of Withania
somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to
blackish brown exudation from steep rocks of the Himalaya mountain, are used in
Indian medicine to attenuate cerebral functional deficits, including amnesia, in
geriatric patients. The present investigation was conducted to assess whether
the memory-enhancing effects of plant extracts from Withania somnifera and
Shilajit are owing to neurochemical alterations of specific transmitter systems.
Therefore, histochemistry to analyse acetylcholinesterase activity as well as
receptor autoradiography to detect cholinergic, glutamatergic and GABAergic
receptor subtypes were performed in brain slices from adult male Wistar rats,
injected intraperitoneally daily with an equimolar mixture of sitoindosides
VII-X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at
doses of 40 mg/kg of body weight for 7 days. Administration of Shilajit led to
reduced acetylcholinesterase staining, restricted to the basal forebrain nuclei
including medial septum and the vertical limb of the diagonal band. Systemic
application of the defined extract from Withania somnifera, however, led to
differential effects on AChE activity in basal forebrain nuclei: slightly
enhanced AChE activity was found in the lateral septum and globus pallidus,
whereas in the vertical diagonal band AChE activity was reduced following
treatment with sitoindosides VII-X and withaferin-A. These changes were
accompanied by enhanced M1-muscarinic cholinergic receptor binding in lateral
and medial septum as well as in frontal cortices, whereas the M2-muscarinic
receptor binding sites were increased in a number of cortical regions including
cingulate, frontal, piriform, parietal and retrosplenial cortex. Treatment with
Shilajit or the defined extract from Withania somnifera affected neither GABAA
and benzodiazepine receptor binding nor NMDA and AMPA glutamate receptor
subtypes in any of the cortical or subcortical regions studied. The data suggest
that Shilajit and the defined extract from Withania somnifera affect
preferentially events in the cortical and basal forebrain cholinergic signal
transduction cascade. The drug-induced increase in cortical muscarinic
acetylcholine receptor capacity might partly explain the cognition-enhancing and
memory-improving effects of extracts from Withania somnifera observed in animals
and humans.

Publication Types:
Comparative Study
In Vitro
Research Support, Non-U.S. Gov't

PMID: 9017665 [PubMed - indexed for MEDLINE]

162: Planta Med. 1996 Dec;62(6):571-3.

Withanolide Production by Root Cultures of Withania somnifera Transformed with
Agrobacterium rhizogenes.

Ray S, Ghosh B, Sen S, Jha S.

Centre of Advanced Study, Department of Botany, Calcutta University, 35, B. C.
Road, Calcutta 700019, India.

Transformed root cultures of WITHANIA SOMNIFERA Dunal (Solanaceae) were obtained
by infecting shoots cultured IN VITRO with AGROBACTERIUM RHIZOGENES LBA 9402.
They grew axenically in the absence of exogenous plant growth regulators in
Murashige and Skoog's medium containing 3% (w/v) sucrose. The root cultures
synthesized several withanolides of which withanolide D was isolated and
identified. Transformed root (clone HR (1)) showed a growth index of 20.07 and a
withanolide D yield of 0.30 mg g (-1) DW. The productivity of withanolide D in
transformed roots (0.181 mg 1 (-1) d (-1)) was higher than in untransformed root
cultures (0.026 mg 1 (-1) d (-1)).

PMID: 17252504 [PubMed - in process]

163: Indian J Exp Biol. 1996 Oct;34(10):927-32.

Withania somnifera Dunal (Ashwagandha): potential plant source of a promising
drug for cancer chemotherapy and radiosensitization.

Devi PU.

Department of Radiobiology, Kasturba Medical College, Manipal, India.

Study of antitumor and radiosensitizing properties of W. somnifera
(Ashwagandha), a well known medicinal plant, have yielded encouraging results.
The alcoholic extract of the dried roots of the plant as well as the active
component withaferin A isolated from the extract showed significant antitumor
and radiosensitizing effects in experimental tumors in vivo, without any
noticeable systemic toxicity. Withaferin A gave a sensitizer enhancement ratio
of 1.5 for in vitro cell killing of V79 Chinese hamster cells at a non toxic
concentration of approximately 2 microM. The mechanism of action of this
compound is not known. The studies so far indicate that W. somnifera could prove
to be a good natural source of a potent and relatively safe
radiosensitizer/chemotherapeutic agent. Further studies are needed to explore
the clinical potential of this plant for cancer therapy.

Publication Types:
Review

PMID: 9055640 [PubMed - indexed for MEDLINE]

164: Indian J Exp Biol. 1996 Sep;34(9):854-6.

Use of Withania somnifera Dunal as an adjuvant during radiation therapy.

Kuttan G.

Amala Cancer Research Centre, Amala Nagar, Thrissur, India.

Withania somnifera popularly known as Aswagandha is used in several indigenous
drug preparations. Administration of a 75% methanolic extract of the plant was
found to significantly increase the total WBC count in normal Balb/c mice and
reduce the leucopenia induced by sublethal dose of gamma radiation. Treatment
with W. somnifera was found to increase the bone marrow cellularity
significantly, the percentage increase being 146.3. Treatment with W. somnifera
had normalised the ratio of normochromatic erythrocytes and polychromatic
erythrocytes in mice after the radiation exposure. Major activity of W.
somnifera seemed to be in the stimulation of stem cell proliferation.

PMID: 9014519 [PubMed - indexed for MEDLINE]

165: Planta Med. 1996 Jun;62(3):287-8.

Withanolide Composition and in vitro Culture of Italian Withania somnifera.

Vitali G, Conte L, Nicoletti M.

Dipartimento di Genetica e Biologia Molecolare, Universita "La Sapienza", P. le
A. Moro 5, I-00185 Rome, Italy.

From Italian plants of WITHANIA SOMNIFERA six withanolides were isolated, whose
structures allowed us to assign the Italian race of W. SOMNIFERA to the Israel
chemotype III. IN VITRO cultures of Italian W. SOMNIFERA under different
conditions were obtained, as well as infection by AGROBACTERIUM RHIZOGENES. HPLC
analysis of IN VITRO derived tissues showed low contents of withanolides.

PMID: 17252448 [PubMed - in process]

166: J Ethnopharmacol. 1996 Feb;50(2):69-76.

Studies on the immunomodulatory effects of Ashwagandha.

Ziauddin M, Phansalkar N, Patki P, Diwanay S, Patwardhan B.

Medinova Diagnostics Center, Indian Drugs Research Association, Pune, India.

The immunomodulatory activity of an Indian Ayurvedic medicinal preparation,
Ashwagandna (Withania somnifera (L. Dunal)) was studied in mice with
myelosuppression induced by one or more of the following three compounds:
cyclophosphamide, azathioprin, or prednisolone. The assessment of
immunomodulatory activity was carried out by hematological and serological
tests. A significant modulation of immune reactivity was observed in all the
three animal models used. Ashwagandha prevented myelosuppression in mice treated
with all three immunosuppressive drugs tested. A significant increase in
hemoglobin concentration (P < 0.01), red blood cell count (P < 0.01), white
blood cell count (P < 0.05), platelet count (P < 0.01), and body weight (P <
0.05) was observed in Ashwagandha-treated mice as compared with untreated
(control) mice. We also report an immunostimulatory activity: treatment with
Ashwagandha was accompanied by significant increases in hemolytic antibody
responses towards human erythrocytes.

PMID: 8866726 [PubMed - indexed for MEDLINE]

167: Int J Radiat Biol. 1996 Feb;69(2):193-7.

Withaferin A: a new radiosensitizer from the Indian medicinal plant Withania
somnifera.

Devi PU, Akagi K, Ostapenko V, Tanaka Y, Sugahara T.

Department of Radiobiology, Kasturba Medical College, Manipal, India.

Withaferin A, a steroidal lactone isolated from the roots of the Indian
medicinal plant Withania somnifera, reduced survival of V79 cells in a
dose-dependent manner. LD50 for survival was 16 microM. One-hour treatment with
a non-toxic dose of 2.1 microM before irradiation significantly enhanced cell
killing, giving a sensitizer enhancement ratio (SER) of 1.5 for 37% survival and
1.4 for 10% survival. SER increased with drug dose, but at higher doses the
increased lethality appears to be due to two effects-- drug toxicity and
radiosensitization. The drug induced a G2/M block, with a maximum accumulation
of cells in G2-M phase at 4 h after treatment with 10.5 microM withaferin A in 1
h. The applicability of this drug as a radiosensitizer in cancer therapy needs
to be explored.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8609455 [PubMed - indexed for MEDLINE]

168: Acta Oncol. 1996;35(1):95-100.

Antitumor and radiosensitizing effects of withaferin A on mouse Ehrlich ascites
carcinoma in vivo.

Sharada AC, Solomon FE, Devi PU, Udupa N, Srinivasan KK.

Department of Radiobiology, Kasturba Medical College, Manipal, Karnataka, India.

The antitumor and radiosensitizing effects of withaferin A (WA), a steroidal
lactone from Withania somnifera, was studied on Ehrlich ascites carcinoma in
vivo. The acute LD50(14) for WA in Swiss mice was approximately 80 mg/kg.
Twenty-four hours after i.p. inoculation of 10(6) tumor cells, WA was injected
i.p. at different dose fractions (5 or 7.5 mg/kg x 8, 10 mg/kg x 5, 20 or 30
mg/kg x 2) with or without abdominal gamma irradiation (RT, 75. Gy) after the
first drug dose. Increase in life span and tumor-free survival were studied up
to 120 days. The drug inhibited tumor growth and increased survival, which was
dependent on the WA dose per fraction rather than the total dose. Combination of
RT with all the drug schedules increased tumor cure and tumor-free survival, the
best effect seen after 2 fractions of 30 mg/kg each. In another experiment WA
was given as 2 (40 mg/kg x 2), 3 (30 mg/kg x 3) or 4 (20 mg/kg x 4) fractions at
5, 7 or 10 days after tumor inoculation with or without RT after the first drug
dose. At 7 and 10 days after inoculation the drug was effective only at 40 mg/kg
x 2, but with RT 30 mg/kg x 3 produced an equal effect (20% survival) on 7 day
old tumors.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8619948 [PubMed - indexed for MEDLINE]

169: Phytochemistry. 1995 Nov;40(4):1243-6.

Antifungal steroidal lactones from Withania coagulance.

Choudhary MI, Dur-e-Shahwar, Parveen Z, Jabbar A, Ali I, Atta-ur-Rahman.

H.E.J. Research Institute of Chemistry, University of Karachi, Pakistan.

Two new withanolides, 14,15 beta-epoxywithanolide I [(20S,22R) 17 beta, 20
beta-dihydroxy-14 beta,15 beta-epoxy-1-oxo-witha-3,5,24-trienolide] and 17
beta-hydroxywithanolide K (20S,22R) 14 alpha,17 beta,20
beta-trihydroxy-1-oxo-witha-2,5,24-trienolide] have been isolated from the whole
plant of Withania coagulance and their structures were elucidated by
spectroscopic techniques. The latter compound was found to be active against a
number of potentially pathogenic fungi.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7492372 [PubMed - indexed for MEDLINE]

170: Cancer Lett. 1995 Aug 16;95(1-2):189-93.

In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse
Ehrlich ascites carcinoma.

Devi PU, Sharada AC, Solomon FE.

Department of Radiobiology, Kasturba Medical College, Karnataka, India.

Adult Swiss albino mice were inoculated intraperitoneally (i.p.) with 10 (6)
Ehrlich ascites carcinoma cells. Twenty-four hours later they were given an i.p.
injection of 10-60 mg/kg of withaferin A (WA), isolated from the roots of
Withania somnifera. The tumor growth and tumor free animal survival were studied
for up to 120 days. In another experiment 30 mg/kg WA was injected i.p. to mice
at 1, 3 or 5 days after tumor cell injection with or without acute abdominal
exposure to 7.5 Gy gamma radiation and the tumor growth and 120-day survival
were studied. WA inhibited tumor growth and increased tumor free survival in a
dose-dependent manner. The drug ED50 for 120-day survival was approximately 30
mg/kg body wt. Drug treatment before irradiation synergistically increased
120-day even in advanced tumors. A dose of 30 mg/kg seems to be optimum for
combination with radiation.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7656229 [PubMed - indexed for MEDLINE]

171: J Ethnopharmacol. 1994 Dec;44(3):131-5.

A comparative pharmacological investigation of Ashwagandha and Ginseng.

Grandhi A, Mujumdar AM, Patwardhan B.

Indian Drugs Research Association, Pune.

The aqueous suspensions of roots of an Indian drug Ashwagandha and the Korean
drug Ginseng were tested comparatively for 2 pharmacological activities, namely
the anti-stress activity by the 'mice swimming endurance test' and anabolic
activity by noting gain in body weights and levator ani muscle in rats. A
significant increase in mice swimming time was shown by Ginseng (P < 0.001) and
Ashwagandha (P < 0.01) as compared to the control group. Significant increase in
body weights in the Ashwagandha treated group (P < 0.05) was better than Ginseng
(P < 0.5). Gain in wet weights of the levator ani muscle were also significant
in Ginseng (P < 0.001) and Ashwagandha (P < 0.01) treated groups, however, the
weight gain of dried levator ani muscles showed comparable results for both
these drugs (P < 0.01).

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 7898119 [PubMed - indexed for MEDLINE]

172: Tumori. 1994 Aug 31;80(4):306-8.

Chemoprotective action of Rasayanas against cyclosphamide toxicity.

Praveenkumar V, Kuttan R, Kuttan G.

Amala Cancer Research Centre, Thrissur, Kerala, India.

AIMS AND BACKGROUND: Mylosuppression has been found to be one of the major
drawbacks in cancer chemotherapy. Presently the effect of Rasayanas, an
indigenous herbal drug preparation having immunomodulatory activity, in reducing
myelosuppression and subsequent leukopenia was studied. METHODS: Animals were
injected cyclophosphamide (50 mg/kg b.wt. daily for 14 days) with or without
Rasayanas (50 mg/animal) and total white blood cells, bone marrow cellularity
and survival of the animals were determined. RESULTS: Oral administration of
Brahma Rasayana (BR) and Ashwagandha/Rasayana (AR) was found to protect mice
from cyclophosphamide induced leukopenia. Total white blood cell counts in BR
and AR treated animals on day 12 were 3800 and 3000 cells (mm3 respectively,
which was significantly high compared to that of controls (700 cells/mm3). When
the treatment was stopped on day 14 the value increased to 27,000 and 26,000
cells/mm3. The bone marrow cellularity were also significantly high in BR and AR
treated animals (3.45 x 10(6) and 2.38 x 16 cells femur respectively) compared
to that of controls. (0.72 x 10(6) cells/femur). CONCLUSION: The results
indicate the usefulness of Rasayanas in chemotherapy induced myelosuppression
and leukopenia.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7974804 [PubMed - indexed for MEDLINE]

173: J Ethnopharmacol. 1994 Aug;44(1):11-8.

Solanaceae as medicinal plants in Israel.

Dafni A, Yaniv Z.

Institute of Evolution, Haifa University, Israel.

In a recent survey, 106 local healers in Israel were interviewed concerning the
use of Solanaceae as medicinal plants. The main findings reveal that: (a) only
four species (Lycium europeaum, Solanum nigrum, Hyoscyamus aureus, Hyoscyamus
albus) are extensively used today; (b) the use of some traditional plants has
been almost abandoned (Datura spp., Mandragora autumnalis, Withania somnifera);
(c) today all the plants are applied externally, they are rarely used as
narcotics; (d) most use of these plants is local, only in a few cases is a
uniform use found throughout the whole country, and in all ethnic groups; (e)
the extensive distribution of modern, safe narcotics, sedatives and anaesthetics
has reduced the use of the Solanaceae for these purposes.

Publication Types:
Review

PMID: 7990499 [PubMed - indexed for MEDLINE]

174: Indian J Exp Biol. 1993 Jul;31(7):607-11.

Antitumor and radiosensitizing effects of Withania somnifera (Ashwagandha) on a
transplantable mouse tumor, Sarcoma-180.

Devi PU, Sharada AC, Solomon FE.

Department of Radiobiology, Kasturba Medical College, Manipal.

Antitumor and radiosensitizing effects of alcoholic root extract of W. somnifera
and their modification by heat were studied in vivo on Sarcoma-180 grown on the
dorsum of adult BALB/c mouse. Ashwagandha (AT) was injected (ip) at a dose of
500 mg/kg body wt for 10 consecutive days into mouse bearing tumor of 50 +/- 5
mm3, with or without a local treatment of 10 Gy gamma radiation (RT) or
hyperthermia at 43 degrees C for 30 min (HT) or both on 5th day of AT. The
response was assessed on the basis of tumor regression, growth delay, animal
survival and changes in the tumor GSH content. Ashwagandha, RT and HT
individually produced 18, 38 and 45% complete response (CR) respectively, but RT
gave the best long term survival. Ashwagandha increased the effect of radiation
on tumor regression as well as growth delay, but AT + HT gave a better tumor
cure. However, both these combinations gave almost identical long term survival,
which was not much higher than that produced by RT alone. The combination of
Ashwagandha for 10 days with one local exposure to RT followed by HT
significantly increased the tumor cure, growth delay of partially responding
tumors and animal survival. This combination also significantly and
synergistically depleted the tumor GSH level, with no recovery even at 3 hr
after treatment. It is concluded that Ashwagandha, in addition to having a tumor
inhibitory effect, also acts as a radiosensitizer and heat enhances these
effects. The severe depletion in the tumor GSH content by the combination
treatment must have enhanced the tumor response, as the inherent protection by
the thiol will be highly reduced.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 8225418 [PubMed - indexed for MEDLINE]

175: J Ethnopharmacol. 1992 Sep;37(2):113-6.

Anti-granuloma activity of Iraqi Withania somnifera.

al-Hindawi MK, al-Khafaji SH, Abdul-Nabi MH.

Pharmacognosy and Pharmacology Department, Scientific Research Council, Baghdad,
Iraq.

The granuloma-tissue formation inhibiting activity of various fractions of an
extract of the aerial parts of Withania somnifera were established using
subcutaneous cotton-pellet implantation in rats. Antiinflammatory activity was
retained in the methanolic fractions of the plant extract and was comparable to
that of a 5 mg/kg dose of hydrocortisone sodium succinate. Activity was
attributed to the high content of biologically active steroids in the plant, of
which withaferin A is known to be a major component.

PMID: 1434685 [PubMed - indexed for MEDLINE]

176: Indian J Exp Biol. 1992 Mar;30(3):169-72.

In vivo growth inhibitory effect of Withania somnifera (Ashwagandha) on a
transplantable mouse tumor, Sarcoma 180.

Devi PU, Sharada AC, Solomon FE, Kamath MS.

Department of Radiobiology, Kasturba Medical College, Manipal, India.

Withania somnifera is a medicinal plant used in the treatment of a variety of
ailments in the Ayurvedic system. Alcoholic extract of the root of the plant was
injected(ip) at daily doses of 200 to 1000 mg/kg body wt for 15 days starting
from 24 hr after intradermal inoculation of 5 x 10(5) cells of S-180 in BALB/c
mice. Solid tumor growth was monitored for 100 days. Doses of 400 mg/kg and
above produced complete regression of tumor after an initial growth, the
percentage of complete response (CR) increasing with increasing drug dose. A 55%
CR was obtained at 1000 mg/kg drug administration, but this dose also produced
some mortality among the animals. A significant increase in the volume doubling
time and growth delay was seen when the drug dose was increased from 500 to 750
mg/kg body wt, but further increase in drug dose to 1000 mg/kg did not produce
any significant increase in these responses. Cumulative doses of 7.5 to 10 g at
daily doses of 500 or 750 mg/kg seems to produce a good response in this tumor.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 1512021 [PubMed - indexed for MEDLINE]

177: Indian J Med Res. 1991 Aug;94:312-5.

Pharmacological effects of Withania somnifera root extract on GABAA receptor
complex.

Mehta AK, Binkley P, Gandhi SS, Ticku MK.

Department of Pharmacology, University of Texas Health Science Center.

A methanolic extract of W. somnifera root inhibited the specific binding of
[3H]GABA and [35S]TBPS, and enhanced the binding of [3H]flunitrazepam to their
putative receptor sites. The extract (5 micrograms) inhibited [3H]GABA binding
by 20 +/- 6 per cent whereas a concentration of 1 mg of the extract produced 100
per cent inhibition. The extract (5-100 micrograms) produced 20 +/- 4 to 91 +/-
16 per cent enhancement of [3H]flunitrazepam binding. In functional studies
using 36Cl-influx assay in mammalian spinal cord neurons, W. somnifera root
extract increased 36Cl-influx in the absence of GABA. This effect on 36Cl-influx
was blocked by bicuculline and picrotoxin; and enhanced by diazepam. These
results suggest that the W. somnifera extract contains an ingredient which has a
GABA-mimetic activity.

Publication Types:
In Vitro

PMID: 1660034 [PubMed - indexed for MEDLINE]

178: Pak J Pharm Sci. 1991 Jul;4(2):113-23.

New bioactive compounds of plant origin.

Kazmi SU, Ali SN, Jamal SA, Atta-ur-Rahman.

Department of Microbiology, University of Karachi, Karachi-75270, Pakistan.

Crude extracts of Withania somnifera (WS) and Polygonum equisetiforme (PE) as
well as the pure compounds isolated therefrom were screened for antibacterial
and antifungal activity against 20 bacterial and 17 fungal cultures. The crude
extract of PE and WS inhibited the growth of T. mentagrophyte, M. canis and A.
boydii at an MIC of 450-500 microg/ml whereas the pure compounds inhibited the
growth at MIC of 300-350 micro/ml. Species of Corynebacterium, Bacillus,
Streptococcus and Staphylococcus were found to be highly susceptible to both the
crude sad the pure compounds. MIC values of both crude extracts for different
organisms tested were found to be higher (200-350 microg/ml) than the pure
compounds (150-170 microg/ml). The crude extract of PE did not inhibit the
growth of Ps. aeruginosa, however, the pure compound was found to be
bacteriostatic. Brine shrimp and BALB/c mice lethality test indicated that these
extracts maybe toxic at high concentration.

PMID: 16414690 [PubMed]

179: J Ethnopharmacol. 1991 May-Jun;33(1-2):91-5.

Treatment of osteoarthritis with a herbomineral formulation: a double-blind,
placebo-controlled, cross-over study.

Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B.

Bryamjee Jeejeebhoy Medical College, University of Poona, Pune, India.

The clinical efficacy of a herbomineral formulation containing roots of Withania
somnifera, the stem of Boswellia serrata, rhizomes of Curcuma longa and a zinc
complex (Articulin-F), was evaluated in a randomized, double-blind, placebo
controlled, cross-over study in patients with osteoarthritis. After a one-month
single blind run-in period, 42 patients with osteoarthritis were randomly
allocated to receive either a drug treatment or a matching placebo for a period
of three months. After a 15-day wash-out period the patients were transferred to
the other treatment for a further period of three months. Clinical efficacy was
evaluated every fortnight on the basis of severity of pain, morning stiffness,
Ritchie articular index, joint score, disability score and grip strength. Other
parameters like erythrocyte sedimentation rate and radiological examination were
carried out on a monthly basis. Treatment with the herbomineral formulation
produced a significant drop in severity of pain (P less than 0.001) and
disability score (P less than 0.05). Radiological assessment, however, did not
show any significant changes in both the groups. Side effects observed with this
formulation did not necessitate withdrawal of treatment.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 1943180 [PubMed - indexed for MEDLINE]

180: Rev Med Chir Soc Med Nat Iasi. 1990 Oct-Dec;94(3-4):603-5.

Contributions to the pharmacodynamic study of roots of Withania somnifera Dun
species of Pakistani origin. Note III: Testing of analgesic activity of
dichlormethanic and methanolic extract from Withania somnifera roots.

Sakka Mazen E, Pavelescu M, Grigorescu E.

Laboratory of Pharmacodynamics, Faculty of Pharmacy of Iasi, Romania.

Publication Types:
Comparative Study

PMID: 2131560 [PubMed - indexed for MEDLINE]

181: Rev Med Chir Soc Med Nat Iasi. 1990 Apr-Jun;94(2):385-7.

New data referring to chemistry of Withania somnifera species.

Elsakka M, Grigorescu E, Stanescu U, Stanescu U, Dorneanu V.

Faculty of Pharmacy, Department of Pharmacognosy, Institute of Medicine and
Pharmacy, Iasi.

The withanolides are a category of active principles of great pharmacodynamic
importance with regard to our own research. We obtained alkaloids, 18 fatty
acids, beta-sitesterol, polyphenols and phytosterols.

PMID: 2100857 [PubMed - indexed for MEDLINE]

182: J Ethnopharmacol. 1989 Sep;26(2):163-8.

Anti-inflammatory activity of some Iraqi plants using intact rats.

Al-Hindawi MK, Al-Deen IH, Nabi MH, Ismail MA.

Biological Research Centre, Scientific Research Council, Jadiriyah, Baghdad,
Iraqu.

Five plants (Myrtus communis, Apium graveolens, Matricaria chamomilla, Withania
somnifera and Achillea santolina) grown in Iraq were assessed for their
anti-inflammatory activity on intact rats by measuring the suppression of
carrageenan-induced paw edema produced by 1/10 of the intraperitoneal LD50 doses
for the respective 80% ethanol extracts. Acetylsalicylic acid was used as the
standard drug. Results showed that the plants possessed varying degrees of
anti-inflammatory activity and were classified in the following descending order
of activity: W. somnifera greater than A. graveolens greater than A. santolina
greater than M. chamomilla greater than M. communis.

PMID: 2601356 [PubMed - indexed for MEDLINE]

183: Rev Med Chir Soc Med Nat Iasi. 1989 Apr-Jun;93(2):349-50.

Withania somnifera, a plant with a great therapeutical future.

Elsakka M, Pavelescu M, Grigorescu E.

Withania somnifera Dun is a plant which drew the interest of many researchers in
several countries, either for its active principles or for the extremely
important pharmacodynamic or pharmacotherapeutic properties it has and first of
all for the content in withanolides, substances with a sterol structure.

PMID: 2814052 [PubMed - indexed for MEDLINE]

184: Indian J Exp Biol. 1988 Nov;26(11):877-82.

Long term effect of herbal drug Withania somnifera on adjuvant induced arthritis
in rats.

Begum VH, Sadique J.

PMID: 3248848 [PubMed - indexed for MEDLINE]

185: Biochem Med Metab Biol. 1987 Dec;38(3):272-7.

Effect of Withania somnifera on glycosaminoglycan synthesis in
carrageenin-induced air pouch granuloma.

Begum VH, Sadique J.

Department of Siddha Medicine, Faculty of Sciences, Tamil University, India.

The effect of W. somnifera on glycosaminoglycan synthesis in the granulation
tissue of carrageenin-induced air pouch granuloma was studied. W. somnifera was
shown to exert significant inhibitory effect on incorporation of 35S into the
granulation tissue. The uncoupling effect on oxidative phosphorylation (ADP/O
ratio reduction) was also observed in the mitochondria of granulation tissue.
Further, Mg2+ dependent ATPase activity was found to be influenced by W.
somnifera. W. somnifera also reduced the succinate dehydrogenase enzyme activity
in the mitochondria of granulation tissue.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 2963652 [PubMed - indexed for MEDLINE]

186: Plant Physiol. 1986 Oct;82(2):585-587.

Immunochemical Comparison of Glutamine Synthetases from Some Solanaceae Plants.

Botella JR, Canovas FM, Avila C, de Castro IN, Valpuesta V.

Departamento de Bioquimica, Facultad de Ciencias, Universidad de Malaga, 29071
Malaga, Spain.

The presence of different glutamine synthetase isoenzymes in different
Solanaceae plants and their relative antigenicities against antiglutamine
synthetase from tomato leaf serum were studied. All the plants tested showed one
glutamine synthetase isoenzyme except for Mandragora autumnalis, which showed
two, after discontinuous polyacrylamide gel electrophoresis and specific in situ
assay. Antigenicities were compared by the double immunodiffusion technique. The
Nicotiana glauca enzyme showed equal reactivity to that of Lycopersicon
esculentum, but its antigenicity was higher than Withania frutescens, Datura
stramonium, and Hyoscyamus niger. The study of relative antigenicities permitted
differentiation of the glutamine synthetase enzymes from uncultivated species of
Solanaceae.

PMID: 16665071 [PubMed - as supplied by publisher]

187: Planta Med. 1986 Feb;(1):61-3.

Pharmacological studies on leaves of Withania somnifera.

Sudhir S, Budhiraja RD, Miglani GP, Arora B, Gupta LC, Garg KN.

PMID: 3703993 [PubMed - indexed for MEDLINE]

188: J Ethnopharmacol. 1985 Jul;13(3):323-35.

Studies of medicinal plants of Sri Lanka. Part 14: Toxicity of some traditional
medicinal herbs.

Arseculeratne SN, Gunatilaka AA, Panabokke RG.

Seventy five medicinal plants of the traditional Ayurvedic pharmacopoeia of Sri
Lanka have been screened chemically for alkaloids and pyrrolizidine alkaloids.
Of these, Crotolaria juncea L. was found to contain pyrrolizidine alkaloids with
biological effects consistent with pyrrolizidine alkaloid toxicity. Feeding
trials in rats with three plants lacking pyrrolizidine alkaloids, namely Aegle
marmelos (L.) Corr., Hemidesmus indicus (L.) Ait. F. and Terminalia chebula
Retz. produced hepatic lesions which included central vein abnormalities while
Terminalia chebula and Withania somnifera (L.) dunal produced marked renal
lesions.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 4058035 [PubMed - indexed for MEDLINE]

189: Indian J Physiol Pharmacol. 1983 Apr-Jun;27(2):129-34.

Cardiovascular effects of a withanolide from Withania coagulans, dunal fruits.

Budhiraja RD, Sudhir S, Garg KN.

A new withanolide, with a unique chemical structure similar to the aglycones of
the cardiac glycosides, with mol. wt. 488 6, m. p. 260-261 degrees, isolated
from the fruits of Withania coagulans, was screened for cardiovascular effects.
At doses of 5 mg/kg body weight, the withanolide produced a moderate fall of
blood pressure in dogs (34 +/- 2.1, mm Hg) which was blocked by atropine and not
by mepyramine or propranolol. In rabbit Langendorff preparation and ECG studies,
it produced myocardial depressant effects but in perfused frog heart it produced
mild positive inotropic and chronotropic effects.

Publication Types:
In Vitro

PMID: 6885125 [PubMed - indexed for MEDLINE]

190: Biochem Med. 1983 Apr;29(2):259-64.

In vitro absorption of [14C]leucine during inflammation and the effect of
antiinflammatory drugs in the jejunum of rats.

Somasundaram S, Sadique J, Subramoniam A.

1. Inflammation was induced in the hindlegs of rats by formalin injection and
the in vitro absorption of [14C]leucine was studied. 2. Treatment of rats with
formalin caused a reduction in the in vitro absorption of leucine from the
mucosa of jejunum. 3. Oral administration of oxyphenbutazone or a herbal
anti-inflammatory drug (Withania somnifera) prior to formalin injection resulted
in no alteration in the jejunal absorption of [14C]leucine.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 6860324 [PubMed - indexed for MEDLINE]

191: Clin Exp Pharmacol Physiol. 1983 Mar-Apr;10(2):147-52.

Influence of extra-intestinal inflammation on the in vitro absorption of
14C-glucose and the effects of anti-inflammatory drugs in the jejunum of rats.

Somasundaram S, Sadique J, Subramoniam A.

Inflammation was induced in the hind legs of rats by formalin injection and the
in vitro jejunal absorption of 14C-glucose was studied. Treatment of rats with
formalin caused a reduction in the in vitro absorption of glucose from the
jejunum. Oral administration of oxyphenbutazone or a herbal anti-inflammatory
drug (Withania somnifera) prior to formalin injection, resulted in no alteration
in the jejunal absorption of glucose.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 6872332 [PubMed - indexed for MEDLINE]

192: Res Front Fertil Regul. 1982 Jun;2(1):1-16.

Current status of plant products reported to inhibit sperm.

Farnsworth NR, Waller DP.

PIP: This report reviews research on plant-derived agents that prevent sperm
production if taken orally by the male or that incapacitate or kill sperm on
contact if used vaginally by the female. It would be of great value to develop
fertility inhibitors that are totally selective for reproductive systems and
enzymes, and there is a possibility that a plant-derived drug may have this
effect. Plants that have been studied for their fertility inhibiting effects in
the male include: Aristolochia indica L. (Aristolochiaceae); Azadirachta indica
A. Juss (Meliaceae); Balanites roxburghii Planch. (Zygophyllaceae); Calotropis
procera (Ait) R.Br. (Asclepiadaceae); Carica papaya L. (Caricaceae);
Catharanthus roseus (L.) G. Don (Apocynaceae); Dieffenbachia seguine (Jacquin)
Schott. (Araceae); Ecaballium elaterium A. Richard (Cucurbitaceae); Gossypium
species (Malvaceae); Hibiscus rosa-sinensis L. (Malvaceae); Hippophae
salicifolia D. Don (Elaeagnaceae); Leucaena glauca (L.) Benth. (Leguminosae);
Lonicera ciliosa Poir. (Caprifoliaceae); Lupinus termis Forsk. (Leguminosae);
Malvaviscus conzattii Greenm. (Malvaceae); Momordica charantia L.
(Curcurbitaceae); Ocimum sanctum L. (Labiatae); Prunus emarginata Walp.
(Rosaceae); and Withania somnifera (L.) Dunal (Solanaceae). A large number of
plants have been randomly selected and screened for spermicidal activity "in
vitro" and several seem promising. Those species found to be active and the
nature of the active principle(s), when known, are presented in a table as are
plant-derived chemical substances of known or partially known structure reported
to be spermicidal "in vitro." Plants warrant systematic study as potential
sources of sperm-agglutinating compounds. Of 1600 Indian plants tested, 90
showed positive semen coagulating properties. There seems to be a lack of
correlation among experimental results obtained by different groups of
investigators, between data obtained "in vitro" and "in vivo," and between
experimental results and information found in folklore. Factors complicating
the adequate assessment of plants affecting male fertility are inadequate
numbers of vehicle-treated controls, poor experimental design, problems related
to insolubility of crude plant extracts, variation in routes of administration,
diversity in reproductive function and control among various laboratory species,
and problems in identifying plant names consistently.

PMID: 12179631 [PubMed - indexed for MEDLINE]

193: Indian J Exp Biol. 1981 Mar;19(3):245-9.

Influence of an Indian medicine (Ashwagandha) on acute-phase reactants in
inflammation.

Anbalagan K, Sadique J.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7251069 [PubMed - indexed for MEDLINE]

194: Planta Med. 1977 Sep;32(2):154-7.

Pharmacological investigations on fruits of Withania coagulans, Dunal.

Budhiraja RD, Bala S, Garg KN.

PMID: 905430 [PubMed - indexed for MEDLINE]

195: Planta Med. 1976 Nov;30(3):242-50.

[On the central effect of different Withania-extracts after oral applications to
animals (author's transl)]

[Article in German]

Fontaine R, Erdos A.

Publication Types:
English Abstract

PMID: 1005526 [PubMed - indexed for MEDLINE]

196: Lloydia. 1974 Dec;37(4):593-7.

A phytochemical investigation of Withania somnifera tissue cultures.

Yu Pl/El-Olemy MM/Stohs SJ.

PMID: 4453183 [PubMed - indexed for MEDLINE]

197: Planta Med. 1974 Nov;26(3):269-78.

[Morphology and anatomy of Indian roots of Withania somnifera (author's transl)]

[Article in German]

Menssen HG, Staesche K.

Publication Types:
English Abstract

PMID: 4427962 [PubMed - indexed for MEDLINE]

198: Experientia. 1974 Aug 15;30(8):852-3.

Variations in the antitumour constituents of withania somnifera dunal.

Chakraborti SK, De BK, Bandyopadhyay T.

PMID: 4416850 [PubMed - indexed for MEDLINE]

199: Planta Med. 1973 Aug;24(1):8-12.

[A C28-steroidlacton from the roots of Withania somnifera (author's transl)]

[Article in German]

Menssen HG, Stapel G.

PMID: 4779643 [PubMed - indexed for MEDLINE]

200: Eisei Shikenjo Hokoku. 1969;87:60-3.

[On the trial cultivation of Withania somnifera DUNAL. 3. Fertilizer experiment
of the three essential nutrients]

[Article in Japanese]

Kawatani T, Ono T.

PMID: 5392238 [PubMed - indexed for MEDLINE]

201: Indian J Physiol Pharmacol. 1968 Oct;12(4):175-81.

Studies on Withania ashwagandha Kaul. VI. The effect of the alkaloidal fractions
(acetone, alcohol and water soluble) on the central nervous system.

Prasad S, Malhotra CL.

PMID: 5737360 [PubMed - indexed for MEDLINE]

202: Eisei Shikenjo Hokoku. 1968;86:107-9.

[On the trial cultivation of Withania somnifera Dunal. II. Effect of sowing
season on the growth and root yield]

[Article in Japanese]

Kawatani T, Ono T.

PMID: 5753646 [PubMed - indexed for MEDLINE]

203: Eisei Shikenjo Hokoku. 1965 Oct;83:136-41.

[Trial cultivation of Withania somnifera Dunal]

[Article in Japanese]

Kawatani T, Ono T.

PMID: 5896382 [PubMed - indexed for MEDLINE]

204: Indian J Physiol Pharmacol. 1965 Jul;9(3):127-36.

Studies on Withania-ashwagandha, Kaul. V. The effect of total alkaloids
(ashwagandholine) on the central nervous system.

Malhotra CL, Mehta VL, Das PK, Dhalla NS.

PMID: 4957631 [PubMed - indexed for MEDLINE]

205: Indian J Physiol Pharmacol. 1965 Jan;9(1):9-15.

Studies on Withania ashwagandha, Kaul. IV. The effect of total alkaloids on the
smooth muscles.

Malhotra CL, Mehta VL, Prasad K, Das PK.

PMID: 5864885 [PubMed - indexed for MEDLINE]

206: Indian J Biochem. 1964 Sep;1(3):157-8.

Mechanism of antibacterial action of antibiotic isolated from leaves of Withania
somnifera. I. Reaction between the antibiotic & glutathione.

Das JM, Kurup PA.

PMID: 4243417 [PubMed - indexed for MEDLINE]

207: Arch Int Pharmacodyn Ther. 1964 Aug 1;150:356-62.

CARDIOTONIC ACTIVITY OF ASHWAGANDHINE AND ASHWAGANDHININE, TWO ALKALOIDS FROM
WITHANIA ASHWAGANDHA, KAUL.

DAS PK, MALHOTRA CL, PRASAD K.

PMID: 14203112 [PubMed - OLDMEDLINE]

208: J Pharm Sci. 1962 Dec;51:1194.

The occurrence of isopelletierine in Withania somnifera.

KHANNA KL, SCHWARTING AE, BOBBITT JM.

PMID: 14032282 [PubMed - indexed for MEDLINE]

209: Antibiot Chemother. 1962 Sep;12:576-82.

Comments on the activity of some constitutents of Withania somnifera Dun. I. The
antibacterial activity of five nitrogen-free substances isolated from the
leaves.

BEN-EFRAIM S, YARDEN A.

PMID: 13867009 [PubMed - indexed for MEDLINE]

210: Sven Farm Tidskr. 1962 Jun 30;6:481-90.

Phytochemical studies of the flora of Egypt. V. A comparative study of Withania
somnifera Dunal and Withania ashwagandha Kaul.

KHAFAGY S, EL-MOGHAZY AM, SANDBERG F.

PMID: 14455496 [PubMed - indexed for MEDLINE]

211: J Pharm Sci. 1961 Oct;50:876-7.

Chemical studies of the leaves of Withania somnifera.

DHALLA NS, SASTRY MS, MALHOTRA CL.

PMID: 13885950 [PubMed - indexed for MEDLINE]

212: Acta Physiol Pol. 1960 Sep-Dec;11:778-80.

[Chemotherapeutic properties of substances isolated from leaves of Withania
somnifera Dunal.]

[Article in Polish]

KOHLMUENZER S, KRUPINSKA J.

PMID: 13757589 [PubMed - indexed for MEDLINE]

213: Indian J Physiol Pharmacol. 1960 Jan;4:49-64.

Studies on Withania ashwagandha. (Part II): Effect of total extract on
cardiovascular system, respiration and skeletal muscle.

MALHOTRA CL, DAS PK, DHALLA NS.

PMID: 14420295 [PubMed - indexed for MEDLINE]

214: Indian J Physiol Pharmacol. 1960 Jan;4:35-48.

Studies on Withania ashwagandha. (Part I): Effect of total extract on central
nervous system and smooth muscles.

MALHOTRA CL, DAS PK, DHALLA NS.

PMID: 14420294 [PubMed - indexed for MEDLINE]

215: Arch Pharm Ber Dtsch Pharm Ges. 1956 Sep-Oct;289/61(9-10):604-8.

[Withania root as the falsification of Rauwolfia root.]

[Article in German]

LOGES W, NEUWALD F.

PMID: 13373367 [PubMed - indexed for MEDLINE]

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