Clinical Studies

Abstracts are presented below for clinical studies on Licorice.

  • Botanical Name: Glycyrrhiza Glabra

  • Ayurvedic Name: Yashtimadhu

  • Common Name: Licorice

Glycyrrhiza Glabra

Plant Phytonutrient Profile


1: Planta Med. 2007 Feb 28; [Epub ahead of print]

In Vitro and In Vivo Antiallergic Effects of Glycyrrhiza glabra and Its
Components.

Shin YW, Bae EA, Lee B, Lee SH, Kim JA, Kim YS, Kim DH.

College of Pharmacy, Kyung Hee University, Dongdaemun-ku, Seoul, Korea.

Licorice ( GLYCYRRHIZA GLABRA L., Leguminosae) is frequently used in traditional
medicine to treat inflammatory and allergic diseases. In this study, the main
components (glycyrrhizin, 18beta-glycyrrhetinic acid, isoliquiritin, and
liquiritigenin) were isolated from licorice, and their anti-allergic effects,
such as antiscratching behavior and IgE production-inhibitory activity, were
evaluated both IN VITRO and IN VIVO. Liquiritigenin and 18beta-glycyrrhetinic
acid most potently inhibited the degranulation of RBL-2H3 cells induced by IgE
with the antigen (DNP-HSA) and rat peritoneal mast cells induced by compound
48/80. Liquiritigenin and 18beta-glycyrrhetinic acid potently inhibited the
passive cutaneous anaphylactic reaction as well as the scratching behavior in
mice induced by compound 48/80. These components inhibited the production of IgE
in ovalbumin-induced asthma mice but liquiritigenin had little effect. This
suggests that the antiallergic effects of licorice are mainly due to
glycyrrhizin, 18beta-glycyrrhetinic acid, and liquiritigenin, which can relieve
IgE-induced allergic diseases such as dermatitis and asthma.

PMID: 17327992 [PubMed - as supplied by publisher]

2: J Altern Complement Med. 2007 Jan;13(1):103-10.

Antioxidant capacity of 55 medicinal herbs traditionally used to treat the
urinary system: a comparison using a sequential three-solvent extraction
process.

Wojcikowski K, Stevenson L, Leach D, Wohlmuth H, Gobe G.

Molecular and Cellular Pathology, School of Medicine, University of Queensland,
Brisbane, Queensland, Australia., Department of Natural and Complementary
Medicine, Southern Cross University, Lismore, NSW, Australia.

Background: The prevalence of chronic renal disease exceeds 10% in
industrialized societies. Oxidative damage is thought to be one of the main
mechanisms involved in nearly all chronic renal pathologies. Objective: We aimed
to use the oxygen radical absorbance capacity (ORAC) method and a sequential
multisolvent extraction process to compare the in vitro antioxidant capacity of
55 medicinal herbs and prioritize them for in vivo studies investigating the
value of herbal therapies in the treatment of renal disorders. Methods: The
herbs were chosen on the basis of their traditional use in kidney or urinary
system disorders, or because they have attracted the attention of recent
investigations into renal pathologies. The three solvents used for extraction
were ethyl acetate, methanol, and 50% aqueous methanol. Silybum marianum (milk
thistle) seed and Camellia sinensis (tea) leaf, both known to possess high
antioxidant capacity, were included for comparison. Results: Twelve of the 55
herbs were comparable to or exceeded ORAC levels of milk thistle seed or tea
leaf. The highest radical-scavenging activity was found in Olea europaea (olive
leaf), Cimicifuga racemosa (black cohosh), Rheum palmatum (rhubarb), Glycyrrhiza
glabra (licorice), and Scutellaria lateriflora (Virginia skullcap). Conclusions:
The antioxidant capacity of many of the herbs studied may, at least in part, be
responsible for their reputation as being protective of organs of the urinary
system. Overall, the combined ORAC values for the methanol and aqueous methanol
extracts comprised 84% of the total ORAC value. Sequential extraction with
solvents of different polarities may be necessary to fully extract the
antioxidant principles from medicinal plants.

PMID: 17309384 [PubMed - in process]

3: Drug Metab Dispos. 2007 Jan 12; [Epub ahead of print]

Role of P-glycoprotein in the Intestinal Absorption of Glabridin, An Active
Flavonoid from the Root of Glycyrrhiza glabra.

Cao J, Chen X, Liang J, Yu XQ, Xu AL, Chan E, Duan W, Huang M, Wen JY, Yu XY, Li
XT, Sheu FS, Zhou SF.

Department of General Surgery, the First Municipal Hospital of Guangzhou,
Guangzhou, China.

Glabridin is a major constituent of the root of Glycyrrhiza glabra, which is
commonly used in treatment of cardiovascular and central nervous system
diseases. This study aimed to investigate the role of P-glycoprotein (PgP/MDR1)
in the intestinal absorption of glabridin. The systemic bioavailability of
glabridin was about 7.5% in rats, but increased when combined with verapamil. In
single-pass perfused rat ileum with mesenteric vein cannulation, the
permeability coefficient of glabridin based on drug disappearance in luminal
perfusates (Plumen) was about 7-fold higher than that based on drug appearance
in the blood (Pblood). Glabridin was mainly metabolized by glucuronidation and
the metabolic capacity of intestine microsomes was 1/15 to 1/20 of that in liver
microsomes. Polarized transport of glabridin was found in Caco-2 and MDCKII
monolayers. Addition of verapamil in both apical (AP) and basolateral (BL) sides
abolished the polarized transport of glabridin across Caco-2 cells. Incubation
of verapamil significantly altered the intracellular accumulation and efflux of
glabridin in Caco-2 cells. The transport of glabridin in the BL-AP direction was
significantly higher in MDCKII cells overexpressing PgP/MDR1 than that in the
control cells. Glabridin inhibited PgP-mediated transport of digoxin with an
IC50 value of 2.56 microM, but stimulated PgP/MDR1 ATPase activity with a Km of
25.1 microM. The plasma AUC0-24h of glabridin in mdr1a(-/-) mice was 3.8-fold
higher than that in wildtype mice. These findings indicate that glabridin is a
substrate for PgP and both PgP/MDR1-mediated efflux and first-pass metabolism
contribute to the low oral bioavailability of glabridin.

PMID: 17220245 [PubMed - as supplied by publisher]

4: Mol Nutr Food Res. 2006 Nov;50(11):1080-6.

Hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (Linn) in
rats.

Visavadiya NP, Narasimhacharya AV.

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

The hypocholesterolaemic and antioxidant effects of Glycyrrhiza glabra (GG) root
powder were examined in hypercholesterolaemic male albino rats. A 4-week
administration of GG root powder (5 and 10 gm% in diet) to hypercholesterolaemic
rats resulted in significant reduction in plasma, hepatic total lipids,
cholesterol, triglycerides and plasma low-density lipoprotein and
VLDL-cholesterol accompanied by significant increases in HDL-cholesterol levels.
Furthermore, significant increases in fecal cholesterol, neutral sterols and
bile acid excretion along with an increase in hepatic HMG-CoA reductase activity
and bile acid production were observed in these animals. The root powder
administration to hypercholesterolaemic rats also decreased hepatic lipid
peroxidation with a concomitant increase in superoxide dismutase (SOD) and
catalase activities and total ascorbic acid content. Thus, the
hypocholesterolaemic and antioxidant effects of GG root appeared to be mediated
via (i) accelerated cholesterol, neutral sterol and bile acid elimination
through fecal matter with an increased hepatic bile acid production and (ii)
improving the activities of hepatic SOD, catalase and increasing the ascorbic
acid content. The normo-cholesterolaemic animals when fed with GG root powder at
10 gm% level, registered a significant decline in plasma lipid profiles and an
increase in HDL-cholesterol content. The antioxidant status of these animals
also was improved upon treatment.

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

PMID: 17054099 [PubMed - in process]

5: J Assoc Physicians India. 2006 May;54:400-2.

A young female with quadriparesis.

Mukherjee T, Bhatt K, Sirsat R.

Section of Nephrology, PD Hinduja National Hospital and Medical Research Centre,
Mahim, Mumbai 400 016.

We report a case of a young female who presented with acute onset quadriparesis
secondary to severe hypokalemia. She was normotensive and had no metabolic
alkalosis or kaliuresis. Serum potassium was corrected over the next few days
and the quadriparesis resolved completely. A detailed history later on revealed
that she had been consuming alternative medication for infertility for a
prolonged duration and had discontinued it a month prior. One of the ingredients
of this medicine was Glycyrrhiza glabra.

Publication Types:
Case Reports

PMID: 16909739 [PubMed - indexed for MEDLINE]

6: Int Immunopharmacol. 2006 Sep;6(9):1468-77. Epub 2006 Jun 6.

Glycyrrhizin alleviates experimental allergic asthma in mice.

Ram A, Mabalirajan U, Das M, Bhattacharya I, Dinda AK, Gangal SV, Ghosh B.

Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative
Biology, Mall Road, Delhi-110007, India.

Asthma is a chronic respiratory disease, the incidence of which is increasing
globally. The existing therapy is inadequate and has many adverse effects. It
needs a better therapeutic molecule preferably of natural origin, which has
negligible or no adverse effects. In view of this, we evaluated Glycyrrhizin
(GRZ), a major constituent of a plant Glycyrrhiza glabra, for its efficacy on
asthmatic features in a mouse model of asthma. BALB/c mice were sensitized and
challenged with ovalbumin (OVA) to develop the asthmatic features such as airway
hyperresponsiveness: allergen induced airway constriction and airway
hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation. The
mice were orally treated with GRZ (2.5, 5, 10 and 20 mg/kg) during or after
OVA-sensitization and OVA-challenge to evaluate its protective or reversal
effect, respectively on the above asthmatic features. The status of airway
hyperresponsiveness was measured by monitoring specific airway conductance
(SGaw) using a non-invasive method and the pulmonary inflammation was assessed
by haematoxylin and eosin staining of lung sections. Several other parameters
associated with asthma such as interleukin (IL)-4, IL-5 interferon-gamma
(IFN-gamma), OVA-specific IgE, total IgG(2a) and cortisol were measured by
ELISA. GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway
constriction, AHR to MCh (p<0.01), lung inflammation, and infiltration of
eosinophils in the peribronchial and perivascular areas. It prevented the
reduction of IFN-gamma (p<0.02), and decreased IL-4 (p<0.05), IL-5 (p<0.05) and
eosinophils (p<0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE
levels (p<0.01) and prevented the reduction of total IgG(2a) (p<0.01) in serum.
We have also showed that it has no effect on serum cortisol levels. Our results
demonstrate that GRZ alleviates asthmatic features in mice and it could be
useful towards developing a better therapeutic molecule in the future.

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

PMID: 16846841 [PubMed - indexed for MEDLINE]

7: J Med Food. 2006 Summer;9(2):281-3.

Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra,
Myristica fragrans, ascorbic acid, and metrifonate in mice.

Dhingra D, Parle M, Kulkarni SK.

Pharmacology Division, Department of Pharmaceutical Sciences, Guru Jambheshwar
University of Science and Technology, Hisar, Haryana, India.
[email protected]

The central cholinergic pathways play a prominent role in the learning and
memory processes. Acetylcholinesterase is an enzyme that inactivates
acetylcholine. The present study was undertaken to estimate the
acetylcholinesterase- inhibiting activity of extracts of Glycyrrhiza glabra,
Myristica fragrans seeds, and ascorbic acid and compare these values with a
standard acetylcholinesterase-inhibiting drug, metrifonate. Aqueous extract of
G. glabra (150 mg/kg p.o. for 7 successive days), n-hexane extract of M.
fragrans seeds (5 mg/kg p.o. for 3 successive days), ascorbic acid (60 mg/kg
i.p. for 3 successive days), and metrifonate (50 mg/kg i.p.) were administered
to young male Swiss albino mice. Acetylcholinesterase enzyme was estimated in
brains of mice. G. glabra, M. fragrans, ascorbic acid, and metrifonate
significantly decreased acetylcholinesterase activity as compared with their
respective vehicle-treated control groups.

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

PMID: 16822217 [PubMed - indexed for MEDLINE]

8: Phytother Res. 2006 Aug;20(8):687-95.

The effect of Echinacea purpurea, Astragalus membranaceus and Glycyrrhiza glabra
on CD69 expression and immune cell activation in humans.

Brush J, Mendenhall E, Guggenheim A, Chan T, Connelly E, Soumyanath A, Buresh R,
Barrett R, Zwickey H.

Helfgott Research Institute, National College of Naturopathic Medicine,
Portland, OR, USA.

The increasing use of medicinal herbs among the general public has piqued the
need for scientific-based research to determine the mechanism of action of herbs
administered orally in human subjects. The ability of three herbs, Echinacea
purpurea, Astragalus membranaceus and Glycyrrhiza glabra, to activate immune
cells in human subjects was assessed in this pilot study. The effect of these
herbs when ingested for 7 days was measured both when administered singly, and
in combination, using flow cytometry. The primary cell activation marker
measured was CD69. The results demonstrate that Echinacea, Astragalus and
Glycyrrhiza herbal tinctures stimulated immune cells as quantified by CD69
expression on CD4 and CD8 T cells. This activation took place within 24 h of
ingestion, and continued for at least 7 days. In addition, these three herbs had
an additive effect on CD69 expression when used in combination.

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

PMID: 16807880 [PubMed - indexed for MEDLINE]

9: Phytother Res. 2006 May;20(5):352-8.

Modulatory effects of several herbal extracts on avian peripheral blood cell
immune responses.

Dorhoi A, Dobrean V, Zahan M, Virag P.

Department of Infectious Diseases, Faculty of Veterinary Medicine, Cluj-Napoca,
Romania. [email protected]

Standardized ethanol extracts of Allium sativum (garlic), Glycyrrhiza glabra
(licorice), Plantago major (plantain) and Hippophae rhamnoides (sea buckthorn)
were assessed for their effects on cellular immunity in laying hens. Birds (n =
25) had blood samples taken and both specific and non-specific immune cell
responsiveness were evaluated by a leukocyte proliferation assay, carbon
clearance test and SRBC phagocytosis in monocyte-derived macrophage cultures.
Licorice and sea buckthorn (50 microg/mL) clearly enhanced the macrophage
membrane function (p < 0.05 and p < 0.01, respectively). Dual effects on
circulating phagocytes were revealed for plantain and sea buckthorn, while
garlic at 200 microg/mL impaired the phagocytic capacity of blood cells. None of
the tested extracts showed mitogenic properties, but high concentrations of sea
buckthorn (400 microg/mL) inhibited leukocyte proliferation. Small
concentrations (20 microg/mL) of licorice proved the co-mitogenic potential for
both T and B avian lymphocytes (p < 0.05). Certain extracts definitely enhanced
the fowl innate and/or specific cell immunity and may therefore improve host
resistance in poultry. Considering the chicken as an important non-mammalian
model that also serves as an available laboratory approach for some human
diseases, herbs exerting immunomodulatory properties may find relevant clinical
applications. Copyright 2006 John Wiley & Sons, Ltd.

PMID: 16619362 [PubMed - indexed for MEDLINE]

10: Pharmacol Res. 2006 Mar;53(3):303-9. Epub 2006 Feb 3.

Protective effects of isoliquiritigenin in transient middle cerebral artery
occlusion-induced focal cerebral ischemia in rats.

Zhan C, Yang J.

Department of Pharmacology, School of Medicine, Wuhan University, Donghu Road,
Wuhan 430071, China.

Epidemiological studies indicate that the intake of flavonoids is inversely
associated with risk of stroke, cardiovascular diseases and cancer.
Isoliquiritigenin (ISL), a flavonoid constituent in the root of Glycyrrhiza
glabra, is known to have vasorelaxant effect, antioxidant, anti-platelet,
anti-tumor, anti-allergic, antiviral activities and estrogenic properties.
However, there is no report on the effects of ISL in cerebral ischemia. Evidence
demonstrate that the impaired energy metabolism and the excessive generation of
reactive oxygen radicals (ROS) contribute to the brain injury associated with
cerebral ischemia. In the present study, the protective effects of ISL were
investigated in transient middle cerebral artery occlusion (MCAO)-induced focal
cerebral ischemia-reperfusion injury in rats. Male Sprague-Dawley rats were
divided into five groups: sham-operated group, vehicle-pretreated group, and
three ISL-pretreated groups (5, 10 and 20 mg kg(-1), i.g.). ISL were
administered once a day, for 7 days prior to ischemia. The rats were subjected
to 2 h right MCAO via the intraluminal filament technique and 22 h reperfusion.
Pretreatment with ISL significantly reduced the cerebral infarct volume and
edema and produced significant reduction in neurological deficits. In this
study, in order to clarify the mechanism of ISL's protection against cerebral
ischemia damage, cerebral energy metabolism, brain Na+K+ATPase activity,
malondialdehyde (MDA) content and antioxidant enzyme activities were measured.
ISL pretreatment increased the brain ATP content, energy charge (EC) and total
adenine nucleotides (TAN) in a dose-dependent manner. The brain Na+K+ATPase
activity was protected significantly by pretreatment of ISL for 7 days.
Pretreatment with ISL significantly inhibited the increases of brain MDA content
and prevented the activities of brain superoxide dismutase (SOD), catalase (CAT)
and glutathione peroxidase (GSH-Px) from declines caused by cerebral
ischemia-reperfusion. All these findings indicate that ISL has the protective
potential against cerebral ischemia injury and its protective effects may be due
to the amelioration of cerebral energy metabolism and its antioxidant property.

PMID: 16459097 [PubMed - indexed for MEDLINE]

11: Phytochem Anal. 2006 Jan-Feb;17(1):25-31.

Simultaneous HPLC analysis, with isocratic elution, of glycyrrhizin and
glycyrrhetic acid in liquorice roots and confectionery products.

Sabbioni C, Ferranti A, Bugamelli F, Forti GC, Raggi MA.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Alma Mater
Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Glycyrrhizin (1), the main active principle of Glycyrrhiza glabra (liquorice)
roots, is extensively used in herbal medicines, in pharmaceutical preparations
and confectionery products. A feasible and reliable method which allows the
simultaneous analysis of 1 and its aglycone, 18beta-glycyrrhetic acid (2), by
means of an isocratic HPLC procedure is described. The system uses a C8 column
as the stationary phase, and a mixture of acetonitrile, methanol, water and
glacial acetic acid as the mobile phase. Good linearity was found in the
concentration ranges 1-50 and 0.05-2.50 microg/mL for 1 and 2, respectively. A
simple and rapid sample pre-treatment, based on the extraction of the two
analytes with a mixture of water and ethanol, was developed for the examination
of liquorice confectionery products and root samples. The HPLC method was shown
to be appropriate, in terms of precision and feasibility, for the quality
control of the analytes in these matrices.

Publication Types:
Validation Studies

PMID: 16454473 [PubMed - indexed for MEDLINE]

12: Prog Neuropsychopharmacol Biol Psychiatry. 2006 May;30(3):449-54. Epub 2006
Jan 27.

Antidepressant-like activity of Glycyrrhiza glabra L. in mouse models of
immobility tests.

Dhingra D, Sharma A.

Pharmacology Division, Department Pharmaceutical Sciences, Guru Jambheshwar
University, Hisar-125001 (Haryana), India. [email protected]

The present study was undertaken to investigate the effects of aqueous extract
of Glycyrrhiza glabra L. (Family: Fabaceae), popularly known as liquorice, on
depression in mice using forced swim test (FST) and tail suspension test (TST).
The extract of G. glabra (75, 150, and 300 mg/kg) was administered orally for 7
successive days in separate groups of Swiss young male albino mice. The dose of
150 mg/kg of the extract significantly reduced the immobility times of mice in
both FST and TST, without any significant effect on locomotor activity of mice.
The efficacy of extract was found to be comparable to that of imipramine (15
mg/kg i.p.) and fluoxetine (20 mg/kg i.p.). Liquorice extract reversed
reserpine-induced extension of immobility period of mice in FST and TST.
Sulpiride (50 mg/kg i.p.; a selective D2 receptor antagonist) and prazosin (62.5
microg/kg i.p.; an alpha1-adrenoceptor antagonist) significantly attenuated the
extract-induced antidepressant-like effect in TST. On the other hand,
p-chlorophenylalanine (100 mg/kg i.p.; an inhibitor of serotonin synthesis) did
not reverse antidepressant-like effect of liquorice extract. This suggests that
antidepressant-like effect of liquorice extract seems to be mediated by increase
of brain norepinephrine and dopamine, but not by increase of serotonin.
Monoamine oxidase inhibiting effect of liquorice may be contributing favorably
to the antidepressant-like activity. Thus, it is concluded that liquorice
extract may possess an antidepressant-like effect.

Publication Types:
Comparative Study

PMID: 16443316 [PubMed - indexed for MEDLINE]

13: Int Immunopharmacol. 2006 Mar;6(3):494-8. Epub 2005 Aug 15.

Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites
tumor cells is inhibited by Glycyrrhiza glabra.

Sheela ML, Ramakrishna MK, Salimath BP.

Department of studies in Applied Botany and Biotechnology, University of Mysore,
Manasagangothri, Mysore-570 006, India.

Blood vessel plays a crucial role in solid tumor development. It has been
suggested that blocking of angiogenesis and the action of the cytokine VEGF
could be possible in cancer therapy. In a screen for naturally occurring
angiogenic inhibitors, we have identified an extract from the roots of
Glycyrrhiza glabra, which has potent antiangiogenic and antitumor activity. The
aqueous extract inhibits the in vivo and in vitro proliferation of Ehrlich
ascites tumor cells. The angioinhibitory activity of G. glabra was confirmed by
its inhibition of angiogenesis in in vivo assays, peritoneal and chorioallantoic
membrane assay. Reduction in the levels of the cytokine VEGF and microvessel
density count in the peritoneum of mice treated with G. glabra indicated that
the plant extract decreased VEGF production and the cytokine induced
neovascularization. Our results suggest that the extract from the roots of G.
glabra may be a potential supplemental source for cancer therapy.

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

PMID: 16428085 [PubMed - in process]

14: Cancer Lett. 2005 Dec 18;230(2):239-47.

Chemopreventive properties of the ethanol extract of chinese licorice
(Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in
MCF-7 human breast cancer cells.

Jo EH, Kim SH, Ra JC, Kim SR, Cho SD, Jung JW, Yang SR, Park JS, Hwang JW,
Aruoma OI, Kim TY, Lee YS, Kang KS.

Department of Veterinary Public Health, College of Veterinary Medicine, Seoul
National University, San 56-1, Shillim-Dong, Kwanak-gu, Seoul 151-742, South
Korea.

Much of the interest on the chemopreventive properties of licorice has been
focused on the plant genius Glycyrrhiza glabra. In this study the ethanol
extract of Chinese licorice root, Glycyrrhiza uralensis (G. uralensis) was
investigated for its estrogenic effect and the ability to inhibit cell
proliferation in the MCF-7 human breast cancer cell line. The extract of the
root of G. uralensis was fractionated in EtOH:H(2)O (80:20) (80% ethanol). The
extract exhibited estrogenic effects similar to 17beta- estradiol (E2) and
induced apoptosis at the same dose level (100 microg/ml) in MCF-7 breast cancer
cells, results were associated with up-regulation of tumor suppressor gene p53
and pro-apoptotic protein Bax. G. uralensis extract caused the up-regulation of
p21(waf1/cip1) and down-regulation of cdk 2 and cyclin E and most significantly,
induced G1 cell cycle arrest. This is the first study to show that the ethanolic
extract of the root of G. uralensis has an estrogen-like activity and
anti-cancer effects against MCF-7 human breast cancer cells. Whilst the use of
phytoestrogens to protect against hormone-dependent cancers or as a 'natural'
alternative to hormone replacement therapy remains controversial, the data in
this paper support the suggestion that extracts of root of the Chinese licorice
G. uralensis might be of importance in this debate.

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

PMID: 16297710 [PubMed - indexed for MEDLINE]

15: Bull Exp Biol Med. 2005 Aug;140(2):197-200.

Effect of licorice root on peripheral blood indexes upon vibration exposure.

Adamyan TI, Gevorkyan ES, Minasyan SM, Oganesyan KR, Kirakosyan KA.

Department of Human and Animal Physiology, Erevan State University, Erevan.
[email protected]

We studied the effect of continuous vibration and treatment with licorice root
(Glycyrrhiza glabra L.) on peripheral blood red cells in rabbits. Active
substances of licorice root accelerated metabolism in cells of the bone marrow
erythroid stem, enhanced compensatory reserve of the organism, and increased
animal's resistance to stress.

PMID: 16283000 [PubMed - indexed for MEDLINE]

16: J Biosci Bioeng. 2000;90(4):442-6.

Antifungal activity of plant extracts against Arthrinium sacchari and Chaetomium
funicola.

Sato J, Goto K, Nanjo F, Kawai S, Murata K.

Quality Assurance, Coca-Cola (Japan) Company, Limited, 6-3 Shibuya 4-chome,
Shibuya-ku, Tokyo 150-0002, Japan.

Various plant extracts were examined for antifungal activity with the objective
of improving the commercial sterility of aseptically filled tea beverage
products in PET bottles. When the hot water extract and the methanol extract of
29 samples were measured for their antifungal activity against Arthrinium
sacchari M001 and Chaetomium funicola M002 strains, five samples, Acer nikoense,
Glycyrrhiza glabra, Lagerstroemia speciosa, Psidium guajava and Thea sinensis,
showed high activity. Of these, the extracts from A. nikoense, G. glabra and T.
sinensis were fractionated by extraction with CHCl3, and the CHCl3-soluble
fractions from G. glabra showed antifungal activity with minimum inhibitory
concentrations (MICs) between 62.5 and 125 microg/ml against the above-mentioned
two fungi. When the EtOAc-soluble fraction of A. nikoense was used, the MIC
against A. sacchari M001 was 62.5 microg/ml. However, none of the fractions from
A. nikoense or T. sinensis showed high activity against C. funicola M002 and
their MICs were greater than 500 microg/ml. A licorice preparation made from the
commercially available oil-based extract of G. glabra showed a low MIC of 25
microg/ml against five tested strains of filamentous fungi, but not against
Aspergillus fumigatus M008, in a blended tea. Consequently, the possibility of
adding a licorice preparation made from the oil-based extract of G. glabra to
tea beverages (aseptically filled into PET bottles) was suggested.

PMID: 16232887 [PubMed]

17: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Dec 15;828(1-2):70-4.
Epub 2005 Sep 23.

Determination of glabridin in human plasma by solid-phase extraction and
LC-MS/MS.

Aoki F, Nakagawa K, Tanaka A, Matsuzaki K, Arai N, Mae T.

Research and Development Group, Functional Food Ingredients Division, Kaneka
Corporation, 1-8 Miyamae-machi, Takasago-cho, Takasago, Hyogo 676-8688, Japan.
[email protected]

Glabridin is a major flavonoid included specifically in licorice (Glycyrrhiza
glabra L.), and has various physiological activities including antioxidant and
anti-inflammatory effects. We have developed and validated an analytical method
for determination of glabridin in human plasma by solid-phase extraction (SPE)
and LC-MS/MS. Glabridin was extracted from plasma by SPE using a C8 cartridge
and analyzed by LC-MS/MS using mefenamic acid as an internal standard (IS). The
analyte were separated by a C18 column on LC, and monitored with a fragment ion
of m/z 201 formed from a molecular ion of m/z 323 for glabridin and that of m/z
196 from m/z 240 for IS during negative ion mode with tandem MS detection. The
lower limit of quantitation (LLOQ) of glabridin was 0.1 ng/mL in plasma,
corresponding to 1.25 pg injected on-column. The calibration curves exhibited
excellent linearity (r>0.997) between 0.1 and 50 ng/mL. Precision and accuracy
were <17 and <+/-7% at LLOQ, and <11 and <+/-5% at other concentrations.
Glabridin was recovered >90%, and was stable when kept at 10 degrees C for 72 h,
at -20 degrees C until 12 weeks, and after three freeze-thaw cycles. This is the
first report on determination of glabridin in body fluids by the selective,
sensitive, and reproducible method.

PMID: 16183339 [PubMed - indexed for MEDLINE]

18: Altern Med Rev. 2005 Sep;10(3):230-7.

Glycyrrhiza glabra. Monograph.

[No authors listed]

PMID: 16164378 [PubMed - indexed for MEDLINE]

19: Z Naturforsch [C]. 2005 Jul-Aug;60(7-8):649-56.

Binding of phytoestrogens to rat uterine estrogen receptors and human sex
hormone-binding globulins.

Hillerns PI, Zu Y, Fu YJ, Wink M.

Institut fur Pharmazie und Molekulare Biotechnologie, Universitat Heidelberg, Im
Neuenheimer Feld 364, 69120 Heidelberg, Germany.

The interaction of phytoestrogens with the most important binding sites of
steroid hormones, i.e. sex hormone-binding globulin and estrogen receptors, was
investigated. Relative binding affinities and association constants for 21
compounds among them isoflavones, flavones, flavonols, flavanones, chalcones and
lignans were determined. The lignan nordihydroguaiaretic acid weakly displaced
17beta-[3H]-estradiol from estrogen receptor and Scatchard analysis suggests
non-conformational changes. Compounds from Glycyrrhiza glabra, liquiritigenin
and isoliquiritigenin, showed estrogenic affinities to both receptors.
18beta-Glycyrrhetinic acid displaced 17beta-[3H]-estradiol from sex
hormone-binding globulin but not from the estrogen receptor. Phytoestrogens
compete with 17beta-estradiol much stronger than with 5alpha-dihydrotestosterone
for binding to sex hormone-binding globulin.

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

PMID: 16163844 [PubMed - indexed for MEDLINE]

20: J Environ Biol. 2005 Apr;26(2):169-73.

Allelopathic effects of weeds extracts against seed germination of some plants.

Kadioglu I, Yanar Y, Asav U.

Gaziosmanpasa University, Agricultural Faculty, 60250 Tokat, Turkey.
[email protected]

This study investigated the allelopathic effects of various weeds extracts on
seed germination of 11 crop species. Most of the weed extracts tested had
inhibitory effects on seed germination of common bean, tomato, pepper, squash,
onion, barley, wheat, and corn at different application rates as compared with
the 10% acetone control. Chickpea seed germination was inhibited by extracts of
Solanum nigrum L., Chenopodium album L., and Matricaria chamomilla L. (10%, 20%
and 22.5%, respectively) at the end of 21 day incubation period. However,
Glycyrrhiza glabra L., Sorghum halepense (L.) Pers., and Reseda lutea L.
extracts stimulated chickpea seed germination at the rates of 95%, 94%, and 93%,
respectively, compared to control. It was concluded that some of the weed
extracts tested in this study could be used as inhibitor while others could be
used as stimulator for the crops.

PMID: 16161968 [PubMed - indexed for MEDLINE]

21: J Asian Nat Prod Res. 2005 Aug;7(4):677-80.

Two new compounds from Glycyrrhiza glabra.

Li JR, Wang YQ, Deng ZZ.

Pharmaceutical Department, Medical College of the Chinese People Armed Police
Force, Tianjin 300162, China. [email protected]

Two new flavonosides have been isolated from the roots of Glychirriza glabra and
identified as 5,8-dihydroxy-flavone-7-O-beta-D-glucuronide, glychionide A, and
5-hydroxy-8-methoxyl-flavone-7-O-beta-D-glucuronide, glychionide B.

PMID: 16087644 [PubMed - indexed for MEDLINE]

22: J Nat Prod. 2005 Jul;68(7):1099-102.

Dihydrostilbene derivatives from Glycyrrhiza glabra leaves.

Biondi DM, Rocco C, Ruberto G.

Istituto del C.N.R. di Chimica Biomolecolare, Sezione di Catania, Via del
Santuario 110, I-95028 Valverde CT, Italy.

Four new dihydrostilbenes,
alpha,alpha'-dihydro-3,5-dihydroxy-4'-acetoxy-5'-isopentenylstilbene (1),
alpha,alpha'-dihydro-3,3',4'-trihydroxy-5-O-isopentenyl-6-isopentenylstilbene
(2), alpha,alpha'-dihydro-3,5,3'-trihydroxy-4'-methoxystilbene (3), and
alpha,alpha'-dihydro-3,3'-dihydroxy-5beta-d-O-glucopyranosyloxy-4'-methoxystilbe
ne (4), together with seven known flavonoids, glabranin isomer, naringenin,
lupiwighteone, pinocembrin 7-O-glucoside, astragalin, isoquercitrin, vicenin II,
and the inositol, pinitol, were isolated from the leaves of Glycyrrhiza glabra
grown in Sicily. The structures of 1-4 were elucidated by spectroscopic methods.

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

PMID: 16038558 [PubMed - indexed for MEDLINE]

23: J Chromatogr A. 2005 Jul 15;1081(1):65-71.

Separation and analysis of glycyrrhizin, 18beta-glycyrrhetic acid and
18alpha-glycyrrhetic acid in liquorice roots by means of capillary zone
electrophoresis.

Sabbioni C, Mandrioli R, Ferranti A, Bugamelli F, Saracino MA, Forti GC, Fanali
S, Raggi MA.

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Alma Mater
Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Glycyrrhizin is the main active compound of Glycyrrhiza glabra root extracts;
according to recent studies, glycyrrhizin and its aglycon, glycyrrhetic acid,
have interesting therapeutic properties. A new capillary electrophoretic method
has been developed for the separation and quantification of glycyrrhizin,
beta-glycyrrhetic acid and its isomer a-glycyrrhetic acid. Separation of the
analytes was achieved in less than 3 min on a fused silica capillary, by
injecting the samples at the short end of the capillary (effective length: 8.5
cm). The background electrolyte was composed of pH 10.0 carbonate buffer,
methanol and ethylene glycol (80/10/10) and contained 0.4% beta-cyclodextrin;
indomethacin was used as the internal standard. Diode array detection was used,
with quantitative assays carried out at 254 nm. Linearity was found over the
5-200 and 2.5-100 microg mL(-1) concentration ranges for glycyrrhizin and
glycyrrhetic acid, respectively. This method has been applied to the
determination of the analytes in different matrices (liquorice roots and
commercial confectionery products), and to the purity control of
beta-glycyrrhetic acid obtained from the hydrolysis of glycyrrhizin. When
analysing beta-glycyrrhetic acid and its epimer in roots, the samples were
purified by means of a suitable solid-phase extraction (SPE) procedure with
Oasis HLB cartridges, which granted good selectivity, eliminating matrix
interference.

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

PMID: 16013600 [PubMed - indexed for MEDLINE]

24: Roum Arch Microbiol Immunol. 2003 Jul-Dec;62(3-4):217-27.

Antioxidant properties of some hydroalcoholic plant extracts with
antiinflammatory activity.

Herold A, Cremer L, Calugaru A, Tamas V, Ionescu F, Manea S, Szegli G.

NIRDMI "Cantacuzino", Bucharest, Romania.

The hydroalcoholic extracts of Calendula officinalis, Hypericum perforatum,
Plantago lanceolata and Glycyrrhiza glabra which exhibited different
anti-inflammatory activities were evaluated for the possible mode of action by
studying their antioxidant potential. In the present study we investigated if
standardized hydroalcoholic extracts of plants such as Calendula officinalis,
Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra produced by
Hofigal Stock Company could modulate the respiratory burst of human activated
neutrophils, as a consequence of their antioxidant capacity. Their antioxidant
properties were measured using a colorimetric assay (Total Antioxidant Status
kit). We demonstrated that Hypericum perforatum and Calendula officinalis
hydroalcoholic extracts possessed a significant antioxidant activity while
Plantago lanceolata and Glycyrrhiza glabra hydroalcoholic extracts had a minor
antioxidant status. Using reactive oxygen species-generating systems
(OZ-activated human PMN neutrophils), Calendula officinalis and Hypericum
perforatum extracts showed strong reactive oxygen species scavenging property,
Hypericum perforatum extract exhibing the highest scavenging activity. These
results confirm the potential of Calendula officinalis and Hypericum perforatum
investigated hydroalcoholic extracts as medicinal remedies to be used in
different inflammatory/allergic diseases. These extracts could be a useful tool
for obtaining new antioxidant/anti-inflammatory agents.

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

PMID: 16008145 [PubMed - indexed for MEDLINE]

25: Chem Pharm Bull (Tokyo). 2005 Jul;53(7):847-9.

The isolation and structure elucidation of minor isoflavonoids from licorice of
Glycyrrhiza glabra origin.

Kinoshita T, Tamura Y, Mizutani K.

Faculty of Pharmaceutical Sciences, Teikyo University, Tsukui-gun, Kanagawa,
Japan. [email protected]

Two new isoflavanone and one new 3-arylcoumarin derivatives, along with a known
compound 3,4-didehydroglabridin, were isolated from commercially available
licorice of Glycyrrhiza glabra origin, and their structures were elucidated on
the basis of both the chemical and spectroscopic evidence.

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

PMID: 15997151 [PubMed - indexed for MEDLINE]

26: J Pharm Biomed Anal. 2005 Jul 15;38(4):594-600. Epub 2005 Mar 16.

Analysis and comparison of Radix Glycyrrhizae (licorice) from Europe and China
by capillary-zone electrophoresis (CZE).

Rauchensteiner F, Matsumura Y, Yamamoto Y, Yamaji S, Tani T.

Institute of Natural Medicine, Toyama Medical and Pharmaceutical University,
Japan. [email protected]

A simple capillary-zone electrophoresis (CZE) method for the analysis of plant
specimens, Glycyrrhiza glabra L., G. uralensisFisch. and G. inflata Bat.
(Leguminosae) as well as commercial licorices from Europe and China was
developed. Contents of glycyrrhizin (GL), glycyrrhetic acid (GA), glabridin
(GLAB), liquiritin (LQ) and licochalcone A (LC(A)) in ethanolic extracts were
investigated. Optimum separation was achieved with sodium tetraborate buffer (pH
9.22; 70 mM); voltage, 25 kV. Recovery rate for GL was found to be
101.90+/-2.54%. Adequate correlation was observed between GL contents measured
by CZE and HPLC (r=0.977). Advantages over conventional HPLC analysis of
Glycyrrhiza species are short analysis time (<15 min), simple running buffer
preparation and the none-use of organic solvents. Using the present CZE method,
it was demonstrated that (1) G. glabra was distinguished from G. uralensis
especially by phenolic compounds GLAB (G. glabra: 0.19+/-0.11%; n=53) and LQ (G.
uralensis, 1.34+/-0.34%, n=10); (2) on average, GL contents were higher in
Chinese commercial licorices; (3) relatively high LC(A) contents were especially
detected in a Chinese commercial licorice (origin estimated as G. inflata); (4)
Glycyrrhiza species were also distinguished by applying PCA on the basis of CZE
peak area data of GL, GLAB, GA, LQ and LC(A); and (5) liquiritin apioside was
found in all samples.

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

PMID: 15967286 [PubMed - indexed for MEDLINE]

27: Phytother Res. 2005 Mar;19(3):216-21.

Antioxidant activity of DHC-1, an herbal formulation, in experimentally-induced
cardiac and renal damage.

Bafna PA, Balaraman R.

Pharmacy Department, Faculty of Technology and Engineering, The M.S. University
of Baroda, Baroda -390 001, Gujarat, India.

DHC-1, an herbal formulation derived from the popular plants Bacopa monniera,
Emblica officinalis, Glycyrrhiza glabra, Mangifera indica and Syzygium
aromaticum was studied for its antioxidant activity. The protective effect of
DHC-1 in isoproterenol-induced myocardial infarction and cisplatin-induced renal
damage were studied. A significant reduction in the serum markers of heart and
kidney damage and the extent of lipid peroxidation with a concomitant increase
in the enzymatic (SOD and CAT) and non-enzymatic antioxidants (reduced
glutathione) were observed in DHC-1 pretreated animals compared with the
isoproterenol or cisplatin alone treated animals. Thus it can be concluded that
DHC-1 possesses a protective effect against both damaged heart and kidneys in
rats. This beneficial effect may be attributed, at least in part, to its
antioxidant activity. Copyright 2005 John Wiley & Sons, Ltd.

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

PMID: 15934019 [PubMed - indexed for MEDLINE]

28: Phytomedicine. 2005 Apr;12(4):264-70.

Anti-ulcer and anti-oxidant activity of pepticare, a herbomineral formulation.

Bafna PA, Balaraman R.

Department of Pharmacy, Faculty of Technology and Engineering, M.S. University
of Baroda, Kalabhavan, Baroda 390 001, Gujarat, India.

Pepticare, a herbomineral formulation of the Ayurveda medicine consisting of the
herbal drugs: Glycyrrhiza glabra, Emblica officinalis and Tinospora cordifolia,
was tested for its anti-ulcer and anti-oxidant activity in rats. Effects of
various doses (125, 250, 500 and 1000mg/kg, p.o.) of Pepticare were studied on
gastric secretion and gastric ulcers in pylorus-ligation and on ethanol-induced
gastric mucosal injury in rats. The reduction in ulcer index in both the models
along with the reduction in volume and total acidity, and an increase in the pH
of gastric fluid in pylorus-ligated rats proved the anti-ulcer activity of
Pepticare. It was also found that Pepticare was more potent than G. glabra alone
in protecting against pylorus-ligation and ethanol-induced ulcers. The increase
in the levels of superoxide dismutase, catalase, reduced glutathione and
membrane bound enzymes like Ca2+ ATPase, Mg2+ ATPase and Na+ K+ ATPase and
decrease in lipid peroxidation in both the models proved the anti-oxidant
activity of the formulation. Thus it can be concluded that Pepticare possesses
anti-ulcer activity, which can be attributed to its anti-oxidant mechanism of
action.

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

PMID: 15898703 [PubMed - indexed for MEDLINE]

29: Int J Low Extrem Wounds. 2003 Mar;2(1):25-39.

Plant medicines of Indian origin for wound healing activity: a review.

Biswas TK, Mukherjee B.

Department of Sharira Kriya, J. B. Roy State Ayurvedic Medical College and
Hospital.

Research on wound healing drugs is a developing area in modern biomedical
sciences. Scientists who are trying to develop newer drugs from natural
resources are looking toward the Ayurveda, the Indian traditional system of
medicine. Several drugs of plant, mineral, and animal origin are described in
the Ayurveda for their wound healing properties under the term Vranaropaka. Most
of these drugs are derived from plant origin. Some of these plants have been
screened scientifically for the evaluation of their wound healing activity in
different pharmacological models and patients, but the potential of most remains
unexplored. In a few cases, active chemical constituents were identified. Some
Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon,
Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa,
Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica,
Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental
models. This paper presents a limited review of plants used in Ayurvedic
medicine.

PMID: 15866825 [PubMed]

30: J Food Prot. 2005 Apr;68(4):773-7.

Microbiological quality of sous and tamarind, traditional drinks consumed in
Jordan.

Nassereddin RA, Yamani MI.

Department of Nutrition and Food Technology, Faculty of Agriculture, University
of Jordan, Amman, Jordan.

This study was conducted to evaluate the microbiological quality of sous (a
drink prepared by extracting dried roots of Glycyrrhiza glabra) and tamarind (a
drink prepared by infusing Tamarindus indica dried pulp), traditional drinks
consumed in Jordan. Twenty-one samples of sous and 44 samples of tamarind were
collected from the local market in Amman, Jordan. Water is the major component
of the drinks. Sous drink is characterized by having an alkaline pH (range, 6.6
to 9.9; mean, 8.6), whereas tamarind drink has an acidic pH (range, 1.8 to 3.7;
mean, 2.8). The drinks are not processed for safety before serving, and at some
vendors drinks are not properly refrigerated. The mean counts for aerobic
bacteria, lactic acid bacteria, and yeasts in sous drink samples were 5.9, 5.0,
and 3.8 log CFU/ml, respectively; those in tamarind drink samples were 4.0, <1,
and 5.8 log CFU/ml, respectively. The lactic acid bacteria isolated were
Enterococcus raffinosus, Enterococcus hirae, Enterococcus durans, Lactobacillus
acidophilus, and Lactobacillus buchneri. The yeast isolates in sous drink were
from the genera Candida, Filobasidium, Hanseniaspora, Lodderomyces, Pichia, and
Williopsis, and those in tamarind drink were from Arthroascus, Brettanomyces,
Candida, Debaromyces, Filobasidiella, Hanseniaspora, Klavispora, Lodderomyces,
Pichia, Saccharomycodes, Trichosporon, and Zygosaccharomyces. Enterobacteriaceae
were detected in two sous samples and were identified as Enterobacter sakazakii
and Erwinia sp., and in two tamarind samples and were identified as Citrobacter
freundii and Klebsiella pneumoniae. Salmonella was detected in one sous and one
tamarind sample. Pseudomonas aeruginosa was detected in only one sous sample.
These findings highlight the importance of application of hygienic practices
throughout preparation and vending of drinks, starting with raw ingredients and
continuing through preparation, storage, display, and serving.

PMID: 15830669 [PubMed - indexed for MEDLINE]

31: J Pharm Biomed Anal. 2005 Feb 23;37(2):287-95.

Assays of physical stability and antioxidant activity of a topical formulation
added with different plant extracts.

Di Mambro VM, Fonseca MJ.

Department of Pharmaceutical Science, Faculty of Pharmaceutical Sciences of
Ribeirao Preto, USP, Av. do Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil.
[email protected]

In the present investigation the changes on physical stability (pH, viscosity,
flow index and tixotropy) of topical formulations were evaluated following
inclusion of different plant extracts containing flavonoids. Also, the
antioxidant effect of these plant extracts alone and after addition in the
formulation was evaluated using chemiluminescence and the stable free radical
1,1-diphenyl-2-picrylhydrazyl (DPPH(.-)) assays, as well as the inhibition of
lipid peroxidation. Formulation added with dl-alpha-tocopherol was used to
compare the physical stability and antioxidant activity. Formulations with plant
extracts showed pseudoplastic behavior with decreasing on viscosity and
tixotropy. The Glycyrrhiza glabra (GG) and Ginkgo biloba (GB) extracts alone and
the formulations containing these extracts showed great antioxidant and free
radical scavenging activities while the other extracts studied (mixture of
Glycyrrhiza glabra, Symphytum officinale L and Arctium majus root, Nelumbium
speciosum and soybean) showed lower activity. The results suggest that GG and GB
extracts may be used in topical formulations in order to protect skin against
damage caused by free radical and reactive oxygen species.

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

PMID: 15708669 [PubMed - indexed for MEDLINE]

32: J Med Food. 2004 Winter;7(4):462-6.

Memory-strengthening activity of Glycyrrhiza glabra in exteroceptive and
interoceptive behavioral models.

Parle M, Dhingra D, Kulkarni SK.

Pharmacology Division, Department of Pharmaceutical Sciences, Guru Jambheshwar
University, Hisar, Haryana, India. [email protected]

In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza
glabra have been employed clinically for centuries for their anti-inflammatory,
anti-ulcer, expectorant, antimicrobial, and anxiolytic activities. The present
study was undertaken to investigate the effects of G. glabra, popularly known as
liquorice (Mulathi), on learning and memory. The elevated plus-maze and passive
avoidance paradigm were employed to evaluate learning and memory parameters.
Three doses (75, 150, and 300 mg/kg p.o.) of aqueous extract of G. glabra were
administered for 7 successive days in separate groups of mice. The dose of 150
mg/kg of the aqueous extract of liquorice significantly improved learning and
memory of mice. Furthermore, this dose reversed the amnesia induced by diazepam
(1 mg/kg i.p.), scopolamine (0.4 mg/kg i.p.), and ethanol (1 g/kg i.p.).
Anti-inflammatory and antioxidant properties of liquorice may be contributing
favorably to the memory enhancement effect. Since scopolamine-induced amnesia
was reversed by liquorice, it is possible that the beneficial effect on learning
and memory may be because of facilitation of cholinergic transmission in brain.
However, further studies are necessitated to identify the exact mechanism of
action. In the present investigation, G. glabra has shown promise as a memory
enhancer in both exteroceptive and interoceptive behavioral models of memory.

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

PMID: 15671690 [PubMed - indexed for MEDLINE]

33: Biol Pharm Bull. 2004 Nov;27(11):1775-8.

Licorice flavonoids suppress abdominal fat accumulation and increase in blood
glucose level in obese diabetic KK-A(y) mice.

Nakagawa K, Kishida H, Arai N, Nishiyama T, Mae T.

Functional Foods Development Division, Kaneka Corporation, Osaka, Japan.

Licorice, the root of the Glycyrrhiza species, is one of the most frequently
employed botanicals in traditional medicines. In this study, we investigated the
effects of hydrophobic flavonoids from Glycyrrhiza glabra LINNE on abdominal fat
accumulation and blood glucose level in obese diabetic KK-A(y) mice. In order to
enrich a fraction of hydrophobic flavonoids, licorice flavonoid oil (LFO) was
prepared by further extracting licorice ethanolic extract with medium-chain
triglycerides (MCT), and adjusting the concentration of glabridin, the major
flavonoid of licorice, to 1.2% in oil. KK-A(y) mice aged 6 weeks were assigned
to 5 groups (n=6 each), and fed a high-fat diet containing 0 (control), 0.5%,
1%, or 2% LFO, or 0.5% conjugated linoleic acid (CLA) for 4 weeks. Compared with
the control, body weight gain and weights of abdominal adipose tissues were
suppressed (p<0.05) by feeding the diet containing 2% LFO, and blood glucose
levels after 2 and 4 weeks were suppressed by all of the diets containing LFO.
Although CLA feeding suppressed (p<0.05) body weight gain, it increased (p<0.05)
blood glucose level after 2 weeks compared with the control level. Furthermore,
LFO and licorice ethanolic extract stimulated human adipocyte differentiation in
vitro. These results indicate that licorice hydrophobic flavonoids have
abdominal fat-lowering and hypoglycemic effects, possibly mediated via
activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma).

PMID: 15516721 [PubMed - indexed for MEDLINE]

34: Roum Arch Microbiol Immunol. 2003 Jan-Jun;62(1-2):117-29.

Hydroalcoholic plant extracts with anti-inflammatory activity.

Herold A, Cremer L, Calugaru A, Tamas V, Ionescu F, Manea S, Szegli G.

National Institute of Research-Developmentfor Microbiology and Immunology
Cantacuzino, Bucharest, Romania.

The aim of the present study was to investigate if standardized hydroalcoholic
plant extracts such as Calendula officinalis, Hypericum perforatum, Plantago
lanceolata and Glycyrrhiza glabra can suppress in cell-free systems the
activities of 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2), key enzymes in
the formation of proinflammatory eicosanoids from arachidonic acid (AA). Studies
were undertaken to compare the above mentioned plant extracts to a known NSAID
(nimesulide) in their ability to inhibit both cyclooxygenase (COX-2) and
lipoxygenase (5-LO) activities in cell-free systems. We report on 2 vegetal
extracts (Hypericum perforatum and Glycyrrhiza glabra) that inhibit 5-LO
activity and 2 vegetal extracts (Plantago lanceolata and Glycyrrhiza glabra)
that inhibit COX-2 activity. In this study, we demonstrate for the first time
that Glycyrrhiza glabra extract efficiently suppresses both eicosanoids and
leukotrienes formation in cell-free systems, implying that this extract directly
acts as a dual inhibitor of 5-LO and COX-2 activities. With regard to the
properties of dual COX-2/5-LO inhibitors, Glycyrrhiza glabra extract might be a
potential drug possessing anti-inflammatory activity devoid of the most
troublesome (gastric) side effects seen for drugs used as COX-2 and 5-LO
inhibitors. Hypericum perforatum, Plantago lanceolata and Glycyrrhiza glabra
extracts can be added to an already impressive list of these species that have
anti-inflammatory activity.

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

PMID: 15493372 [PubMed - indexed for MEDLINE]

35: Yakugaku Zasshi. 2004 Oct;124(10):705-9.

[Effects of nutrient solution concentration on inorganic and glycyrrhizin
contents of Glycyrrhiza glabra Linn]

[Article in Japanese]

Sato S, Ikeda H, Furukawa H, Murata Y, Tomoda M.

Faculty of Horticulture, Chiba University, Matsudo City 271-8510, Japan.
[email protected]

Licorice, Glycyrrhiza glabra Linn., is one of herbal medicines widely used for
various purposes, including as a sweetener and for gastric ulcer treatment.
However, environmental destruction due to the harvesting of wild licorice is
becoming a serious problem. We cultured licorice in a hydroponic system to
examine the relation between the concentration of nutritional solution applied
and glycyrrhizin content to determine the optimal nutrient solution
concentration for commercial licorice production. Licorice growth and
glycyrrhizin content in the root reached the highest values when the plants
received nutrient solution approximately equivalent to a quarter unit of
Hoagland solution. The results also indicated that the glycyrrhizin content does
not correlate with the concentration of nutrient solution applied and/or
inorganic contents absorbed, i.e., licorice may absorb large amounts of nutrient
solution but the glycyrrhizin content may not increase.

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

PMID: 15467279 [PubMed - indexed for MEDLINE]

36: Biol Pharm Bull. 2004 Oct;27(10):1691-3.

Oriental medicinal herb, Periploca sepium, extract inhibits growth and IL-6
production of human synovial fibroblast-like cells.

Tokiwa T, Harada K, Matsumura T, Tukiyama T.

Kohno Clinical Medicine Research Institute, Shinagawa-ku, Tokyo, Japan.
[email protected]

Periploca sepium (PS) has traditionally been used in oriental medicine for
treatment of rheumatoid arthritis (RA). We investigated the aqueous extract of
PS (PSE) in its effects on human rheumatoid arthritis-derived fibroblast-like
cells. In cell culture studies, PSE inhibited the growth and IL-6 production of
the cells in dose dependent manners. The extract of Glycyrrhiza glabra (GG),
which has also been used to treat RA and chosen as a reference here, slightly
inhibited the growth of RA cells. A study of PSE fractionation indicated that
the active material inhibiting IL-6 production is filterable by ultrafiltration,
suggesting that substances with low molecular weight might be involved in an
inhibition of IL-6 production. These results support the view that PSE
represents a rich source of growth inhibition and anti-IL 6 production.

Publication Types:
Comparative Study

PMID: 15467222 [PubMed - indexed for MEDLINE]

37: Fitoterapia. 2004 Sep;75(6):596-8.

Anticariogenic activity of some tropical medicinal plants against Streptococcus
mutans.

Hwang JK, Shim JS, Chung JY.

Department of Biotechnology and Bioproducts Research Center, Yonsei University,
Seoul 120-749, South Korea. [email protected]

The methanol extracts of five tropical plants, Baeckea frutescens, Glycyrrhiza
glabra, Kaempferia pandurata, Physalis angulata and Quercus infectoria,
exhibited potent antibacterial activity against the cariogenic bacterium
Streptococcus mutans. In particular, G. glabra, K. pandurata and P. angulata
conferred fast killing bactericidal effect against S. mutans in 2 min at 50
microg/ml of extract concentration.

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

PMID: 15351117 [PubMed - indexed for MEDLINE]

38: Biochem Biophys Res Commun. 2004 Sep 10;322(1):263-70.

Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza
glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate
cancer cells.

Fu Y, Hsieh TC, Guo J, Kunicki J, Lee MY, Darzynkiewicz Z, Wu JM.

Department of Biochemistry and Molecular Biology, New York Medical College,
Valhalla, NY 10595, USA.

Licochalcone (LA) is a novel estrogenic flavonoid isolated from PC-SPES
composition herb licorice root that was reported to show significant antitumor
activity in various malignant human cell lines. To better understand its
anti-CaP activities, we have investigated LA-elicited growth control and
induction of apoptosis using androgen-independent p53-null PC-3 prostate cancer
cells. LA induced modest level of apoptosis but had more pronounced effect on
cell cycle progression arresting cells in G2/M, accompanied by suppression of
cyclin B1 and cdc2. It also inhibited phosphorylation of Rb, specifically
phosphorylation of S780 with no change of phosphorylation status of T821,
decreased expression of transcription factor E2F concurrent with reduction of
cyclin D1, down-regulation of CDKs 4 and 6, but increased cyclin E expression.
These findings provide mechanistic explanation for LA activity and suggest that
it may be considered as a chemopreventive agent and its anticancer properties
should be further explored.

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

PMID: 15313200 [PubMed - indexed for MEDLINE]

39: Biol Pharm Bull. 2004 Jul;27(7):1086-92.

Differential expression of three oxidosqualene cyclase mRNAs in Glycyrrhiza
glabra.

Hayashi H, Huang P, Takada S, Obinata M, Inoue K, Shibuya M, Ebizuka Y.

Gifu Pharmaceutical University, Japan. [email protected]

The cultured cells and intact plants of Glycyrrhiza glabra (Fabaceae) produce
betulinic acid and oleanane-type triterpene saponins (soyasaponins and
glycyrrhizin). To elucidate the regulation of triterpenoid biosynthesis in G.
glabra, the cDNA of lupeol synthase, an oxidosqualene cyclase (OSC) responsible
for betulinic acid biosynthesis, was cloned, and expression patterns of lupeol
synthase and two additional OSCs, beta-amyrin synthase and cycloartenol
synthase, were compared. The mRNA expression levels of lupeol synthase and
beta-amyrin synthase were consistent with the accumulation of betulinic acid and
oleanane-type triterpene saponins, respectively. The transcript of lupeol
synthase was highly expressed in the cultured cells and root nodules. The
transcript of beta-amyrin synthase, an OSC responsible for oleanane-type
triterpene biosynthesis, was highly expressed in the cultured cells, root
nodules and germinating seeds, where soyasaponin accumulates, and in the
thickened roots where glycyrrhizin accumulates. In the cultured cells, the
addition of methyl jasmonate up-regulated beta-amyrin synthase mRNA and
soyasaponin biosynthesis, but down-regulated lupeol synthase mRNA. Furthermore,
the addition of gibberellin A(3) down-regulated beta-amyrin synthase mRNA but
not lupeol synthase mRNA in the cultured cells. The mRNA levels of cycloartenol
synthase, an additional OSC responsible for sterol biosynthesis, in the intact
plant and cultured cells were relatively constant in these experiments.

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

PMID: 15256745 [PubMed - indexed for MEDLINE]

40: Indian J Exp Biol. 2004 May;42(5):499-503.

Neuropharmacological actions of panchagavya formulation containing Emblica
officinalis Gaerth and Glycyrrhiza glabra Linn in mice.

Achliya GS, Wadodkar SG, Avinash KD.

Department of Pharmaceutical Sciences, Nagpur University, Amravati Road, Nagpur
440 033, India. [email protected]

A panchagavya Ayurvedic formulation containing E. officinalis, G. glabra, and
cow's ghee was evaluated for its effect on pentobarbital-induced sleeping time,
pentylenetetrazol-induced seizures, maximal electroshock-induced seizures,
spontaneous motor activity, rota-rod performance (motor coordination) and
antagonism to amphetamine in mice. The formulation (300, 500 mg/kg, po) produced
a significant prolongation of pentobarbital-induced sleeping time and reduced
spontaneous locomotor activity. The formulation also significantly antagonised
the amphetamine induced hyper-locomotor activity (500, 750 mg/kg, po) and
protected mice against tonic convulsions induced by maximal electroshock (500,
750 mg/kg, po). The formulation slightly prolonged the phases of seizure
activity but did not protect mice against lethality induced by
pentylenetetrazole. The formulation did not show neurotoxicity. The results
suggest that the panchagavya formulation is sedative in nature.

PMID: 15233476 [PubMed - indexed for MEDLINE]

41: Fitoterapia. 2004 Jun;75(3-4):371-4.

Variability in the content of active constituents and biological activity of
Glycyrrhiza glabra.

Statti GA, Tundis R, Sacchetti G, Muzzoli M, Bianchi A, Menichini F.

Dipartimento di Scienze Farmaceutiche, Universita degli Studi della Calabria,
via Pietro Bucci, I-87036 Arcavacata di Rende (CS), Italy.

Nine samples of Glycyrrhiza glabra were collected in various sites of Calabria,
Italy, with the aim to determine the variability in the confront of active
constituents and in antibacterial and antifungal activities of the extracts. The
samples showed remarkable differences in chemical composition and biological
activity. Copyright 2004 Elsevier B.V.

PMID: 15158998 [PubMed - indexed for MEDLINE]

42: J Hepatol. 2004 Mar;40(3):491-500.

Complementary and alternative therapies in the treatment of chronic hepatitis C:
a systematic review.

Coon JT, Ernst E.

Complementary Medicine, Peninsula Medical School, Universities of Exeter and
Plymouth, 25 Victoria Park Road, Exeter EX2 4NT, UK. [email protected]

BACKGROUND/AIMS: Hepatitis C is an escalating global health problem. The
recommended treatment regimen is associated with considerable expense, adverse
effects and poor efficacy in some patients. Complementary therapies are widely
promoted for and used by patients with hepatitis C. The aim is to systematically
assess the efficacy of complementary therapies in treating chronic hepatitis C.
METHODS: Systematic searches were conducted in six databases, reference lists of
all papers were checked for further relevant publications and information was
requested from experts. No language restrictions were imposed. RESULTS:
Twenty-seven eligible randomised clinical trials were located involving herbal
products and supplements. No randomised clinical trials were identified for any
other complementary therapy. In 14 of the trials, patients received
interferon-alpha in combination with the complementary therapy. Less than half
the trials (11/27) were of good methodological quality. Compared with the
control group, significant improvements in virological and/or biochemical
response were seen in trials of vitamin E, thymic extract, zinc, traditional
Chinese medicine, Glycyrrhiza glabra and oxymatrine. CONCLUSIONS: We identified
several promising complementary therapies, although extrapolation of the results
is difficult due to methodological limitations. More research is warranted to
establish the role of these and other therapies in the treatment of hepatitis C.

Publication Types:
Review

PMID: 15123365 [PubMed - indexed for MEDLINE]

43: J Ethnopharmacol. 2004 Apr;91(2-3):361-5.

Memory enhancing activity of Glycyrrhiza glabra in mice.

Dhingra D, Parle M, Kulkarni SK.

Pharmacology Division, Department of Pharmaceutical Sciences, P.O. Box 38, Guru
Jambheshwar University, Hisar 125001, Haryana, India. [email protected]

In the traditional system of medicine, the roots and rhizomes of Glycyrrhiza
glabra (family: Leguminosae) have been employed clinically for centuries for
their anti-inflammatory, antiulcer, expectorant, antimicrobial and anxiolytic
activities. The present study was undertaken to investigate the effects of
Glycyrrhiza glabra (popularly known as liquorice) on learning and memory in
mice. Elevated plus-maze and passive avoidance paradigm were employed to test
learning and memory. Three doses (75, 150 and 300 mg/kg p.o.) of aqueous extract
of Glycyrrhiza glabra were administered for 7 successive days in separate groups
of animals. The dose of 150 mg/kg of the aqueous extract of liquorice
significantly improved learning and memory of mice. Furthermore, this dose
significantly reversed the amnesia induced by diazepam (1 mg/kg i.p.) and
scopolamine (0.4 mg/kg i.p.). Anti-inflammatory and antioxidant properties of
liquorice may be contributing favorably to the memory enhancement effect. Since
scopolamine-induced amnesia was reversed by liquorice, it is possible that the
beneficial effect on learning and memory was due to facilitation of
cholinergic-transmission in mouse brain. However, further studies are
necessitated to identify the exact mechanism of action. In the present
investigation, Glycyrrhiza glabra has shown promise as a memory enhancing agent
in all the laboratory models employed.

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

PMID: 15120462 [PubMed - indexed for MEDLINE]

44: Integr Cancer Ther. 2003 Jun;2(2):120-38.

Phytoestrogens in botanical dietary supplements: implications for cancer.

Piersen CE.

UIC/NIH Center for Botanical Dietary Supplements Research in the Program for
Collaborative Research in the Pharmaceutical Sciences, University of Illinois at
Chicago, College of Pharmacy, 60612, USA. [email protected]

Phytoestrogens are plant constituents that possess either estrogenic or
antiestrogenic activity. Although their activities are weak as compared with
human endogenous estrogens, the consumption of phytoestrogens may have
clinically significant consequences. A number of botanicals, or the compounds
contained therein, have been identified as putative estrogenic agents, but
consensus in the biomedical community has been hampered by conflicting data from
various in vitro and in vivo models of estrogenic activity. Phytoestrogens may
serve as chemopreventive agents while at the same time being capable of
promoting growth in estrogen receptor positive cancer cell lines. Furthermore,
they may exert their estrogenic influence through receptor-dependent and/or
receptor-independent mechanisms. These findings have led to speculation that
phytoestrogen intake might be ill advised for patients at an increased risk for
hormone-dependent cancers, cancer patients, or cancer survivors. This article
will attempt to sort out discrepancies between various experimental models and
establish whether certain herbs possess estrogenic activity. The review will
focus on 5 popular botanical dietary supplements: Trifolium pratense (red
clover), Cimicifuga racemosa (black cohosh), Humulus lupulus (hops), Angelica
sinensis (dong quai), and Glycyrrhiza glabra (licorice). It will address their
mechanisms of action, clinical evidence bases, and implications for use in
cancer.

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

PMID: 15035899 [PubMed - indexed for MEDLINE]

45: Thromb Res. 2003;112(1-2):93-8.

Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor.

Mendes-Silva W, Assafim M, Ruta B, Monteiro RQ, Guimaraes JA, Zingali RB.

Departamento de Bioquimica Medica, Instituto de Ciencias Biomedicas, Centro de
Ciencias da Saude, Universidade Federal do Rio de Janeiro, 21941-590, Rio de
Janeiro, Brazil.

Glycyrrhizin (GL), an anti-inflammatory compound isolated from licorice
(Glycyrrhiza glabra), has been previously identified as a thrombin inhibitor
(Francischetti et al., Biochem Biophys Res Commun 1997;235:259-63). Here we
report the in vivo effects of GL upon two experimental models of induced
thrombosis in rats. Intravenous administration of GL caused a dose-dependent
reduction in thrombus size on a venous thrombosis model that combines stasis and
hypercoagulability. It was observed that GL doses of 180 mg/kg body weight
produced 93% decrease on thrombus weight. This effect showed a time-dependent
pattern being significantly reduced when the thrombogenic stimulus was applied
60 min after drug administration. GL was also able to prevent thrombosis using
an arteriovenous shunt model. GL doses of 180 and 360 mg/kg decreased the
thrombus weight by 35 and 90%, respectively. Accordingly, the APTT ex vivo was
enhanced by 1.5- and 4.3-fold at GL doses of 180 and 360 mg/kg, respectively. In
addition, GL doses above 90 mg/kg caused significant hemorrhagic effect. In
contrast with heparin, GL did not potentiate the inhibitory activity of
antithrombin III or heparin cofactor II towards thrombin. Altogether, data
indicate that GL is an effective thrombin inhibitor in vivo, which may account
for its other known pharmacological properties.

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

PMID: 15013279 [PubMed - indexed for MEDLINE]

46: J Cosmet Sci. 2003 Nov-Dec;54(6):551-8.

Comparison of antioxidant activity of extract from roots of licorice
(Glycyrrhiza glabra L.) to commercial antioxidants in 2% hydroquinone cream.

Morteza-Semnani K, Saeedi M, Shahnavaz B.

Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of
Medical Sciences, Sari, Iran.

Powdered dry roots of licorice (Glycyrrhiza glabra L.) were extracted with
methanol. Licorice extract was tested for antioxidative activity in comparison
with antioxidants (sodium metabisulfite and BHT) at 0.1%, 0.5%, 1.0%, and 2.0%
w/w in 2% w/w hydroquinone cream. The systems were incubated in a dark room at
25 degrees +/- 0.5 degrees C and 45 degrees +/- 0.5 degrees C for three months.
The physical stability and the percentages of hydroquinone remaining after two
weeks and one, two, and three months were determined by UV spectrophotometer at
294 nm according to official standard procedures. The experiment revealed that
oxidation degradation of hydroquinone was accelerated by heat even with the
existence of antioxidants. The higher percentages of remaining hydroquinone were
observed for higher antioxidant concentration but showed lower physical
stability in the formulation in the presence of commercial antioxidants,
especially in the cases of 1.0% and 2.0% BHT. In the third month, at 25 degrees
+/- 0.5 degrees C and 45 degrees +/- 0.5 degrees C, the extract demonstrated
more antioxidant activity from two other commercial antioxidants at all
concentrations, with about 43-53% and 34-46%, respectively, more hydroquinone
remaining than in the control system (p<0.001). In the third month, the
preparation containing 0.1%, 0.5%, 1.0%, and 2.0% extract gave good physical
formulation stability with about 72%, 76%, 78%, and 81 % hydroquinone remaining
at 25 degrees +/- 0.5 degrees C and 51%, 55%, 60%, and 63% hydroquinone
remaining at 45 degrees +/- 0.5 degrees C, respectively. This suggested the
possibility of using a licorice extract at 0.5% and 1.0% as an effective natural
antioxidant for substances that are oxidation-susceptible.

Publication Types:
Comparative Study

PMID: 14730371 [PubMed - indexed for MEDLINE]

47: Fitoterapia. 2003 Dec;74(7-8):624-9.

Preliminary evaluation of antinephritis and radical scavenging activities of
glabridin from Glycyrrhiza glabra.

Fukai T, Satoh K, Nomura T, Sakagami H.

Department of Physico-Chemical Analysis, School of Pharmaceutical Sciences, Toho
University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
[email protected]

Antinephritis activity of glabridin, a pyranoisoflavan isolated from Glycyrrhiza
glabra, was evaluated after its oral administration to mice with glomerular
disease (Masugi-nephritis) by measuring the urinary protein excretion, total
cholesterol, serum creatinine and blood urea nitrogen levels. Administration of
glabridin for 10 days (30 mg kg(-1) day(-1)) reduced the amount of urinary
protein excretion from control level (100+/-23 mg/day) to a significantly lower
level (47+/-4 mg/day). ESR spectroscopy demonstrated that glabridin neither
produced radical, nor affected the radical intensity of sodium ascorbate,
suggesting the lack of correlation between the antinephritis activity and
radical scavenging activity.

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

PMID: 14630165 [PubMed - indexed for MEDLINE]

48: Chem Pharm Bull (Tokyo). 2003 Nov;51(11):1338-40.

Field survey of Glycyrrhiza plants in Central Asia (3). Chemical
characterization of G. glabra collected in Uzbekistan.

Hayashi H, Hattori S, Inoue K, Khodzhimatov O, Ashurmetov O, Ito M, Honda G.

Gifu Pharmaceutical University, Mitahora-higashi, Gifu, Japan.
[email protected]

The chemical characteristics of Glycyrrhiza glabra L. were investigated at a
habitat in Uzbekistan. HPLC analysis of the underground parts indicated that
glycyrrhizin contents varied from 3.3 to 6.1% of dry weight, and that glabridin,
a species-specific flavonoid for G. glabra, was detected in all underground
samples (0.08-0.35% of dry weight). HPLC analysis of the leaves indicated that
G. glabra plants collected in the present study could be divided into two types,
RT-type and IQ-type, according to their major flavonol glycosides, rutin or
isoquercitrin, respectively.

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

PMID: 14600388 [PubMed - indexed for MEDLINE]

49: J Dermatolog Treat. 2003 Sep;14(3):153-7.

The treatment of atopic dermatitis with licorice gel.

Saeedi M, Morteza-Semnani K, Ghoreishi MR.

Department of Pharmaceutics, Mazandaran University of Medical Sciences, Sari,
Iran. [email protected]

Glycyrrhiza glabra L. has been used in herbal medicine for skin eruptions,
including dermatitis, eczema, pruritus and cysts. The effect of licorice extract
as topical preparation was evaluated on atopic dermatitis. The plant was
collected and extracted by percolation with suitable solvent. The extract was
standardized, based on Glycyrrhizinic acid by using a titrimetry method.
Different topical gels were formulated by using different co-solvents. After
standardizing of topical preparations, the best formulations (1% and 2%) were
studied in a double-blind clinical trial in comparison with base gel on atopic
dermatitis over two weeks (30 patients in each group). Propylene glycol was the
best co-solvent for the extract and Carbopol 940 as gelling agent showed the
best results in final formulations. The quantity of glycyrrhizinic acid was
determined 20.3% in the extract and 19.6% in the topical preparation. Two
percent licorice topical gel was more effective than 1% in reducing the scores
for erythema, oedema and itching over two weeks (p<0.05). The results showed
that licorice extract could be considered as an effective agent for treatment of
atopic dermatitis.

Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial

PMID: 14522625 [PubMed - indexed for MEDLINE]

50: Chem Pharm Bull (Tokyo). 2003 Oct;51(10):1147-52.

Field survey of Glycyrrhiza plants in central Asia (2). Characterization of
phenolics and their variation in the leaves of Glycyrrhiza plants collected in
Kazakhstan.

Hayashi H, Zhang SL, Nakaizumi T, Shimura K, Yamaguchi M, Inoue K, Sarsenbaev K,
Ito M, Honda G.

Gifu Pharmaceutical University, Japan. [email protected]

A new prenylated flavanone, licoleafol, and a new prenylated dihydrostilbene,
uralstilbene, together with four known compounds, 8-dimethylallyleriodictyol,
sophoraflavanone B, gancaonin R, and 6-dimethylallyleriodictyol, were isolated
from the leaves of Glycyrrhiza uralensis collected in Kazakhstan. HPLC analysis
of the leaves of Glycyrrhiza plants collected in Kazakhstan showed that both G.
uralensis-specific and Glycyrrhiza glabra-specific compounds were detected in
the leaves of the morphologically intermediate-type plants, suggesting that the
intermediate-type plant is a hybrid of G. glabra and G. uralensis. In addition,
HPLC profiles of leaf extracts from offspring of intermediate-type plants were
divided into the three types: the G. uralensis type, G. glabra type, and the
intermediate type. From these results, it appears likely that the
intermediate-type plant back-crosses with G. glabra and G. uralensis to generate
a G. glabra-type plant and a G. uralensis-type plant, respectively.

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

PMID: 14519919 [PubMed - indexed for MEDLINE]

51: Biosci Biotechnol Biochem. 2003 Aug;67(8):1629-35.

Small scale rat hepatocyte primary culture with applications for screening
hepatoprotective substances.

Nakagiri R, Oda H, Kamiya T.

Kyowa Hakko Kogyo Co., Ltd., Tsukuba Research Laboratories, 2 Miyukigaoka,
Tsukuba-shi, Ibaraki 305-0841, Japan. [email protected]

Isolated hepatocytes are known to maintain their physiological functions for
over a week when cultured on Matrigel, artificially reconstituted from basement
membrane components. Although this culture technique has been frequently used in
research on hepatocyte functions, there has been a limitation on its application
for small scale experiments due to some technical problems. By using
micro-culture plates with 96 round-bottom wells, we succeeded in coating the
wells uniformly with Matrigel. When the cultured hepatocytes were treated with
either 10 mM, 15 mM, or 20 mM of acetaminophen or 1 mM, 10 mM, or 20 mM of
D-galactosamine, the viability of the hepatocytes became 91.1%, 75.3%, 64.7%,
and 79.0%, 43.8%, 26.2% of the non-treated control at 48 hours, respectively.
Fractionated extracts of Glycyrrhiza glabra L. and Schisandra chinensis Baillon
inhibited the action of acetaminophen or D-galactosamine in this model. From
these results, we concluded that the microculture system presented here is
capable of maintaining the in vivo characteristics of hepatocytes and is
suitable for the screening of hepatoprotective substances.

PMID: 12951493 [PubMed - indexed for MEDLINE]

52: Yakugaku Zasshi. 2003 Aug;123(8):619-31.

[Pharmaceutical botanical studies on some Glycyrrhiza species]

[Article in Japanese]

Kusano G, Shibano M, Watanabe H, Ozaki K.

Osaka University of Pharmaceutical Sciences, a 4-20-1, Nasahara, Takatsuki
569-1094, Japan.

Some Glycyrrhiza species grown in several domestic research gardens of medicinal
plants were collected by the Osaka University of Pharmaceutical Sciences and
were cultivated to compare their morphological properties. HPLC profile analysis
was performed and index compounds of MeOH extracts of aerial parts and EtOAc
extracts of subterranean parts were determined. Glycyrrhizin contents and growth
rates of the underground parts of some types of Glycyrrhiza uralensis and
Glycyrrhiza glabra were compared and four excellent types were selected as
candidates for cultivation. One of them was due to Kanzo-Yashiki (Enzan,
Yamanashi prefecture), where G. uralensis was cultivated in the Edo period.
Alkaloidal constituents of G. uralensis and G. glabra were also investigated and
anabasine (an insecticide) and a new tricyclic alkaloid were obtained.

Publication Types:
English Abstract
Review

PMID: 12931658 [PubMed - indexed for MEDLINE]

53: Phytomedicine. 2003 May;10(4):271-85.

Double-blind, placebo-controlled, randomized, pilot clinical trial of
ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees,
with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and
Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

Amaryan G, Astvatsatryan V, Gabrielyan E, Panossian A, Panosyan V, Wikman G.

Republican Children's FMF Center, Yerevan State Medical University, Yerevan,
Armenia.

Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a
standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus
senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special
extracts standardized for the content of Andrographolide (4 mg/tablet),
Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel
groups of patients. The study was conducted in 24 (3-15 years of both genders)
patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets
of series A (verum) and 10 patients received series B product (placebo). The
study medication was taken three times of four tablets daily for 1 month. Daily
dose of the andrographolide--48 mg. The primary outcome measures in physician's
evaluation were related to duration, frequency and severity of attacks in FMF
patients (attacks characteristics score). The patient's self-evaluation was
based mainly on symptoms--abdominal, chest pains, temperature, arthritis,
myalgia, erysipelas-like erythema. All of 3 features (duration, frequency,
severity of attacks) showed significant improvement in the verum group as
compared with the placebo. In both clinical and self evaluation the severity of
attacks was found to show the most significant improvement in the verum group.
Both the clinical and laboratory results of the present phase II (pilot)
clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug
for the management of patients with FMF.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 12809357 [PubMed - indexed for MEDLINE]

54: J Ethnopharmacol. 2003 Jun;86(2-3):235-41.

Screening of traditionally used South African plants for antifungal activity
against Candida albicans.

Motsei ML, Lindsey KL, van Staden J, Jager AK.

Research Centre for Plant Growth and Development, School of Botany and Zoology,
University of Natal Pietermaritzburg, Private Bag X01, Scottsville 3209, South
Africa.

Twenty-four South African medicinal plants were screened against Candida
albicans standard strain ATCC 10231 and two clinical isolates from a 5-month-old
baby and an adult, in an attempt to find a traditional remedy to treat oral
candidiasis, which is prevalent in HIV-patients. Allium sativum L. and Tulbaghia
violacea L. aqueous bulb extracts had MIC values of 0.56 and 3.25mg/ml
respectively, whilst Polygala myrtifolia L. leaves and Glycyrrhiza glabra L.
rhizome extracts had MIC values of 1.56 mg/ml when tested against the
5-month-old isolate. Fresh water extracts stored at 4, 23 and 33 degrees C over
a period of a week, were used to determine the stability of these extracts.
Allium sativum and Tulbaghia violacea maintained activity at 4 degrees C, but
not at higher temperatures, whereas Polygala myrtifolia and Glycyrrhiza glabra
lost activity within a day even at 4 degrees C. The unpleasant taste of the two
species with a garlic smell, could however not be masked, and as the smell
following the eating of the two species would lead to HIV-patients being
recognised, these two plants where not considered for further investigation.
Therefore, Polygala myrtifolia and Glycyrrhiza glabra are being further
investigated for use as an oral mouthwash in clinics and homes.

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

PMID: 12738093 [PubMed - indexed for MEDLINE]

55: Plant Cell Physiol. 2003 Apr;44(4):404-11.

Up-regulation of soyasaponin biosynthesis by methyl jasmonate in cultured cells
of Glycyrrhiza glabra.

Hayashi H, Huang P, Inoue K.

Department of Pharmacognosy, Gifu Pharmaceutical University, Mitahora-higashi
5-6-1, Gifu, 502-8585 Japan. [email protected]

Exogenously applied methyl jasmonate (MeJA) stimulated soyasaponin biosynthesis
in cultured cells of Glycyrrhiza glabra (common licorice). mRNA level and enzyme
activity of beta-amyrin synthase (bAS), an oxidosqualene cyclase (OSC) situated
at the branching point for oleanane-type triterpene saponin biosynthesis, were
up-regulated by MeJA, whereas those of cycloartenol synthase, an OSC involved in
sterol biosynthesis, were relatively constant. Two mRNAs of squalene synthase
(SQS), an enzyme common to both triterpene and sterol biosyntheses, were also
up-regulated by MeJA. In addition, enzyme activity of UDP-glucuronic acid:
soyasapogenol B glucuronosyltransferase, an enzyme situated at a later step of
soyasaponin biosynthesis, was also up-regulated by MeJA. Accumulations of bAS
and two SQS mRNAs were not transient but lasted for 7 d after exposure to MeJA,
resulting in the high-level accumulation (more than 2% of dry weight cells) of
soyasaponins in cultured licorice cells. In contrast, bAS and SQS mRNAs were
coordinately down-regulated by yeast extract, and mRNA accumulation of
polyketide reductase, an enzyme involved in 5-deoxyflavonoid biosynthesis in
cultured licorice cells, was induced transiently by yeast extract and MeJA,
respectively.

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

PMID: 12721381 [PubMed - indexed for MEDLINE]

56: J Nat Prod. 2003 Apr;66(4):477-80.

New dihydrostilbene derivatives from the leaves of Glycyrrhiza glabra and
evaluation of their antioxidant activity.

Biondi DM, Rocco C, Ruberto G.

Istituto del CNR di Chimica Biomolecolare, Sezione di Catania, Via del Santuario
110, I-95028 Valverde CT, Italy.

Five new prenylated dihydrostilbenes,
alpha,alpha'-dihydro-3,5,4'-trihydroxy-4,5'-diisopentenylstilbene (1),
alpha,alpha'-dihydro-3,5,3',4'-tetrahydroxy-4,5'-diisopentenylstilbene (2),
alpha,alpha'-dihydro-3,5,4'-trihydroxy-5'-isopentenylstilbene (3),
alpha,alpha'-dihydro-3,5,3'-trihydroxy-4'-methoxy-5'-isopentenylstilbene (4),
and alpha,alpha'-dihydro-3,5,3',4'-tetrahydroxy-5'-isopentenyl stilbene (5),
along with four known flavonoids, glabranin (6), pinocembrin, (7), licoflavone
(8), and wighteone (9), were isolated from a lipid extract of the leaves of
Sicilian Glycyrrhiza glabra. The structures of the compounds were elucidated by
spectroscopic methods. The antioxidant activities of the crude extracts and the
isolated compounds were tested.

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

PMID: 12713396 [PubMed - indexed for MEDLINE]

57: Eur Urol. 2003 May;43(5):580-6.

Isoliquiritigenin inhibits the growth of prostate cancer.

Kanazawa M, Satomi Y, Mizutani Y, Ukimura O, Kawauchi A, Sakai T, Baba M,
Okuyama T, Nishino H, Miki T.

Department of Urology, Kyoto Prefectural University of Medicine,
Kawaramachi-Hirokoji, Kyoto 602-8566, Japan. [email protected]

OBJECTIVE: Isoliquiritigenin, one of the components in the root of Glycyrrhiza
glabra L., is a member of the flavonoids, which are known to have an anti-tumor
activity in vitro and in vivo. In this study, we investigated the anti-tumor
effect of isoliquiritigenin on prostate cancer in vitro.METHODS: DU145 and LNCaP
prostate cancer cell lines were used as targets. We examined the effects of
isoliquiritigenin on cell proliferation, cell cycle regulation and cell
cycle-regulating gene expression. Further, we investigated the effects of
isoliquiritigenin on the GADD153 mRNA and protein expression, and promoter
activity.RESULTS: Isoliquiritigenin significantly inhibited the proliferation of
prostate cancer cell lines in a dose-dependent and time-dependent manner.
Fluorescence-activated cell sorting (FACS) analysis indicated that
isoliquiritigenin induced S and G2/M phase arrest. Isoliquiritigenin enhanced
the expression of GADD153 mRNA and protein associated with cell cycle arrest.
Further, isoliquiritigenin stimulated transcriptional activity of GADD153
promoter dose-dependently.CONCLUSION: These findings suggest that
isoliquiritigenin is a candidate agent for the treatment of prostate cancer and
GADD153 may play an important role in isoliquiritigenin-induced cell cycle
arrest and cell growth inhibition.

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

PMID: 12706007 [PubMed - indexed for MEDLINE]

58: Phytochemistry. 2003 May;63(1):97-104.

Comparative antioxidant activity of individual herbal components used in
Ayurvedic medicine.

Naik GH, Priyadarsini KI, Satav JG, Banavalikar MM, Sohoni DP, Biyani MK, Mohan
H.

Radiation Chemistry and Chemical Dynamics Division, Bhabha Atomic Research
Centre, Trombay, Mumbai-400085, India.

Four aqueous extracts from different parts of medicinal plants used in Ayurveda
(an ancient Indian Medicine) viz., Momardica charantia Linn (AP1), Glycyrrhiza
glabra (AP2), Acacia catechu (AP3), and Terminalia chebula (AP4) were examined
for their potential as antioxidants. The antioxidant activity of these extracts
was tested by studying the inhibition of radiation induced lipid peroxidation in
rat liver microsomes at different doses in the range of 100-600 Gy as estimated
by thiobarbituric acid reactive substances (TBARS). Of all these extracts, AP4
showed maximum inhibition in the TBARS formation and hence is considered the
best antioxidant among these four extracts. The extracts were found to restore
antioxidant enzyme superoxide dismutase (SOD) from the radiation induced damage.
The antioxidant capacities were also evaluated in terms of ascorbate equivalents
by different methods such as cyclic voltammetry, decay of ABTS(.-) radical by
pulse radiolysis and decrease in the absorbance of DPPH radicals. The results
were found to be in agreement with the lipid peroxidation data and AP4 showed
maximum value of ascorbate equivalents. Therefore AP4, with high antioxidant
activity, is considered as the best among these four extracts.

Publication Types:
Comparative Study

PMID: 12657303 [PubMed - indexed for MEDLINE]

59: Skin Pharmacol Appl Skin Physiol. 2003 Mar-Apr;16(2):84-90.

Anti-acne effects of Oriental herb extracts: a novel screening method to select
anti-acne agents.

Nam C, Kim S, Sim Y, Chang I.

Skin Reserach Institute, Pacific R&D Center, Yongin, Korea. [email protected]

The acne-therapeutic effects of Oriental herb extracts were investigated in
terms of antichemotactic effect on polymorphonuclear leucocytes, antilipogenic
actions, antibacterial activity against Propionibacterium acnes and resistance
induction potency in the bacteria. The ethanol extract (0.01%) of Angelica
dahurica markedly suppressed neutrophil chemotaxis, comparable to the effect of
erythromycin (0.01%), whereas a strong antilipogenic effect was obtained with
rhizoma coptidis (Coptis chinensis) extract (0.01%), leading to a higher
efficacy than that of retinoic acid (0.01%). Interestingly, only Glycyrrhiza
glabra showed a remarkable antibacterial activity against P. acnes, resulting in
negligible induction of resistance, in comparison with a marked development of
resistance in the bacteria treated with erythromycin. We suggest that an
appropriate formulation containing A. dahurica, rhizoma coptidis and G. glabra
could be helpful for the prevention and treatment of acne lesions. Copyright
2003 S. Karger AG, Basel

Publication Types:
Comparative Study

PMID: 12637783 [PubMed - indexed for MEDLINE]

60: Phytomedicine. 2002 Dec;9(8):757-62.

A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used
for women's health.

Xu H, Fabricant DS, Piersen CE, Bolton JL, Pezzuto JM, Fong H, Totura S,
Farnsworth NR, Constantinou AI.

UIC/NIH Center for Botanical Dietary Supplements Research, University of
Illinois at Chicago, Chicago, Illinois, USA.

Traditional taxonomic methods of botanical identification that rely primarily on
morphological observations cannot be used efficiently when only powdered plant
materials are available. Thus, our objectives were to determine if we could
apply a molecular approach to: a) produce unique DNA profiles that are
characteristic of the species, and b) determine if the geographical area or time
of collection influences these DNA profiles. Towards this end, random amplified
polymorphic DNA (RAPD) analyses were performed on a number of botanicals
currently used for women's health. The test materials included samples from
three species each of the genera Cimicifuga (Actaea) and Trifolium, as well as
samples of Vitex agnus-castus L., Glycyrrhiza glabra L., Gingko biloba L.,
Valeriana officinalis L., Angelica sinensis (Oliv.) Diels, Viburnum prunifolium
L., Humulus lupulus L., Vaccinium macrocarpon Ait., Panax ginseng C.A. Mey.
Cimicifuga racemosa (L.) Nutt. and Trifolium pratense L. are currently under
clinical investigation in our basic research laboratories and medical clinic for
the relief of post-menopausal symptoms. Characteristic profiles produced with
the OPC-15 primer could distinguish the three Cimicifuga species: C. racemosa,
C. americana and C. rubifolia. Similar results were obtained with the three
Trifolium species: Trifolium pratense L., Trifolium incarnatum L., and Trifolium
repens L. Accessions of cultivated T. pratense collected from the same field at
different times, produced identical profiles. Accessions of Cimicifuga species
collected from different geographical areas produced similar but not identical
DNA profiles; however, species-specific DNA fragments were identified. These
results demonstrate that RAPD analysis can be applied to distinguish species
when only powdered material is available for testing. This methodology can be
applied to identify species of commercial value regardless of collection time or
geographic area.

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

PMID: 12587700 [PubMed - indexed for MEDLINE]

61: Curr Med Chem. 2003 Jan;10(2):155-71.

Chemical modification of glycyrrhizic acid as a route to new bioactive compounds
for medicine.

Baltina LA.

Institute of Organic Chemistry Ufa Research Centre of RAS, 71 Prospect
Oktyabrya, Ufa, 450054, Russian Federation. [email protected]

Glycyrrhizic Acid (GL) is the major bioactive triterpene glycoside of licorice
root (Glycyrrhiza Radix) extracts possessing a wide range of pharmacological
properties (anti-inflammatory, anti-ulcer, anti-allergic, anti-dote,
anti-oxidant, anti-tumor, anti-viral etc.). Official sources of GL are
Glycyrrhiza glabra L. and Gl. uralensis Fish. (Leguminosae). The content of GL
in licorice root is 2-24% of the dry weight. GL is one of the leading natural
compounds for clinical trials of chronic active viral hepatitis and HIV
infections (preparation Stronger Neo-Minophagen C, SNMC), and its monoammonium
salt (glycyram, tussilinar) is used as an anti-inflammatory and anti-allergic
remedy. The synthetic transformations of GL on carboxyl and hydroxyl groups were
carried out to produce new bioactive derivatives for medicine. GL esters were
produced containing fragments of bioactive acids (4-nitrobenzoic, cinnamic,
salycilic, acetylsalycilic, nicotinic, isonicotinic). Bioactive amides of GL
were synthesized using chloroanhydride technique and
N,N'-diciclohexylcarbodiimide (DCC) method. The synthesis of acylthioureids and
semicarbazones was carried out via the reaction of triacylisothiocianate of
penta-O-acetyl-GL with primary amines and hydrazines. The chain of
transformations of trichloranhydride of penta-O-acetyl-GL was made with the
introduction of diazoketone groups in the molecule. A new group of GL
derivatives to be triterpene glycopeptides was prepared by the activated esters
method (N-hydrohysuccinimide-DCC or N-hydroxybenzotriazol-DCC) using alkyl
(methyl, ethyl, propyl, butyl, tert-butyl) or benzyl (4-nitrobenzyl) esters of
amino acids. The glycyrrhizyl analogs of the known immunostimulator,
N-acetyl-muramoyldipeptide (MDP), were synthesized using Reagent Woodward K. A
series of ureids and carbamates of GL was synthesized containing
5-amino-5-desoxy-D-xylopyranose units. The synthesis of
4-nitro-4-desoxy-glycosides, modified analogs of GL, was carried out by the
oxidative splitting of the carbohydrate part of GL with NaIO(4). Triterpene
2-desoxy-D-glycosides, analogs of GL, were prepared by the glycal method in the
presence of iodine-containing promoters or sulfonic acid cation-exchange resin
KU-2-8 (H+) and LiBr. New anti-inflammatory and anti-ulcer agents were found
among GL derivatives such as esters, amides, ureids, carbamates, thioureids and
glycopeptides. GL glycopeptides are of interest as immunomodulators. Some of the
chemically modified GL derivatives (salts, amides, glycopeptides) were potent
HIV-1 and HIV-2 inhibitors in vitro. Preparation niglizin (penta-O-nicotinate of
GL) was studied clinically as an anti-inflammatory agent and is of interest for
studies as hepatoprotector and HIV inhibitor.

Publication Types:
Review

PMID: 12570715 [PubMed - indexed for MEDLINE]

62: Eur J Cancer Prev. 2002 Aug;11 Suppl 2:S8-11.

Plant antimutagens and their mixtures in inhibition of genotoxic effects of
xenobiotics and aging processes.

Alekperov UK.

Institute of Genetics, 155 Prospect Azadliq, 370106, Baku, Azerbaijan Republic.

The antimutagenic effect of the bioactive compounds from fruits of Morus alba L.
(MA), Punica granatum L. (PG), Diospyros kaki L. (DK), Cydonia oblonga Mill.
(CO) and roots of Glycyrrhiza glabra (GG) were investigated. The antimutagenic
effects of compounds separately as well as their action in complex mixtures were
studied on mutations induced by genotoxicants (X-rays, N-methylnitrosourea,
cyclophosphamide, NaF) and aging in bone marrow cell chromosomes from mice and
rats. When tested separately and in a complex mixture, the plant products showed
an ability to decrease the frequency of chromosome aberrations. The
antimutagenic properties of the complex mixtures were considerably greater than
those of the separate components. More antimutagenic activity of the mixture was
revealed when mutagenesis was the result of X-rays and the natural aging
processes.

Publication Types:
Comparative Study

PMID: 12570329 [PubMed - indexed for MEDLINE]

63: Farmaco. 2002 Nov;57(11):883-8.

The effect of glycyrrhizin on the release rate and skin penetration of
diclofenac sodium from topical formulations.

Nokhodchi A, Nazemiyeh H, Ghafourian T, Hassan-Zadeh D, Valizadeh H, Bahary LA.

Department of Pharmacy, School of Health and Life Sciences, Franklin-Wilkins
Building, 150 Stamford Street, London SE1 9NN, UK. [email protected]

The influence of glycyrrhizin extracted from Glycyrrhiza glabra var.
glandulifera (licorice roots) on the percutaneous absorption of diclofenac
sodium from sodium carboxymethylcellulose (NaCMC) gels or oil-in-water (o/w)
emulsion was investigated. Skin permeation experiments were carried out using
excised abdominal rat skin. The results showed that the efficiency of
glycyrrhizin as an enhancer agent is greater in gel formulations than it is in
the emulsions. The enhancer with the concentration of 0.1% w/w in gel increased
diclofenac sodium flux value to tenfold compared with the control gel.

PMID: 12484536 [PubMed - indexed for MEDLINE]

64: J Gastroenterol Hepatol. 2002 Dec;17 Suppl 3:S370-S376.

Herbal medicines for liver diseases in India.

Thyagarajan S, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi M.

The use of natural remedies for the treatment of liver diseases has a long
history, starting with the Ayurvedhic treatment, and extending to the Chinese,
European and other systems of traditional medicines. The 21st century has seen a
paradigm shift towards therapeutic evaluation of herbal products in liver
diseases by carefully synergizing the strengths of the traditional systems of
medicine with that of the modern concept of evidence-based medicinal evaluation,
standardization of herbal products and randomized placebo controlled clinical
trials to support clinical efficacy. The present review provides the status
report on the scientific approaches made to herbal preparations used in Indian
systems of medicine for the treatment of liver diseases. In spite of the
availability of more than 300 preparations for the treatment of jaundice and
chronic liver diseases in Indian systems of medicine using more than 87 Indian
medicinal plants, only four terrestrial plants have been scientifically
elucidated while adhering to the internationally acceptable scientific
protocols. In-depth studies have proved Sylibum marianum to be anti-oxidative,
antilipidperoxidative, antifibrotic, anti-inflammatory, immunomodulating and
liver regenerative. Glycyrrhiza glabra has been shown to be hepatoprotective and
capable of inducing an indigenous interferon. Picrorhiza kurroa is proved to be
anti-inflammatory, hepatoprotective and immunomodulatory. Extensive studies on
Phyllanthus amarus have confirmed this plant preparation as being anti-viral
against hepatitis B and C viruses, hepatoprotective and immunomodulating, as
well as possessing anti-inflammatory properties. For the first time in the
Indian systems of medicine, a chemo-biological fingerprinting methodology for
standardization of P. amarus preparation has been patented. Copyright 2002
Blackwell Publishing Asia Pty Ltd

PMID: 12472966 [PubMed - as supplied by publisher]

65: Bull Exp Biol Med. 2002 Aug;134(2):135-6.

Antioxidant effect of licorice root on blood catalase activity in vibration
stress.

Oganesyan KR.

Department of Human and Animal Physiology, Erevan State University, Armenia.

Rabbits were treated (orally) with a preparation of Glycyrrhiza glabra L. for 30
days and in parallel were exposed to vibration stress (30 days). The licorice
preparation reduced catalase activity in the peripheral blood and increased
animal resistance to vibration stress.

PMID: 12459833 [PubMed - indexed for MEDLINE]

66: Food Chem Toxicol. 2002 Oct;40(10):1525-7.

Liquorice (Glycyrrhiza glabra) and the adrenal-kidney-pituitary axis in rats.

Al-Qarawi AA, Abdel-Rahman HA, Ali BH, El Mougy SA.

The effect of oral administration of a water freeze-dried extract of Glycyrrhiza
glabra (liquorice) has been studied at doses of 100, 250 and 500 mg/kg in rats
on the plasma concentration of cortisol, adrenocorticotrophic hormone (ACTH),
aldosterone, renin, sodium (Na) and potassium (K). The results indicated that
treatment induced dose-dependent and mostly significant decreases in the
concentration of cortisol, ACTH, aldosterone and K. There were concomitant
dose-dependent increases in the concentrations of renin and Na. The results
suggest a strong and dose-dependent suppression of the adrenal-pituitary axis,
accompanied by stimulation of renin production from the kidney.

PMID: 12387318 [PubMed - indexed for MEDLINE]

67: Fitoterapia. 2002 Oct;73(6):536-9.

Antimicrobial activity of licorice flavonoids against methicillin-resistant
Staphylococcus aureus.

Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T.

School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi,
Chiba 274-8510, Japan. [email protected]

Nineteen flavonoids isolated from licorice (Glycyrrhiza glabra, G. inflata and
G. uralensis) were tested for their antimicrobial activities against methicillin
sensitive Staphylococcus aureus, methicillin resistant S. aureus, Micrococcus
luteus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and
Pseudomonas aeruginosa. Copyright 2002 Elsevier Science B.V.

PMID: 12385884 [PubMed - indexed for MEDLINE]

68: Phytother Res. 2002 Sep;16(6):576-8.

Protection of DNA and microsomal membranes in vitro by Glycyrrhiza glabra L.
against gamma irradiation.

Shetty TK, Satav JG, Nair CK.

Radiation Biology Division, Bhabha Atomic Research Centre, Mumbai 400 085,
India.

The radioprotective effect of the root extract of Glycyrrhiza glabra L on lipid
peroxidation in rat liver microsomes and plasmid pBR322 DNA was investigated.
The extract was found to protect microsomal membranes, as evident from reduction
in lipid peroxidation, and could also protect plasmid DNA from radiation-induced
strand breaks. Copyright 2002 John Wiley & Sons, Ltd.

Publication Types:
In Vitro

PMID: 12237818 [PubMed - indexed for MEDLINE]

69: Phytomedicine. 2002 Jul;9(5):390-7.

Immunological studies of Revitonil, a phytopharmaceutical containing Echinacea
purpurea and Glycyrrhiza glabra root extract.

Wagner H, Jurcic K.

Department of Pharmacy, Center of Pharma Research, Institut of Pharmaceutical
Biology, University of Munich, Germany. [email protected]

A phytopharmaceutical containing an extract of Echinacea purpurea and
Glycyrrhiza glabra root (Revitonil tablets) was investigated for its suggested
immunostimulating potential, using several in vitro tests and the in vivo
carbon-clearance model in mice. In the in vitro phagocytosis test with human
granulocytes, Revitonil showed a 44-53% stimulating effect at a concentration of
100 microg/ml. Whereas in the chemoluminescence test at a concentration of 1.25
microg/ml, Revitonil tablets exhibited a moderate enhancing effect only, a
remarkable stimulating activity (30-50%) was observed in the T-lymphocyte CD69
bioassay at a concentration of 100 microg-1 microg/ml. The highest immunological
efficacy could be assigned to Revitonil as revealed by the in vivo
carbon-clearance model in mice. With RCt/RCc-values of 2.0, Revitonil exhibited
a very high carbon elimination rate at oral administration. Because the
Echinacea and Glycyrrhiza monoextracts alone showed lower RCt/RCc-values
(1.3-1.7) than Revitonil, a potentiating synergistic effect of the extract
mixture in Revitonil can be postulated.

Publication Types:
Comparative Study
In Vitro

PMID: 12222657 [PubMed - indexed for MEDLINE]

70: Life Sci. 2002 Aug 9;71(12):1449-63.

Anti-Helicobacter pylori flavonoids from licorice extract.

Fukai T, Marumo A, Kaitou K, Kanda T, Terada S, Nomura T.

Department of Physico-chemical Analysis, School of Pharmaceutical Sciences, Toho
University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
[email protected]

Licorice is the most used crude drug in Kampo medicines (traditional Chinese
medicines modified in Japan). The extract of the medicinal plant is also used as
the basis of anti-ulcer medicines for treatment of peptic ulcer. Among the
chemical constituents of the plant, glabridin and glabrene (components of
Glycyrrhiza glabra), licochalcone A (G. inflata), licoricidin and licoisoflavone
B (G. uralensis) exhibited inhibitory activity against the growth of
Helicobacter pylori in vitro. These flavonoids also showed anti-H. pylori
activity against a clarithromycin (CLAR) and amoxicillin (AMOX)-resistant
strain. We also investigated the methanol extract of G. uralensis. From the
extract, three new isoflavonoids (3-arylcoumarin, pterocarpan, and isoflavan)
with a pyran ring, gancaonols A[bond]C, were isolated together with 15 known
flavonoids. Among these compounds, vestitol, licoricone, 1-methoxyphaseollidin
and gancaonol C exhibited anti-H. pylori activity against the CLAR and
AMOX-resistant strain as well as four CLAR (AMOX)-sensitive strains. Glycyrin,
formononetin, isolicoflavonol, glyasperin D, 6,8-diprenylorobol, gancaonin I,
dihydrolicoisoflavone A, and gancaonol B possessed weaker anti-H. pylori
activity. These compounds may be useful chemopreventive agents for peptic ulcer
or gastric cancer in H. pylori-infected individuals.

PMID: 12127165 [PubMed - indexed for MEDLINE]

71: Acta Pharm Hung. 2001 Oct;71(3):325-8.

[Comparative study of Glycyrrhiza glabra L. and Glycyrrhiza echinata L. of
different origin. Medicinal plant polysaccharides III]

[Article in Hungarian]

Gyemant G, Lenkey B, Nanasi P.

Debreceni Egyetem, Termeszettudomanyi Kar, Biokemiai Tanszek, Debrecen.

Comparative study was carried out among the polysaccharides of Chinese,
Lithuanian and Hungarian origin Glycyrrhiza glabra L. as well as the Hungarian
origin Glycyrrhiza echinata L. Monosaccharide composition, measured as alditol
acetates, of Chinese and Hungarian G. glabra was very similar, but the
Lithuanian G. glabra and the G. echinata were quite different. The
monosaccharides of polysaccharides isolated from root and stem of G. echinata
show significant differences (Table II.). All investigated samples contain
glucuronic acid, the G. echinata contains also galacturonic acid (Table II.).
Some fractions with higher uronic acid content and the acidic polysaccharides
isolated from these fractions were studied and their monosaccharide composition
was determined (Table III. and IV.).

Publication Types:
Comparative Study
English Abstract

PMID: 11961901 [PubMed - indexed for MEDLINE]

72: Eur J Biochem. 2001 Dec;268(23):6311-7.

Molecular cloning and characterization of isomultiflorenol synthase, a new
triterpene synthase from Luffa cylindrica, involved in biosynthesis of bryonolic
acid.

Hayashi H, Huang P, Inoue K, Hiraoka N, Ikeshiro Y, Yazaki K, Tanaka S, Kushiro
T, Shibuya M, Ebizuka Y.

Gifu Pharmaceutical University, Japan. [email protected]

An oxidosqualene cyclase cDNA, LcIMS1, was isolated from cultured cells of Luffa
cylindrica Roem. by heterologous hybridization with cDNA of Glycyrrhiza glabra
beta-amyrin synthase. Expression of LcIMS1 in yeast lacking endogenous
oxidosqualene cyclase activity resulted in the accumulation of isomultiflorenol,
a triterpene. This is consistent with LcIMS1 encoding isomultiflorenol synthase,
an oxidosqualene cyclase involved in bryonolic acid biosynthesis in cultured
Luffa cells. The deduced amino-acid sequence of LcIMS1 shows relatively low
identity with other triterpene synthases, suggesting that isomultiflorenol
synthase should be classified into a new group of triterpene synthases. The
levels of isomultiflorenol synthase and cycloartenol synthase mRNAs, which were
measured with gene-specific probes, correlated with the accumulation of
bryonolic acid and phytosterols over a growth cycle of the Luffa cell cultures.
Isomultiflorenol synthase mRNA was low during the early stages of cell growth
and accumulated to relatively high levels in the late stages. Induction of this
mRNA preceded accumulation of bryonolic acid. In contrast, cycloartenol synthase
mRNA accumulated in the early stages of the culture cycle, whereas phytosterols
accumulated at the same relative rate throughout the whole growth cycle. These
results suggest independent regulation of these two genes and of the
accumulation of bryonolic acid and phytosterols.

PMID: 11733028 [PubMed - indexed for MEDLINE]

73: Bioorg Khim. 2000 Nov;26(11):873-6.

[Glabrizoflavone--a novel isoflavone from Glycyrrhiza glabra L.]

[Article in Russian]

Iuldashev MP, Batirov EKh, Vdovin AD, Abdullaev ND.

Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of
Uzbekistan, prosp. Akademika Abdullaeva 77, Tashkent, 700170 Uzbekistan.

7-O-Methylglabranin, 6-C-prenylpinocembrin, glabranin, pinocembrin, galangin,
and a novel isoflavonoid,
(E)-5,7,4'-trihydroxy-6-(3-hydroxymethyl-2-butenyl)isoflavone (glabrisoflavone)
were isolated from the aerial parts of Glycyrrhiza glabra L. The structure of
the novel isoflavonoid was elucidated on the basis of chemical transformations
and spectral data.

Publication Types:
English Abstract

PMID: 11696898 [PubMed - indexed for MEDLINE]

74: Phytomedicine. 2001 Sep;8(5):401-9.

Synergy and other interactions in phytomedicines.

Williamson EM.

The School of Pharmacy, University of London, United Kingdom.
[email protected]

Synergistic interactions are of vital importance in phytomedicines, to explain
difficulties in always isolating a single active ingredient, and explain the
efficacy of apparently low doses of active constituents in a herbal product.
This concept, that a whole or partially purified extract of a plant offers
advantages over a single isolated ingredient, also underpins the philosophy of
herbal medicine. Evidence to support the occurrence of synergy in within
phytomedicines is now accumulating and is reviewed here. Synergistic
interactions are documented for constituents within a total extract of a single
herb, as well as between different herbs in a formulation. Positive and negative
aspects of interactions are discussed together with the methods used to identify
and measure synergy. The evidence is divided into experimental, in vitro
instances, as well as clinical examples where available. Herbs discussed include
Ginkgo biloba, Piper methysticum (Kava-Kava), Glycyrrhiza glabra, Hypericum
perforatum, Valeriana officinalis, Cannabis sativa, Salix alba and others.

Publication Types:
Review

PMID: 11695885 [PubMed - indexed for MEDLINE]

75: Exp Mol Med. 2001 Sep 30;33(3):131-5.

Stimulation of melanogenesis by glycyrrhizin in B16 melanoma cells.

Jung GD, Yang JY, Song ES, Par JW.

Department of Dermatology, Presbyterian Medical Center, Chonju, Korea.

Glycyrrhizin (GR), triterpenoid saponin composed of one glycyrrhetinic acid (GA)
and two glucuronic acids, is a main constituent of the hydrophilic fraction of
licorice (Glycyrrhiza glabra) extracts and is known to have a wide range of
pharmacological actions. In this study, we investigated the mechanism of GR
effect on melanogenesis in B16 murine melanoma cells. The cellular levels of
tyrosinase mRNA, protein, enzyme activities and melanin contents were increased
by GR in a dose dependent manner. Expression of tyrosinase-related protein-2
(TRP-2) mRNA was also increased by GR, however, no significant change was
observed on TRP-1. No cytotoxicity was observed at the effective concentration
range of GR. GA showed no effect on melanogenesis at the equivalent nontoxic
concentrations, indicating that glycoside structure is important in the
stimulatory effect of GR on melanogenesis. These results indicate that
GR-induced stimulation of melanogenesis is likely to occur through the
transcriptional activation.

PMID: 11642548 [PubMed - indexed for MEDLINE]

76: Biol Pharm Bull. 2001 Aug;24(8):912-6.

Cloning and characterization of a cDNA encoding beta-amyrin synthase involved in
glycyrrhizin and soyasaponin biosyntheses in licorice.

Hayashi H, Huang P, Kirakosyan A, Inoue K, Hiraoka N, Ikeshiro Y, Kushiro T,
Shibuya M, Ebizuka Y.

Gifu Pharmaceutical University, Japan. [email protected]

An oxidosqualene cyclase cDNA, termed GgbAS1, was isolated from cultured cells
of licorice (Glycyrrhiza glabra) by heterologous hybridization with cDNA of
Arabidopsis thaliana LUP1 lupeol synthase. The yeast transformed with an
expression vector containing the open reading frame of GgbAS1 produced
beta-amyrin, indicating that GgbAS1 encodes beta-amyrin synthase involved in the
glycyrrhizin and soyasaponin biosyntheses in licorice. Northern blot analysis
showed that the level of beta-amyrin synthase mRNA was drastically changed in
the cultured licorice cells, whereas the mRNA level of cycloartenol synthase was
relatively constant.

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

PMID: 11510484 [PubMed - indexed for MEDLINE]

77: Arzneimittelforschung. 2001;51(7):545-53.

Antiulcerogenic effect of some gastrointestinally acting plant extracts and
their combination.

Khayyal MT, el-Ghazaly MA, Kenawy SA, Seif-el-Nasr M, Mahran LG, Kafafi YA,
Okpanyi SN.

Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita,
Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica,
Silybum marianum and Chelidonium majus, singly and combined in the form of a
commercial preparation, STW 5 (Iberogast) and a modified formulation, STW 5-II,
lacking the last 3 constituents, were tested for their potential
anti-ulcerogenic activity against indometacin induced gastric ulcers of the rat
as well as for their antisecretory and cytoprotective activities. All extracts
produced a dose dependent anti-ulcerogenic activity associated with a reduced
acid output and an increased mucin secretion, an increase in prostaglandin E2
release and a decrease in leukotrienes. The effect on pepsin content was rather
variable and did not seem to bear a relationship with the anti-ulcerogenic
activity. The most beneficial effects were observed with the combined
formulations STW 5 and STW 5-II in a dose of 10 ml/kg b.w., comparable with
cimetidine in a dose of 100 mg/kg b.w. The anti-ulcerogenic activity of the
extracts was also confirmed histologically. The cytoprotective effect of the
extracts could be partly due to their flavonoid content and to their free
radical scavenging properties.

PMID: 11505785 [PubMed - indexed for MEDLINE]

78: Biosci Biotechnol Biochem. 2001 Apr;65(4):853-60.

Increases of secondary metabolite production in various plant cell cultures by
co-cultivation with cork.

Yamamoto H, Yato A, Yazaki K, Hayashi H, Taguchi G, Inoue K.

Medicinal Plant Garden, School of Pharmaceutical Sciences, Nagasaki University,
Japan.

Cork tissues increased secondary metabolite production of various plant cell
cultures in a different manner from those of conventional elicitors. In Sophora
flavescens and Glycyrrhiza glabra cultured cells, cork tissues increased the
amounts of both lipophilic and hydrophilic flavonoids without affecting the cell
growth, although elicitors such as copper ion and yeast extracts showed a clear
inhibition of cell growth with the increasing amount of these lipophilic ones.
The validity of this effect of cork tissues covered a wide range of aromatic
compounds produced by suspension cell cultures derived from diverse plant
species. Woody tissues of Japanese cypress had a very similar effect to that of
cork. Partial purification of cork tissues suggested that the
production-stimulating factor was present in the hemicellulose B fraction that
was not included in the dedifferentiated cultured tissues.

PMID: 11388464 [PubMed - indexed for MEDLINE]

79: J Agric Food Chem. 2001 May;49(5):2472-9.

Evaluation of estrogenic activity of plant extracts for the potential treatment
of menopausal symptoms.

Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, Booth N, Constantinou
AI, Pezzuto JM, Fong HH, Farnsworth NR, Bolton JL.

Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for
Botanical Dietary Supplements Research, College of Pharmacy, M/C 781, University
of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA.

Eight botanical preparations that are commonly used for the treatment of
menopausal symptoms were tested for estrogenic activity. Methanol extracts of
red clover (Trifolium pratense L.), chasteberry (Vitex agnus-castus L.), and
hops (Humulus lupulus L.) showed significant competitive binding to estrogen
receptors alpha (ER alpha) and beta (ER beta). With cultured Ishikawa
(endometrial) cells, red clover and hops exhibited estrogenic activity as
indicated by induction of alkaline phosphatase (AP) activity and up-regulation
of progesterone receptor (PR) mRNA. Chasteberry also stimulated PR expression,
but no induction of AP activity was observed. In S30 breast cancer cells, pS2
(presenelin-2), another estrogen-inducible gene, was up-regulated in the
presence of red clover, hops, and chasteberry. Interestingly, extracts of Asian
ginseng (Panax ginseng C.A. Meyer) and North American ginseng (Panax
quinquefolius L.) induced pS2 mRNA expression in S30 cells, but no significant
ER binding affinity, AP induction, or PR expression was noted in Ishikawa cells.
Dong quai [Angelica sinensis (Oliv.) Diels] and licorice (Glycyrrhiza glabra L.)
showed only weak ER binding and PR and pS2 mRNA induction. Black cohosh
[Cimicifuga racemosa (L.) Nutt.] showed no activity in any of the above in vitro
assays. Bioassay-guided isolation utilizing ER competitive binding as a monitor
and screening using ultrafiltration LC-MS revealed that genistein was the most
active component of red clover. Consistent with this observation, genistein was
found to be the most effective of four red clover isoflavones tested in the
above in vitro assays. Therefore, estrogenic components of plant extracts can be
identified using assays for estrogenic activity along with screening and
identification of the active components using ultrafiltration LC-MS. These data
suggest a potential use for some dietary supplements, ingested by human beings,
in the treatment of menopausal symptoms.

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

PMID: 11368622 [PubMed - indexed for MEDLINE]

80: Boll Chim Farm. 2000 Sep-Oct;139(5):225-7.

In vitro anti-mycotic activity of some medicinal plants containing flavonoids.

Trovato A, Monforte MT, Forestieri AM, Pizzimenti F.

Pharmaco-Biological Department, School of Pharmacy, Vill. SS. Annunziata, 98168
Messina.

Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck),
Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa
canina L. and Ruta graveolens L. have been studied. The antimycotic activity was
evaluated "in vitro" on strains of Candida albicans isolated from clinical
samples obtained in the course of acute vaginitis.

PMID: 11213443 [PubMed - indexed for MEDLINE]

81: Phytochemistry. 2000 Nov;55(5):447-56.

Flavonoid constituents from Glycyrrhiza glabra hairy root cultures.

Li W, Asada Y, Yoshikawa T.

School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.

An unusual biflavonoid named licoagrodin was isolated from the hairy root
cultures of Glycyrrhiza glabra (Leguminosae) along with three prenylated
retrochalcones, licoagrochalcones B, C, D, a prenylated aurone, licoagroaurone
and four known prenylated flavonoids, licochalcone C, kanzonol Y, glyinflanin B
and glycyrdione A. From the glycosidic fraction, a isoflavone glycoside,
licoagroside A, and a maltol glycoside, licoagroside B were isolated together
with four known isoflavone glycosides, two flavone C-glycosides, and three other
glycosides. Their structures were elucidated on the basis of spectroscopic
evidence.

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

PMID: 11140606 [PubMed - indexed for MEDLINE]

82: Bull Exp Biol Med. 2000 Jul;130(7):658-60.

Antioxidant activity of parapharmaceutics containing natural inhibitors of free
radical processes.

Konovalova GG, Tikhaze AK, Lankin VZ.

Laboratory of Biochemistry of Free Radical Processes, AL Myasnikov Institute of
Cardiology, Russian Cardiology Research-and-Production Center, Russian Ministry
of Health, Moscow.

The duration of lag phase of ascorbate-dependent free radical oxidation of
endogenous polyenic lipids in rat liver and myocardium considerably increased
after oral administration of lacrinat containing licorice Glycyrrhiza glabra
root powder for 1 month. Lacrinat markedly decreased the content of lipid
peroxides in rat liver. Ex vivo antioxidant effects of lacrinat in rat liver
were comparable with those of beta-carotene-containing preparations carinat and
carinat CD. Parapharmaceutics containing both licorice Glycyrrhiza glabra root
powder and beta-carotene (carinat forte) markedly increased antioxidant activity
of the liver.

PMID: 11140579 [PubMed - indexed for MEDLINE]

83: Phytochemistry. 2000 Oct;55(4):323-6.

Biosynthesis of the dimethylallyl moiety of glabrol in Glycyrrhiza glabra hairy
root cultures via a non-mevalonate pathway.

Asada Y, Li W, Yoshikawa T.

School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
[email protected]

Incorporation of [1-13C]glucose indicates that the biosynthesis of the
hemiterpene moiety of glabrol, the main prenylated flavanone in the hairy root
cultures of Glycyrrhiza glabra, proceeds via a glyceraldehyde/pyruvate
non-mevalonate pathway.

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

PMID: 11117880 [PubMed - indexed for MEDLINE]

84: Eksp Klin Farmakol. 2000 Sep-Oct;63(5):59-61.

[Medicinal plant preparations used as adjuvant therapeutics in experimental
oncology]

[Article in Russian]

Razina TG, Zueva EP, Amosova EN, Krylova SG.

Tomsk Scientific Center, Siberian Division, Russian Academy of Medical Sciences,
Russia.

Experiments on mice inoculated with metastasing Lewis lung carcinoma showed that
the antitumor and antimetastatic effects of cyclophosphan (cyclophosphamide) are
potentiated by the extracts of phytopreparations based on Baikal scullcap
(Scutellaria baikalensis), rhodiola (Rhodiola rosea), common licorice
(Glycyrrhiza glabra), and their principal acting components--baikalin,
paratyrosol, and glycyrram.

Publication Types:
English Abstract

PMID: 11109531 [PubMed - indexed for MEDLINE]

85: Planta Med. 2000 Oct;66(7):607-11.

Pharmacological effects of urinary products obtained after treatment with
saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic
reaction.

Taniguchi C, Homma M, Takano O, Hirano T, Oka K, Aoyagi Y, Niitsuma T, Hayashi
T.

Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life
Science, Japan.

To define the anti-allergic components in Saiboku-To, a herbal medicine for
bronchial asthma, we examined the effects of 11 compounds found in
post-administrative urine of Saiboku-To on concanavalin A-induced human
lymphocyte blastogenesis in vitro and picryl chloride (PC)-induced mouse ear
swelling in vivo. The urinary products of Saiboku-To were flavonoids and lignans
derived from the constitutional herbs and their hydrogenated metabolites.
Medicarpin derived from Glycyrrhiza glabra, magnolol and
8,9-dihydroxydihydromagnolol from Magnolia officinalis, baicalein, wogonin and
oroxylin A from Suctellaria baicalensis inhibited lymphocyte blastogenesis in
dose-dependent fashion with IC50 values ranging from 3.0 to 7.7 micrograms/mL,
which corresponded to 20-100 times that of prednisolone IC50 (0.08
microgram/mL). Davidigenin, dihydrowogonin and dihydrooroxylin A, which are
hydrogenated metabolites of liquiritigenin, wogonin and oroxylin A,
respectively, had no or little effects on lymphocyte blastogenesis. Oral
administration of Saiboku-To, medicarpin, baicalein, magnolol and baicalin (100
mg/kg), inhibited PC-induced ear swelling significantly by 23.5, 40.1, 30.5,
23.6 and 20.9%, respectively, though the effects were weaker than that of 5
mg/kg of prednisolone (52.9%). The results suggested that flavonoids and lignans
tested in the present study were implicated in anti-asthmatic effect of
Saiboku-To through suppression of type IV allergic reaction.

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

PMID: 11105563 [PubMed - indexed for MEDLINE]

86: Biosci Biotechnol Biochem. 2000 Sep;64(9):1967-9.

Tyrosinase inhibitory activity of Bangladeshi indigenous medicinal plants.

Khanom F, Kayahara H, Tadasa K.

The United Graduate School of Agricultural Science, Gifu University, Japan.

The tyrosinase-inhibitory activity of 15 kinds of Bangladeshi medicinal plants
was evaluated. Methanol extracts were prepared for screening tests, and other
kinds of extracts were also studied for those with high activity. Swertia
chirata, Piper nigrum, Glycyrrhiza glabra, Piper longam and Ocimum americanum
were screened as highly inhibiting samples. Methanol was found to be the most
efficient solvent for extracting the active compounds. The 50%
tyrosinase-inhibitory concentration of the Glycyrrhiza glabra methanol extract
was 21.2 microg/ml.

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

PMID: 11055404 [PubMed - indexed for MEDLINE]

87: Phytomedicine. 2000 Jul;7(4):273-82.

An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected
commercial herbal extracts and tinctures.

Budzinski JW, Foster BC, Vandenhoek S, Arnason JT.

Ottawa-Carleton Institute of Biology, University of Ottawa, Ontario, Canada.

Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and
13 related pure plant compounds have been analyzed for their in vitro cytochrome
P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate
assay. Roughly 75% of the commercial products and 50% of the pure compounds
showed significant inhibition of CYP3A4 metabolite formation. For each herbal
product and pure compound exhibiting dose-dependency, the inhibition values were
used to generate median inhibitory concentration (IC50) curves using linear
regression. Among the commercial extracts, Hydrastis canadensis (goldenseal),
Hypericum perforatum (St. John's wort), and Uncaria tomentosa (cat's claw) had
the lowest IC50 values at < 1% full strength, followed by Echinacea angustifolia
roots, Trifolium pratense (wild cherry), Matricaria chamomilla (chamomile), and
Glycyrrhiza glabra (licorice), which had IC50 values ranging from 1%-2% of full
strength. Dillapiol, hypericin, and naringenin had the lowest IC50 values among
the pure plant compounds at < 0.5 mM; dillapiol was the most potent inhibitor at
23.3 times the concentration of the positive CYP3A4 inhibitor ketoconazole.
Utilizing high-throughput screening methodologies for assessing CYP3A4
inhibition by natural products has important implications for predicting the
likelihood of potential herbal-drug interactions, as well as determining
candidates for further in-depth analyses.

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

PMID: 10969720 [PubMed - indexed for MEDLINE]

88: Ceska Slov Farm. 2000 Jul;49(4):162-7.

[Interactions between herbal medicines and drugs]

[Article in Czech]

Tumova L.

Katedra farmakognozie Farmaceuticke fakulty Univerzity Karlovy, Hradec Kralove.

At present the use of medicaments of plant origin is on the increase. It is
therefore necessary to take into consideration that there exist known as well as
potential interactions between the medicament of the medicinal plant. The
problematic plants include Echinacea, Allium cepa, Gingko biloba, Panax ginseng,
as well as Hypericum perforatum, Valeriana officinalis, or Glycyrrhiza glabra.
Its use should be limited, or completely excluded in the cases of simultaneous
therapy with, e.g., warfarin, hepatotoxically acting medicaments, MAOI
inhibitors, phenelzin sulphate, or phenytoin, as they may decrease of completely
eliminate the therapeutic effect of the administered drugs, or they may cause a
toxic damage to the organism.

Publication Types:
English Abstract

PMID: 10953464 [PubMed - indexed for MEDLINE]

89: Biol Pharm Bull. 2000 May;23(5):602-6.

Phylogenetic relationship of six Glycyrrhiza species based on rbcL sequences and
chemical constituents.

Hayashi H, Hosono N, Kondo M, Hiraoka N, Ikeshiro Y, Shibano M, Kusano G,
Yamamoto H, Tanaka T, Inoue K.

Gifu Pharmaceutical University, Japan. [email protected]

The nucleotide sequences of ribulose-1,5-bisphosphate carboxylase/oxygenase
large subunit gene (rbcL) of Glycyrrhiza glabra, G. uralensis, G. inflata, G.
echinata, G. macedonica and G. pallidiflora have been determined to construct
their phylogenetic tree. Based on these sequences, the six Glycyrrhiza species
were divided into two groups: three, G. glabra, G. uralensis, and G. inflata,
which produce glycyrrhizin as a major saponin, and the others, G. echinata, G.
macedonica and G. pallidiflora, which produce macedonoside C as a major saponin.
Among the three glycyrrhizin-producing species, only two nucleotide
substitutions were observed between the rbcL sequences of G. glabra and G.
uralensis, and the sequence of G. uralensis was identical to that of G. inflata,
indicating that G. uralensis and G. inflata are closely related. Among the three
macedonoside C-producing species, only one nucleotide substitution was observed
between those of G. echinata and G. macedonica, indicating that these two
species are also closely related.

Publication Types:
Comparative Study

PMID: 10823673 [PubMed - indexed for MEDLINE]

90: J Pharm Pharmacol. 2000 Feb;52(2):219-23.

Protection of mitochondrial functions against oxidative stresses by isoflavans
from Glycyrrhiza glabra.

Haraguchi H, Yoshida N, Ishikawa H, Tamura Y, Mizutani K, Kinoshita T.

Faculty of Engineering, Fukuyama University, Japan.

Isoflavan derivatives, glabridin (1), hispaglabridin A (2), hispaglabridin B
(3), 4'-Omethylglabridin (4) and 3'-hydroxy-4'-O-methylglabridin (5), isolated
from Glycyrrhiza glabra, were investigated for their ability to protect liver
mitochondria against oxidative stresses. Mitochondrial lipid peroxidation linked
to respiratory electron transport and that induced non-enzymatically were
inhibited by these isoflavans. Hispaglabridin A (2) strongly inhibited both
peroxidations and 3'-hydroxy-4'-O-methylglabridin (5) was the most effective at
preventing NADH-dependent peroxidation. 3'-Hydroxy-4'-O-methylglabridin (5)
protected mitochondrial respiratory enzyme activities against NADPH-dependent
peroxidation injury. Dihydroxyfumarate-induced mitochondrial peroxidation was
also prevented by this isoflavan. Isoflavans from G. glabra were shown to be
effective in protecting mitochondrial function against oxidative stresses.

PMID: 10714953 [PubMed - indexed for MEDLINE]

91: Biol Pharm Bull. 2000 Feb;23(2):231-4.

Molecular cloning and characterization of a cDNA for Glycyrrhiza glabra
cycloartenol synthase.

Hayashi H, Hiraoka N, Ikeshiro Y, Kushiro T, Morita M, Shibuya M, Ebizuka Y.

Niigata College of Pharmacy, Japan.

A cDNA clone (GgCAS1) encoding cycloartenol synthase (CAS) has been isolated
from Glycyrrhiza glabra (licorice) by cross-hybridization with that of Pisum
sativum CAS as a probe. The deduced amino acid sequence of GgCAS1 exhibits 89%,
83% and 81% identity to those of Pisum sativum, Panax ginseng and Arabidopsis
thaliana CASs, respectively. CAS activity has been detected in the homogenate of
the yeast transformed with the expression vector containing the open reading
frame of GgCAS1. Southern blot analysis suggested that at least two CAS genes
exist in the licorice genome. In Northern blot analysis, the strong signal for
CAS mRNA is detected in the cultured licorice cells of all growth phases, but no
significant increase of CAS mRNA expression was observed in the cells treated
with the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor, pravastatin.

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

PMID: 10706391 [PubMed - indexed for MEDLINE]

92: Lancet. 2000 Jan 8;355(9198):134-8.

Erratum in:
Lancet 2000 Mar 18;355(9208):1020.

Comment in:
Lancet. 2000 Mar 18;355(9208):1019-20.

Herb-drug interactions.

Fugh-Berman A.

George Washington University School of Medicine and Health Sciences, Department
of Health Care Sciences, Washington, DC 20037, USA. [email protected]

Concurrent use of herbs may mimic, magnify, or oppose the effect of drugs.
Plausible cases of herb-drug interactions include: bleeding when warfarin is
combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai
(Angelica sinensis), or danshen (Salvia miltiorrhiza); mild serotonin syndrome
in patients who mix St John's wort (Hypericum perforatum) with
serotonin-reuptake inhibitors; decreased bioavailability of digoxin,
theophylline, cyclosporin, and phenprocoumon when these drugs are combined with
St John's wort; induction of mania in depressed patients who mix antidepressants
and Panax ginseng; exacerbation of extrapyramidal effects with neuroleptic drugs
and betel nut (Areca catechu); increased risk of hypertension when tricyclic
antidepressants are combined with yohimbine (Pausinystalia yohimbe);
potentiation of oral and topical corticosteroids by liquorice (Glycyrrhiza
glabra); decreased blood concentrations of prednisolone when taken with the
Chinese herbal product xaio chai hu tang (sho-salko-to); and decreased
concentrations of phenytoin when combined with the Ayurvedic syrup
shankhapushpi. Anthranoid-containing plants (including senna [Cassia senna] and
cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and
psyllium) can decrease the absorption of drugs. Many reports of herb-drug
interactions are sketchy and lack laboratory analysis of suspect preparations.
Health-care practitioners should caution patients against mixing herbs and
pharmaceutical drugs.

Publication Types:
Review

PMID: 10675182 [PubMed - indexed for MEDLINE]

93: Biol Pharm Bull. 1999 Sep;22(9):947-50.

Molecular cloning and characterization of two cDNAs for Glycyrrhiza glabra
squalene synthase.

Hayashi H, Hirota A, Hiraoka N, Ikeshiro Y.

Niigata College of Pharmacy, Japan.

Two cDNAs (GgSQS1 and GgSQS2) encoding squalene synthase have been isolated from
licorice, Glycyrrhiza glabra L., and characterized. The deduced amino acid
sequence of GgSQS1 was 88%, 81%, 78%, 45-44%, and 45-41% identical to those of
GgSQS2, Nicotiana, Arabidopsis, mammal and yeast squalene synthases,
respectively. Squalene synthase activity was found in the cell-free extracts of
Escherichia coli transformed with the recombinant plasmids for GgSQS1 and
GgSQS2, respectively. Genomic Southern blot hybridization indicated that there
are three squalene synthase genes in the licorice genome. Northern blot analysis
showed that GgSQS2 mRNA is mainly expressed during the exponential growth phase
of the cultured licorice cells.

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

PMID: 10513618 [PubMed - indexed for MEDLINE]

94: Altern Med Rev. 1999 Jun;4(3):178-88.

A review of plants used in the treatment of liver disease: part two.

Luper S.

Southwest College of Naturopathic Medicine: 2140 East Broadway Rd. Tempe, AZ
85282, USA. [email protected]

Botanical medicines have been used traditionally by herbalists and indigenous
healers worldwide for the prevention and treatment of liver disease. Clinical
research in this century has confirmed the efficacy of several plants in the
treatment of liver disease, while basic scientific research has uncovered the
mechanisms by which some plants provide their therapeutic effects. This article
is Part Two in a review of botanicals used in the treatment of liver disease.
Curcuma longa (turmeric), Camellia sinensis (green tea), and Glycyrrhiza glabra
(licorice) are reviewed in this installment. Silybum marianum (milk thistle) and
Picrorhiza kurroa (kutkin) were reviewed in Part One.

Publication Types:
Review

PMID: 10383482 [PubMed - indexed for MEDLINE]

95: Planta Med. 1998 Dec;64(8):746-7.

Antimicrobial flavonoids from Glycyrrhiza glabra hairy root cultures.

Li W, Asada Y, Yoshikawa T.

A new compound named licoagrodione was isolated from the hairy root cultures of
Glycyrrhiza glabra (Fabaceae) together with five known prenylated flavonoids.
The structure of licoagrodione has been elucidated on the basis of spectral
evidence and it was found to have antimicrobial activity indicated by disc
diffusion method.

Publication Types:
Letter

PMID: 9933991 [PubMed - indexed for MEDLINE]

96: Biol Pharm Bull. 1998 Oct;21(10):1110-2.

Activation of macrophages by crude polysaccharide fractions obtained from shoots
of Glycyrrhiza glabra and hairy roots of Glycyrrhiza uralensis in vitro.

Nose M, Terawaki K, Oguri K, Ogihara Y, Yoshimatsu K, Shimomura K.

Department of Pharmacognosy and Plant Chemistry, Faculty of Pharmaceutical
Sciences, Nagoya City University, Nagoya, Japan.

Many plant polysaccharide fractions have been reported as immunomodulatory
agents. However, sometimes the possibility of contamination with bacterial
lipopolysaccharide (LPS), a potent B cell mitogen and immune modulator, is
discussed. In the present paper, we investigated the effects of crude
polysaccharide fractions obtained from the shoot and hairy root of Glycyrrhizae
sp. on murine peritoneal macrophage function, in order to clarify whether plants
grown under aseptic conditions produce immunomodulatory polysaccharides. All
crude polysaccharide fractions induced nitric oxide production by murine
peritoneal macrophages in vitro. Chemical analysis revealed that LPS-like
molecules were not present in all preparations. These results suggested that
shoot and hairy root biosynthesized polysaccharides that could stimulate
macrophages de novo.

PMID: 9821821 [PubMed - indexed for MEDLINE]

97: Acta Pharm Hung. 1998 Sep;68(5):263-8.

[Polysaccharides of Glycyrrhiza glabra L. and Glycyrrhiza echinata L. Medicinal
plants II]

[Article in Hungarian]

Kiss T, Gyemant G, Danos B, Nanasi P.

Kossuth Lajos Tudomanyegyetem Biokemiai Tanszek, Debrecen, Hungary.

Comparative study was carried out among the polysaccharides of Chinese,
Lithuanian and Hungarian origin Glycyrrhiza glabra root samples as well as the
Hungarian origin Glycyrrhiza echinata, which has not been studied earlier. The
plant material was extracted with boiling water and the yield, the carbohydrate
and the uronic acid content was measured by the alpha-naphtol and the Bitter
method [21], respectively. Although the yield of Hungarian origin species was
found lower than the yield of eastern species, the uronic acid content was
similar. (Table I.) Our results show that to extract polysaccharides containing
uronic acids needed longer extraction time, about 4 hours. The stem of
Glycyrrhiza echinata might be useful from a practical point of view because of
its large size and easy of access. (Table I. II.) Some fractions containing
uronic acid in higher amount were separated on DEAE Sepharose CL-6B anion
exchange column. After hydrolysis, reduction and acetylation the monosaccharide
composition of this fractions was analysed by GC. (Table IV.).

Publication Types:
English Abstract

PMID: 9805811 [PubMed - indexed for MEDLINE]

98: Biol Pharm Bull. 1998 Sep;21(9):987-9.

Seasonal variation of glycyrrhizin and isoliquiritigenin glycosides in the root
of Glycyrrhiza glabra L.

Hayashi H, Hiraoka N, Ikeshiro Y, Yamamoto H, Yoshikawa T.

Niigata College of Pharmacy, Japan.

The time courses of the glycyrrhizin and isoliquiritigenin glycoside contents in
the thickening roots of licorice, Glycyrrhiza glabra L., have been determined.
The glycyrrhizin content in 1-year-old roots rapidly increased from October to
November, whereas the isoliquiritigenin glycoside content increased up to
October. In 3-year-old plants, although the isoliquiritigenin glycoside content
rapidly increased from June to July, the glycyrrhizin content did not show any
significant increase from May to August. The glycyrrhizin content increased
during the senescence of the aerial parts as well as during the early stage of
shoot elongation. The incorporation of [14C]mevalonic acid into the glycyrrhizin
fraction by the root segments was high in May, June and September, and low in
August and winter. These results indicated that the biosynthesis of glycyrrhizin
is differently regulated from that of isoliquiritigenin glycoside in the
thickening root of G. glabra.

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

PMID: 9781853 [PubMed - indexed for MEDLINE]

99: Biol Pharm Bull. 1998 Jul;21(7):782-3.

Phylogenetic relationship of Glycyrrhiza plants based on rbcL sequences.

Hayashi H, Hosono N, Kondo M, Hiraoka N, Ikeshiro Y.

Niigata College of Pharmacy, Japan.

The nucleotide sequences of the ribulose-1,5-bisphosphate carboxylase/oxygenase
large subunit gene (rbcL) of Glycyrrhiza glabra, G. uralensis, G. inflata, G.
echinata, and G. pallidiflora have been determined to construct the phylogenetic
tree. In the phylogenetic tree based on the rbcL sequences, the five Glycyrrhiza
species were divided into two groups: the three glycyrrhizin-producing species
G. glabra, G. uralensis, and G. inflata; and the two glycyrrhizin-nonproducing
species G. echinata and G. pallidiflora. Among the three glycyrrhizin-producing
species, only two nucleotide substitutions were observed between the rbcL
sequence of G. glabra and G. uralensis, and the sequence of G. uralensis was
identical to that of G. inflata, indicating that the three
glycyrrhizin-producing species are closely related.

PMID: 9703269 [PubMed - indexed for MEDLINE]

100: Free Radic Biol Med. 1998 Jun;24(9):1419-29.

Structural aspects of the inhibitory effect of glabridin on LDL oxidation.

Belinky PA, Aviram M, Mahmood S, Vaya J.

Laboratory of Natural Compounds for Medical Use, Migal, Galilee Technological
Center, Kiryat Shmona, Israel.

The inhibitory effects of glabridin, an isoflavan isolated from licorice
(Glycyrrhiza glabra) root, and its derivatives on the oxidation of LDL induced
by copper ions or mediated by macrophages were studied, in order to evaluate the
contribution of the different parts of the isoflavan molecule to its antioxidant
activity. The peak potential (E1/2) of the isoflavan derivatives, their radical
scavenging capacity toward 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical and
their ability to chelate heavy metals were also analyzed and compared to their
inhibitory activity on LDL oxidation. In copper ion-induced LDL oxidation,
glabridin (1), 4'-O-methylglabridin (2), hispaglabridin A (3), and
hispaglabridin B (4), which have two hydroxyl groups at positions 2' and 4' or
one hydroxyl at position 2' on ring B, successfully inhibited the formation of
conjugated dienes, thiobarbituric acid reactive substances (TBARS) and lipid
peroxides, and inhibited the electrophoretic mobility of LDL under oxidation.
Compounds 1-3 exhibited similar activities, whereas compound 4 was less active.
In macrophage-mediated LDL oxidation, the TBARS formation was also inhibited by
these isoflavans (1-4) at a similar order of activity to that obtained in copper
ion-induced LDL oxidation. On the other hand, 2'-O-methylglabridin (5), a
synthesized compound, whose hydroxyl at 2'-position is protected and the
hydroxyl at 4'-position is free, showed only minor inhibitory activity in both
LDL oxidation systems. 2',4'-O-Dimethylglabridin (6), whose hydroxyls at 2'- and
4'-positions are both protected, was inactive. Resorcinol (7), which is
identical to the phenolic B ring in glabridin, presented low activity in these
oxidation systems. The isoflavene glabrene (8), which contains an additional
double bond in the heterocyclic C ring, was the most active compound of the
flavonoid derivatives tested in both oxidation systems. The peak potential of
compounds 1-5 (300 microM), tested at pH 7.4, was similar (425-530 mV), and that
for compound 6 and 8 was 1078 and 80 mV, respectively. Within 30 min of
incubation, compounds 1, 2, 3, 4, 8 scavenged 31%, 16%, 74%, 51%, 86%,
respectively, of DPPH radical, whereas compounds 5 and 6, which almost did not
inhibit LDL oxidation, also failed to scavenge DPPH. None of the isoflavan
derivatives nor the isoflavene compound were able to chelate iron, or copper
ions. These results suggest that the antioxidant effect of glabridin on LDL
oxidation appears to reside mainly in the 2' hydroxyl, and that the hydrophobic
moiety of the isoflavan is essential to obtain this effect. It was also shown
that the position of the hydroxyl group at B ring significantly affected the
inhibitory efficiency of the isoflavan derivatives on LDL oxidation, but did not
influence their ability to donate an electron to DPPH or their peak potential
values.

PMID: 9641259 [PubMed - indexed for MEDLINE]

101: Atherosclerosis. 1998 Mar;137(1):49-61.

The antioxidative effects of the isoflavan glabridin on endogenous constituents
of LDL during its oxidation.

Belinky PA, Aviram M, Fuhrman B, Rosenblat M, Vaya J.

Laboratory of Natural Compounds for Medical Use, Migal, Galilee Technological
Center, Kiryat Shmona, Israel.

The effect of the consumption of glabridin, an isoflavan isolated from
Glycyrrhiza glabra (licorice) root, on the susceptibility of low density
lipoprotein (LDL) to oxidation was studied in atherosclerotic apolipoprotein E
deficient (E[o] mice) and was compared with that of the known flavonoids,
quercetin and catechin. Glabridin inhibitory activity on in vitro oxidation of
human LDL was also investigated by determining the formation of lipid peroxides
and oxysterols and the consumption of LDL-associated lipophilic antioxidants.
Determination of the extent of LDL oxidation by measuring the formation of
thiobabituric acid reactive substances (TBARS) after 2 h of LDL incubation with
CuSO4 (10 microM) or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) (5
mM), revealed that glabridin or quercetin consumption resulted in a 53 and 54%
reduction in copper ion induced oxidation, respectively, and a 95 and 83%
reduction in AAPH induced LDL oxidation, respectively. No inhibition was
obtained with consumption of catechin. About 80% of glabridin was found to bind
to the LDL human particle. In the in vitro oxidation of LDL induced by AAPH (5
mM), glabridin inhibited the formation of TBARS, lipid peroxides and cholesteryl
linoleate hydroperoxide (CLOOH) at all the concentrations tested (5-60 microM),
while in oxidation induced by copper ions (10 microM), glabridin exhibited a
pro-oxidant activity at concentrations lower than 20 microM, and a clear
antioxidant activity at concentrations greater than 20 microM. Glabridin (30
microM) inhibited the formation of cholest-5-ene-3,7-diol
(7-hydroxycholesterol), cholest-5-ene-3-ol-7-one (7-ketocholesterol) and
cholestan-5,6-epoxy-3-ol (5,6-epoxycholesterol) after 6 h of AAPH induced LDL
oxidation, by 55, 80 and 40%, respectively, and after 6 h of copper ion induced
LDL oxidation, by 73, 94 and 52%, respectively. Glabridin also inhibited the
consumption of beta-carotene and lycopene by 38 and 52%, respectively, after 0.5
h of LDL oxidation with AAPH, but failed to protect vitamin E. The in vivo and
in vitro reduction of the susceptibility of LDL to oxidation obtained with
glabridin, may be related to the absorption or binding of glabridin to the LDL
particle and subsequent protection of LDL from oxidation by inhibiting the
formation of lipid peroxides and oxysterols, and by protecting LDL associated
carotenoids.

PMID: 9568736 [PubMed - indexed for MEDLINE]

102: Arch Biochem Biophys. 1998 Jan 15;349(2):205-15.

Molecular characterization of tobacco squalene synthase and regulation in
response to fungal elicitor.

Devarenne TP, Shin DH, Back K, Yin S, Chappell J.

Agronomy Department, University of Kentucky, Lexington 40546-0091, USA.

The enzyme squalene synthase (SS) represents the first commitment of carbon from
the general isoprenoid pathway toward sterol biosynthesis and is a potential
point for regulation of sterol biosynthesis. The isolation and characterization
of tobacco (Nicotiana tabacum) squalene synthase (TSS) cDNA and genomic DNA
clones, as well as determination of the steady state level of TSS mRNA in
response to elicitor treatment, were investigated. cDNA clones for TSS were
isolated from poly (A)+ RNA using a reverse transcription/polymerase chain
reaction (RT/PCR) method. A 1233-bp cDNA clone was generated that contained an
open reading frame of 411 amino acids giving a predicted molecular mass of 46.9
kDa. Comparison of the TSS deduced amino acid sequence with currently described
SS from different species showed the highest identify with Nicotiana benthamiana
(97%), followed by Glycyrrhiza glabra (81%), Arabidopsis thaliana (74%), rat
(40%), and yeast (37%). Expression of a soluble form of the TSS enzyme with
enzymatic activity in Escherichia coli was achieved by truncating 24 hydrophobic
amino acids at the carboxy terminus. Characterization of genomic TSS (gTSS)
revealed a gene of 7.086 kb with a complex organization of small exons and large
introns not typical of plant genes. Southern blot hybridization indicated only
two copies of the SS gene in the tobacco genome. Treatment of tobacco cell
suspension cultures with a fungal elicitor dramatically reduced TSS enzymatic
activity, lowering it to zero within 24 h. Analysis of TSS mRNA levels, by RNA
blot hybridization and primer extension assays, in elicitor-treated cells
indicated that the transcript level remained largely unchanged over this 24-h
period. These results suggest that the suppression of TSS enzyme activity in
elicitor-treated cells may result from a posttranscriptional modification of
TSS.

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

PMID: 9448707 [PubMed - indexed for MEDLINE]

103: Biochem Biophys Res Commun. 1997 Jun 9;235(1):259-63.

Erratum in:
Biochem Biophys Res Commun 1997 Aug 8;237(1):203. Francischetti B [corrected
to Francischetti IM].

Identification of glycyrrhizin as a thrombin inhibitor.

Francischetti IM, Monteiro RQ, Guimaraes JA.

Department of Medical Biochemistry, ICB/CCS, Federal University of Rio de
Janeiro, Brazil.

Glycyrrhizin (GL), an anti-inflammatory compound isolated from Glycyrrhiza
glabra, was identified as a new thrombin inhibitor: (a) It prolonged plasma
recalcification and thrombin and fibrinogen clotting times, and (b) it inhibited
thrombin-induced, but not collagen-, PAF- or convulxin-induced platelet
aggregation. On the other hand, GL did not block thrombin's amidolytic activity
upon S-2238. Furthermore, the fluorescence emission intensity of dansyl-thrombin
was increased upon GL binding. Moreover, GL displaced hirudin as an inhibitor of
thrombin-catalyzed hydrolysis of S-2238. Our data provide evidence that GL is a
selective inhibitor of thrombin (the first one isolated from plants) that is
able to exert its anti-thrombin action by interacting with the enzyme's anion
binding exosite 1. A pharmacophoric search identified GL as a sialyl Lewis X
(SLe[X]) mimetic compound able to inhibit selectin binding to SLe(X). However,
SLe(X) did not affect thrombin clotting activities, which indicates a lack of
its interaction with thrombin and distinguishes both molecules. It is suggested
that the anti-inflammatory effect of GL may be due to its effective
anti-thrombin action.

PMID: 9196073 [PubMed - indexed for MEDLINE]

104: J Commun Dis. 1997 Jun;29(2):91-9.

In vitro antiviral activity of indigenous glycyrrhizin, licorice and
glycyrrhizic acid (Sigma) on Japanese encephalitis virus.

Badam L.

National Institute of Virology, Pune, India.

Glycyrrhizin, a triterpenoid glycoside and Licorice from Glycyrrhiza glabra and
Ammonium salt of Glycyrrhizic acid (Sigma) were tested for antiviral activity on
three strains of Japanese encephalitis virus (JEV), Nakayama, P-20778 and 821564
XY48. Purified glycyrrhizin (M.w. 822.92) inhibited plaque formation in all the
three strains of JEV at a concentration of 500 micrograms/ml at 96 hrs, Similar
effect was observed at 1000 micrograms/ml concentration with Licorice and
Ammonium salt of glycyrrhizic acid. The minimal inhibitory concentrations were
not toxic to porcine stable kidney (PS) and human cervical carcinoma (HeLa) cell
lines. Cyctotoxicity of these chemicals was evaluated by trypan blue dye
exclusion test which indicated subtoxic concentrations at 5,000 micrograms/ml at
96 hrs and toxic concentrations were 10,000 micrograms/ml at the same time
period for the host cells PS. Thus the indigenously purified glycyrrhizin seems
to be more potent antiviral agent than Licorice and ammonium salt of
glycyrrhizic acid (Sigma) for JEV 'in vitro'.

PMID: 9282507 [PubMed - indexed for MEDLINE]

105: Biomed Chromatogr. 1997 May-Jun;11(3):125-31.

Systematic analysis of post-administrative saiboku-to urine by liquid
chromatography to determine pharmacokinetics of traditional Chinese medicine.

Homma M, Oka K, Taniguchi C, Niitsuma T, Hayashi T.

Department of Clinical Pharmacology, Tokyo University of Pharmacy & Life
Science, Japan.

To disclose the mystery of a traditional Chinese medicine and to identify
biologically active components, we analysed post-administrative urine for
Saiboku-To, an anti-asthmatic Chinese herbal remedy. Systematic analysis of the
components appearing in the urine was carried out by high-performance liquid
chromatography (HPLC) with normal- and reversed-phase modes in combination.
beta-D-glucuronidase-treated urine was subjected to rapid-flow fractionation
(RFF) to achieve fractional extraction of lipophilic components with exhaustive
recovery rates. The extracts were analysed by HPLC equipped with a multi-channel
UV-detector. In the first stage of HPLC, we conducted a normal-phase mode run to
find magnolol derived from Magnolia officinalis, as the most hydrophobic
component showing minimum retention time among the urinary products of
Saiboku-To. In the next stage, mobile phase solvent composition for
reversed-phase HPLC was optimized so as to retain magnolol up to 60 min. Under
these conditions, other Saiboku-To urinary products, which were more polar than
magnolol, appeared within 60 min. Our HPLC method used marker compounds like
magnolol and could indicate the terminal peak position on the reversed-phase
chromatography. We found a total of eight components in the post-administrative
Saiboku-To urine. Structure identification of the isolated pure materials was
achieved using nuclear magnetic resonance (NMR)-, mass (MS)- and UV-spectra, and
HPLC retention profiles. They were magnolol and 8,9-dihydroxydihydromagnolol
stemming from M. officinalis, medicarpin and liquiritigenin from Glycyrrhiza
glabra, baicalein, wogonin, and oroxylin A from Scutellaria baicalensis, and
davidigenin of an unknown origin. The pharmacological mystery of Saiboku-To
should be disclosed by resolving the pharmacokinetics and pharmacodynamics of
these urinary products independently and synergistically.

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

PMID: 9192103 [PubMed - indexed for MEDLINE]

106: Planta Med. 1997 Apr;63(2):115-9.

Effect of Glycyrrhiza glabra roots and glycyrrhizin on the glucuronidation in
rats.

Moon A, Kim SH.

College of Pharmacy, Duksung Women's University, Seoul, Korea.

As an approach to elucidate the possible in vivo interaction of synthetic drugs
and herbs which are frequently used in combination in Asia, the effect of
Glycyrrhiza glabra on the metabolism of acetaminophen (AAP) was examined in male
Sprague-Dawley rats. The pretreatment of the methanol extract of Glycyrrhiza
glabra roots (Glycyrrhizae Radix, GR, 1 g/kg, p.o.) for 6 days significantly
increased the cumulative biliary (156%) and urinary (132%) excretions of
AAP-glucuronide conjugate within 120 min after the administration of AAP (150
mg/kg, i.v.) without affecting thioether and sulfate conjugates. These findings
suggest that GR might enhance the glucuronidation pathway of AAP. In order to
study the effect of GR on the glucuronidation in rat liver, we examined
enzymatic activity of p-nitrophenol UDP-glucuronosyltransferase (UGT), which is
also called UGT1A, and intracellular concentrations of hepatic UDP-glucuronic
acid, upon the administration of GR (1 g/kg, p.o.) or glycyrrhizin (23 mg/kg,
p.o.), a major component of GR, for 6 days. GR and glycyrrhizin caused increases
in specific activities of UGT1A by 111% and 96%, respectively. Concentration of
UDP-glucuronic acid was increased 257% by GR and 484% by glycyrrhizin. These
data indicate that GR and glycyrrhizin activated glucuronidation and thus
suggest the possibility that GR may influence detoxification of xenobiotics in
rat liver. Using the p-nitrophenol UGT1A1 cDNA as a probe, we found that the
activation of UGT1A by GR was not due to the induction of mRNAs for the enzyme.

PMID: 9140223 [PubMed - indexed for MEDLINE]

107: Free Radic Biol Med. 1997;23(2):302-13.

Antioxidant constituents from licorice roots: isolation, structure elucidation
and antioxidative capacity toward LDL oxidation.

Vaya J, Belinky PA, Aviram M.

Migal, Galilee Technological Center, Kiryat Shmona, Israel.

The present study analyzed the antioxidative properties of natural compounds
from the root of the plant Glycyrrhiza glabra (licorice) toward LDL oxidation.
Seven constituents, with antioxidant capacity were isolated from Glycyrrhiza
glabra. The isolated compounds were identified as the isoflavans Hispaglabridin
A (1), Hispaglabridin B (4), Glabridin (3), and 4'-O-Methylglabridin (2), the
two chalcones, isoprenylchalcone derivative (5) and Isoliquiritigenin (6), and
the isoflavone, Formononetin (7). Among these compounds, Glabridin constituted
the major amount in the crude extract (11.6%, w/w) as detected by
high-performance liquid chromatography (HPLC) analysis. The antioxidative
capacities of the isolated compounds (1-7) were tested against beta-carotene
destruction and LDL oxidation. The isoflavans (1-4) at a concentration of 50
microM inhibited beta-carotene consumption, following 90 min of incubation at 50
degrees C, similar to the inhibitory effect of the whole licorice crude extract
(at 16 mg/1). The chalcones (5 and 6) exhibited moderate inhibition and the
isoflavone 7 was almost inactive, whereas vitamin E (50 microM) completely
inhibited beta-carotene consumption. The inhibitory effect of the constituents
1-7, at a concentration of 30 microM on 2,2'-azobis (2-amidinopropane)
dihydrochloride (AAPH)-induced LDL oxidation was determined by measuring the
amount of the thiobarbituric acid reactive substances (TBARS) and the amount of
lipid peroxides. While compounds 1-6 exhibited high inhibitory activity,
compound 7 and vitamin E were not active. A dose-dependent inhibitory effect of
Glabridin, on the formation of cholesteryl linoleate hydroperoxide (CLOOH), in
an AAPH-induced LDL oxidation system was also shown. Glabridin, at 5 or 40-60
microM concentration, inhibited the CLOOH formation by 62% and 90%,
respectively. These results suggest that constituents 1-6 are very potent
antioxidants toward LDL oxidation with Glabridin being the most abundant and
potent antioxidant. As LDL oxidation is a key event in the formation of the
early atherosclerotic lesion, the use of these natural antioxidants may be
proven beneficial to attenuate atherosclerosis.

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

PMID: 9199893 [PubMed - indexed for MEDLINE]

108: Immunology. 1997 Jan;90(1):115-20.

Inhibition of human complement by beta-glycyrrhetinic acid.

Kroes BH, Beukelman CJ, van den Berg AJ, Wolbink GJ, van Dijk H, Labadie RP.

Research Centre for Natural Products and Phytopharmaceuticals, Faculty of
Pharmacy, University of Utrecht, The Netherlands.

Licorice, the root extract of Glycyrrhiza glabra I., is used as a medicine for
various diseases. Anti-inflammatory as well as anti-allergic activities have
been attributed to one of its main constituents, glycyrrhizin. These activities
are mainly ascribed to the action of the aglycone, beta-glycyrrhetinic acid.
beta-Glycyrrhetinic acid has a steroid-like structure and is believed to have
immunomodulatory properties. To determine whether interference with complement
functions may contribute to the immunomodulatory activity of beta-glycyrrhetinic
acid, its effects on the classical and alternative activation pathways of human
complement were investigated. We found that beta-glycyrrhetinic acid is a potent
inhibitor of the classical complement pathway (IC50 = 35 microM), whereas no
inhibitory activity was observed towards the alternative pathway (IC50 > 2500
microM). The anticomplementary activity of beta-glycyrrhetinic acid was
dependent on its conformation, since the alpha-form was not active. It was also
established that naturally occurring steroids, e.g. hydrocortisone and
cortisone, did not inhibit human complement activity under similar conditions.
Detailed mechanistic studies revealed that beta-glycyrrhetinic acid acts at the
level of complement component C2.

PMID: 9038721 [PubMed - indexed for MEDLINE]

109: Biol Pharm Bull. 1996 Oct;19(10):1387-9.

Molecular cloning and functional expression of cDNAs for Glycyrrhiza glabra
squalene synthase.

Hayashi H, Hiraoka N, Ikeshiro Y.

Niigata College of Pharmacy, Japan.

We have isolated two cDNAs (GgSQS1 and GgSQS2) encoding squalene synthase of
Glycyrrhiza glabra L. by cross-hybridization with that of Arabidopsis thaliana
squalene synthase under conditions of low stringency. Their nucleotide sequences
contained an open reading frame for a polypeptide of 413 amino acids (GgSQS1)
and 412 amino acids (GgSQS2), respectively. The deduced amino acid sequence of
GgSQS1 exhibits 88%, 81%, 78%, 45-44%, and 45-41% identity to those of the
GgSQS2, Nicotiana benthamiana. Arabidopsis thaliana, mammal, and yeast squalene
synthases, respectively. To express the G. glabra enzymes in Escherichia coli,
the entire coding region was subcloned into an expression vector. The cell-free
extracts of E.coli transformed with the respective plasmid converted 3H-farnesyl
diphosphate into squalene.

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

PMID: 8913521 [PubMed - indexed for MEDLINE]

110: Schweiz Med Wochenschr. 1996 Jun 22;126(25):1085-98.

[Serious plant poisonings in Switzerland 1966-1994. Case analysis from the Swiss
Toxicology Information Center]

[Article in German]

Jaspersen-Schib R, Theus L, Guirguis-Oeschger M, Gossweiler B, Meier-Abt PJ.

Schweizerisches Toxikologisches Informationszentrum (STIZ), Zurich.

AIM: To analyze the types, frequency and severity of plant poisonings in
Switzerland over 29 years. METHODS: Retrospective analysis of severe poisonings
with toxic plants reported to the Swiss Toxicological Information Center (STIC).
Assessment of the causality, severity of symptoms and the types of plants
involved. RESULTS: During the period under review the STIC registered 24 950
cases of contact with or ingestion of toxic plant material. In 99.4% of all
cases the clinical course was either unknown, asymptomatic or associated with
only minor symptoms (no hospitalization). Severe plant poisonings occurred in
152 cases. Detailed analysis was possible in 135 cases (23 children, 112 adults)
including 5 lethal cases (all adults). The 24 plants involved produced the
following severe symptoms: Atropa belladonna (42 cases): anticholinergic
syndrome (42), acute psychosis (33), convulsions (2), coma (2). Heracleum
mantegazzianum (18): severe photodermatitis (18). Datura stramonium (17):
anticholinergic syndrome (17), psychosis (12), coma (2). Dieffenbachia (11):
severe stomatitis (8), corneal lesions (3). Colchicum autumnala (10): diarrhea
(10), liver necrosis (9), fatal multiorgan failure (2). Veratrum album (8):
bradycardia ( < or = 40/min) (6), shock (5). Aconitum napellus (4):
tachyarrhythmia (2), AV-block II/III (2). Aesculus hippocastanum (3): allergy
(3), anaphylactic shock (2). Hyoscyamus niger (3): anticholinergic syndrome (3).
Ricinus communis (3): diarrhea (3), toxic megacolon (1). Oenanthe crocata (2):
convulsions (1), lethal coma (1). Taxus baccata (2): tachyarrhythmia (1), fatal
asystole (1). Further single cases with severe poisonings were observed with
Arum maculatum, Asarum europaeum, Chrysanthemum vulgare, Cyclamen persicum,
Datura suaveolens, Glycyrrhiza glabra, Laburnum anagyroides, Lycopodium,
Narcissus pseudonarcissus (lethal aspiration), Nerium oleander, Senecio vulgaris
and Vicia faba. CONCLUSIONS: Potential and real intoxications with plant
materials occurred in 7.2% of all cases registered at the STIC. However, among
all plant cases only 0.6% were severe intoxications requiring hospitalization.
Although severe plant intoxications are rare events, a small number of specific
plants appear to be mainly responsible for continued serious plant poisoning in
Switzerland. The present study has identified the plants with the highest
toxicological risks and provides a data base for more rational prevention,
diagnosis and treatment of plant poisoning cases in the future.

Publication Types:
English Abstract

PMID: 8711457 [PubMed - indexed for MEDLINE]

111: Boll Chim Farm. 1996 Apr;135(4):263-6.

In vitro cytotoxic effect of some medicinal plants containing flavonoids.

Trovato A, Monforte MT, Rossitto A, Forestieri AM.

Pharmaco-Biological Department, School of Pharmacy, Messina, Italy.

Aqueous, ethanolic and petroleum ether extracts of Citrus sinensis L. (Osbeck),
Euphrasia officinalis L., Glycyrrhiza glabra L., Matricaria recutita L., Rosa
canina L. and Ruta graveolens L. have been studied. The cytotoxicity of the
drugs assayed was evaluated "in vitro" by means of the dye test using cells of
the Yoshida ascites sarcoma. The aqueous extract of Citrus sinensis L. (Osbeck);
the petroleum ether extract of Glycyrrhiza glabra L.; the ethanolic and
petroleum ether extracts of Rosa canina L. and the petroleum ether extract of
Ruta graveolens L. showed a quite significative cytotoxic effect.

PMID: 8913055 [PubMed - indexed for MEDLINE]

112: Boll Chim Farm. 1995 Dec;134(11):634-8.

[The choleretic effects of licorice: identification and determination of the
pharmacologically active components of Glycyrrhiza glabra]

[Article in Italian]

Raggi MA, Bugamelli F, Nobile L, Curcelli V, Mandrioli R, Rossetti A, Cantelli
Forti G.

Dipartimento di Scienze Farmaceutiche, Universita di Bologna.

Recent studies indicate that licorice extract, when administered per os or i.v.,
causes an evident choleretic effect in rats. Aim of this research is to identify
and quantify those licorice constituents which are responsable for the observed
choleresis. The quali-quantitative analysis of umbelliferon (7-idroxycoumarin),
was at first performed by a fluorimetric method, subsequently by a more
selective HPLC method. Moreover, this HPLC method allows the determination of
glycyrrhizin, an important licorice constituent. Unlike the glycyrrhizin, which
is present in a fairly large amount, umbelliferon resulted to be present at a
very low concentration (at trace level), both in licorice and in bile. Research
is in progress, aiming to determine the substances, beyond glycyrrhizin, which
are responsable for the choleretic effect of licorice.

Publication Types:
English Abstract

PMID: 8820979 [PubMed - indexed for MEDLINE]

113: Chem Pharm Bull (Tokyo). 1994 May;42(5):1056-62.

Chemical studies of Chinese licorice-roots. I. Elucidation of five new flavonoid
constituents from the roots of Glycyrrhiza glabra L. collected in Xinjiang.

Kitagawa I, Chen WZ, Hori K, Harada E, Yasuda N, Yoshikawa M, Ren J.

Faculty of Pharmaceutical Sciences, Osaka University, Japan.

From the air-dried roots of Glycyrrhiza glabra L. (Leguminosae) collected in
Xinjiang province, China ("Shinkyo-Kanzo" in Japanese), five new flavonoid
compounds named glucoliquiritin apioside (1) (a flavonone bisdesmoside),
prenyllicoflavone A (5) (a bisprenylflavone), shinflavone (7) (a prenylated
pyranoflavanone), shinpterocarpin (9) and 1-methoxyphaseollin (12) (both
pyranopterocarpans), were isolated together with eight known saponins, seven
known flavonoid glycosides, and eleven flavonoids. The structures of the new
compounds have been elucidated on the basis of their chemical and
physicochemical properties.

PMID: 8069956 [PubMed - indexed for MEDLINE]

114: J Pharm Pharmacol. 1994 Apr;46(4):305-9.

A novel 11 beta-hydroxysteroid dehydrogenase inhibitor contained in saiboku-to,
a herbal remedy for steroid-dependent bronchial asthma.

Homma M, Oka K, Niitsuma T, Itoh H.

Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.

To identify the inhibitor of prednisolone metabolism contained in Saiboku-To, we
conducted in-vitro experiments of 11 beta-hydroxysteroid dehydrogenase (11
beta-HSD), using rat liver homogenate and cortisol as a typical substrate. We
studied the effects of ten herbal constituents on 11 beta-HSD. Five herbal
extracts showed inhibitory activity with Glycyrrhiza glabra > Perillae
frutescens > Zizyphus vulgaris > Magnolia officinalis > Scutellaria baicalensis.
This suggests that unknown 11 beta-HSD inhibitors are contained in four herbs
other than G. glabra which contains a known inhibitor, glycyrrhizin (and
glycyrrhetinic acid). Seven chemical constituents which have been identified as
the major urinary products of Saiboku-To in healthy and asthmatic subjects were
studied; magnolol derived from M. officinalis showed the most potent inhibition
of the enzyme (IC50, 1.8 x 10(-4) M). Although this activity was less than that
of glycyrrhizin, the inhibition mechanism (non-competitive) was different from a
known competitive mechanism. These results suggest that magnolol might
contribute to the inhibitory effects of Saiboku-To on prednisolone metabolism
through inhibition of 11 beta-HSD.

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

PMID: 8051615 [PubMed - indexed for MEDLINE]

115: Steroids. 1994 Feb;59(2):127-30.

Licorice ingestion and blood pressure regulating hormones.

Schambelan M.

Department of Medicine, San Francisco General Hospital, University of California
94110.

Nearly half a century ago Revers reported that administration of a paste
prepared from succus liquiritiae, a dried watery extract of the roots of
Glycyrrhiza glabra, resulted in a reduction in abdominal symptoms as well as
radiographic evidence of healing in patients suffering from gastric ulcer.
Subsequent studies demonstrated that this preparation could prevent the
formation of gastric ulcers in experimental animals and confirmed the salutary
effects in patients, but found that approximately 20% of patients so treated
developed facial and dependent edema, often accompanied by headache, shortness
of breath, stiffness, and pain in the upper abdomen. Although these symptoms
suggested an allergic reaction, they were not accompanied by eosinophilia or
relieved by antihistamines. These untoward effects usually subsided with a
reduction of dose, although in some patients treatment had to be discontinued
entirely. Given this profile of side effects, enthusiasm for licorice as a
remedy for peptic ulcer disease soon faded. However, the popularity of licorice
flavoring in candy and in other products such as chewing tobacco persists to
this day, as do the problems in electrolyte and blood pressure homeostasis that
can occasionally occur in individuals ingesting large quantities of
licorice-containing products. Although the pattern of the renal response
suggested that the active ingredients in licorice were acting directly on the
mineralocorticoid receptors in the kidney, an even more fascinating explanation
for the toxic effects of licorice has emerged in the past decade.(ABSTRACT
TRUNCATED AT 250 WORDS)

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

PMID: 8191541 [PubMed - indexed for MEDLINE]

116: Planta Med. 1993 Dec;59(6):502-7.

Inhibition of mutagenicity in Salmonella typhimurium by Glycyrrhiza glabra
extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids.

Zani F, Cuzzoni MT, Daglia M, Benvenuti S, Vampa G, Mazza P.

Dipartimento Farmaceutico, Facolta di Farmacia, Universita di Parma, Italy.

The effects of Glycyrrhiza glabra L. extract, glycyrrhizinic acid, 18 alpha- and
18 beta-glycyrrhetinic acids on the mutagenicity of the ethyl methanesulfonate,
N-methyl-N'-nitro-N-nitrosoguanidine, and ribose-lysine Maillard model systems
were investigated by using the Salmonella/microsome reversion assay. The
protocol used allowed us to detect desmutagenic and antimutagenic activity and
to avoid false positive results due to toxicity. For all the compounds tested,
no desmutagenic activity was observed against ethyl methanesulfonate and
N-methyl-N'-nitro-N-nitrosoguanidine; only Glycyrrhiza glabra extract showed
antimutagenic activity against ethyl methanesulfonate. On using the
ribose-lysine mutagenic browning mixture, the desmutagenic activities of the
Glycyrrhiza glabra extract, glycyrrhizinic acid, 18 alpha- and 18
beta-glycyrrhetinic acids were observed. 18 beta-Glycyrrhetinic acid was the
most active compound. Glycyrrhiza glabra extract also exhibited antimutagenic
activity against ribose-lysine.

PMID: 8302947 [PubMed - indexed for MEDLINE]

117: Planta Med. 1993 Aug;59(4):351-3.

Distribution Pattern of Saponins in Different Organs of Glycyrrhiza glabra.

Hayashi H, Fukui H, Tabata M.

Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida, Kyoto 606, Japan.

Soyasaponins were detected by GC and GC-MS in different organs of GLYCYRRHIZA
GLABRA, particularly in the seed, hypocotyl and rootlet, whereas glycyrrhizin
was detected exclusively in the thickening root and the stolon. An inverse
relationship was found between the soyasaponins content and the glycyrrhizin
content in the growing stolon and in the roots at different stages of growth.

PMID: 17235989 [PubMed - in process]

118: Indian J Med Res. 1993 Apr;98:69-74.

A preliminary open trial on interferon stimulator (SNMC) derived from
Glycyrrhiza glabra in the treatment of subacute hepatic failure.

Acharya SK, Dasarathy S, Tandon A, Joshi YK, Tandon BN.

Department of Gastroenterology & Human Nutrition, All India Institute of Medical
Sciences, New Delhi.

The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC)
derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for
30 days followed by thrice weekly intravenously for 8 wk in 18 patients of
subacute hepatic failure due to viral hepatitis. The survival rate amongst these
patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per
cent in 98 patients who received supportive therapy (P < 0.01). Death in four of
the five patients was due to associated infections leading to hepatorenal
failure and terminal coma. Further studies are necessary to standardize the dose
and duration of therapy with SNMC in subacute hepatic failure.

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

PMID: 8344734 [PubMed - indexed for MEDLINE]

119: Basic Life Sci. 1993;61:65-74.

Extracellular interception of mutagens.

Shankel DM, Kuo S, Haines C, Mitscher LA.

Department of Microbiology, University of Kansas, Lawrence 66045.

Extracellular interception of mutagens by excreted enzymes or by chemical agents
that react with or bind to formed mutagens provides an important means of
defense against chemical mutagens/carcinogens. Kada and Shimoi have classified
molecules that function in this manner as "desmutagens," and many of them are
natural cellular metabolites. Among the specific mechanisms that such agents may
employ are: prevention of the activation of "promutagens" to mutagens;
stimulation of enzymes (e.g., glutathione-S-transferase) that catalyze the
binding/inactivation of damaging electrophiles; direct binding and concomitant
inactivation of promutagens or mutagens; interference with uptake of mutagens
into cells; etc. De Flora and Ramel have provided an excellent discussion of the
mechanisms of these agents and a proposed classification scheme. Drawing on work
from our own laboratories and other recent examples in the literature, several
examples of mechanistic approaches to these studies using natural plant-derived
materials, e.g., humic acid, Glycyrrhiza glabra extract, glutathione, and
bioflavonoids, are also described. Antioxidants and agents that conjugate
electrophiles will be among the modes of action described for obtaining the goal
of intercepting mutagens/carcinogens.

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

PMID: 8304956 [PubMed - indexed for MEDLINE]

120: Chem Pharm Bull (Tokyo). 1992 Sep;40(9):2487-90.

Core structure of glycyrrhizan GA, the main polysaccharide from the stolon of
Glycyrrhiza glabra var. glandulifera; anti-complementary and alkaline
phosphatase-inducing activities of the polysaccharide and its degradation
products.

Takada K, Tomoda M, Shimizu N.

Kyoritsu College of Pharmacy, Tokyo, Japan.

The controlled Smith degradation and limited hydrolysis of glycyrrhizan GA, a
representative polysaccharide with remarkable phagocytosis-enhancing activity
isolated from the stolon of Glycyrrhiza glabra L. var. glandulifera Reg. et
Herd. were carried out. Methylation analyses of the primary and the secondary
Smith degradation products and of the limited hydrolysis product indicated that
the core structural features of glycyrrhizan GA include a backbone chain
composed of beta-1,3-linked D-galactose residues. Three-fifths of the galactose
units in the backbone carry side chains composed of beta-1,3- and
beta-1,6-linked D-galactosyl residues at position 6. Anti-complementary and
alkaline phosphatase-inducing activities of the polysaccharide, periodate
oxidation-reduction and the controlled Smith degradation products were
investigated, and the controlled Smith degradation product showed significant
activity.

PMID: 1446371 [PubMed - indexed for MEDLINE]

121: Mutat Res. 1992 Jun;282(2):93-8.

Glycyrrhiza glabra extract as an effector of interception in Escherichia coli
K12+.

Kuo S, Shankel DM, Telikepalli H, Mitscher LA.

Department of Microbiology, University of Kansas, Lawrence 66045.

Glycyrrhiza glabra polar lipid extract contains a number of flavonoids and
related chemical compounds. Studies on the effectiveness of Glycyrrhiza glabra
polar lipid extract in intercepting reactive molecules generated from the
illumination of the photosensitizers rose bengal and phenosafranin indicate that
it is effective in preventing cytotoxicity against E. coli K12+ in a
dose-related fashion using illuminated rose bengal. Since only a modest
scavenging of singlet oxygen generated from phenosafranin is observed, the
effects of the extracts are less related to singlet oxygen-mediated oxidation of
substrate (type II reactions) than non-singlet oxygen-mediated oxidation of
substrate (type I reactions). Elevated levels of glutathione observed in
exponentially growing cells of E. coli K12 were also observed.

PMID: 1377357 [PubMed - indexed for MEDLINE]

122: Anal Biochem. 1992 Apr;202(1):179-87.

A strategy for discovering biologically active compounds with high probability
in traditional Chinese herb remedies: an application of saiboku-to in bronchial
asthma.

Homma M, Oka K, Yamada T, Niitsuma T, Ihto H, Takahashi N.

Division of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.

A novel strategy for discovering biologically active components in traditional
Chinese herb remedies was performed from a pharmacokinetic view. The hypothesis
was that the active compounds should appear in blood and urine with appropriate
blood concentrations and urinary excretion rates after the administration of
herbal-extract mixtures. In this research, we applied our procedures to
Saiboku-To, one of the most popular Chinese herbal medicines in Japan.
Consisting of 10 different plant extracts, it is used for the treatment of
bronchial asthma. The analytical method adopted was a rapid-flow fractionation
(RFF) for extraction-fractionation of lipophilic components in urine followed by
silica-gel high-performance liquid chromatography (HPLC) equipped with a
multichannel ultraviolet (uv) absorption detector. beta-D-Glucuronidase-treated
urine samples collected before and after the administration of Saiboku-To to
healthy and asthmatic subjects were treated with the RFF apparatus to afford
three pH-dependent fractions: strongly acidic (S), weakly acidic (W), and
neutral (N). HPLC of these fractions, monitored by the multichannel uv detector,
showed three new peaks in the postadministrative urine: one in the N fraction,
two in the W fraction, and none in the S fraction. A compound in the N fraction
was identified with authentic magnolol, a major component in Magnolia
officinalis. Two compounds in the W fraction were identified by comparison with
authentic samples as 8,9-dihydroxydihydromagnolol and liquiritigenin,
metabolites previously isolated from M. officinalis and Glycyrrhiza glabra,
respectively.

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

PMID: 1352438 [PubMed - indexed for MEDLINE]

123: Aten Primaria. 1991 Oct;8(9):733-4.

[Glycyrrhiza glabra and other herbs]

[Article in Spanish]

Alfonso Landa J, Lana Moreno JM, Tiberio Lopez G, Sanchez AJ.

Publication Types:
Case Reports
Letter

PMID: 16989064 [PubMed - indexed for MEDLINE]

124: Chem Pharm Bull (Tokyo). 1991 Aug;39(8):2082-6.

Characterization of a polysaccharide having activity on the reticuloendothelial
system from the stolon of Glycyrrhiza glabra var. glandulifera.

Shimizu N, Tomoda M, Satoh M, Gonda R, Ohara N.

Kyoritsu College of Pharmacy, Tokyo, Japan.

An acidic polysaccharide, named glycyrrhizan GA, was isolated from the stolon of
Glycyrrhiza glabra L. var. glandulifera Reg. et Herd. It produced a single band
on electrophoresis and a single peak on gel chromatography, and its molecular
mass was estimated to be 85,000. Glycyrrhizan GA is composed of L-arabinose:
D-galactose: L-rhamnose: D-galacturonic acid: D-glucuronic acid in the molar
ratio of 22:10:1:2:1, in addition to small amounts of O-acetyl groups. Part of
the hexuronic acid residues exist as methyl esters. Methylation analysis,
carbon-13 nuclear magnetic resonance and periodate oxidation studies indicated
that its structural features include mainly alpha-arabino-beta-3,6-galactan type
structural units. Glycyrrhizan GA showed remarkable reticuloendothelial
system-potentiating activity in a carbon clearance test.

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

PMID: 1797429 [PubMed - indexed for MEDLINE]

125: Pak J Pharm Sci. 1991 Jul;4(2):145-52.

Inhibition of adrenaline-induced aggregation of human platelets by Pakistani
medicinal plants.

Sajid TM, Rashid S, Saeed SA.

Department of Pharmacology, Faculty of Pharmacy, University of Karachi,
Karachi-75270, Pakistan.

The effects of extracts of Pakistani plants claiming medicinal value were
observed on adrenaline-induced aggregation of human platelets according to the
method of Born (1962). The extracts manifested significant inhibitory activity
in doses of 0.625 mgm(-1) to 2.5 mgml(-1) in this in vitro model. The potency of
the plant extracts in inhibiting platelet aggregation induced by adrenaline is
in the following order: Sida pakistanica, IC50 = 0.90 mgml(-1) > Tribulus
terrestris, IC50 = 0.97 mgml(-1) > Solanum surattense, IC50 = 1.34 mgml(-1)
Tephrosia subtriflora, IC50 = 1.40 mgml(-1) > Glycyrrhiza glabra (butanolic
extract), IC50 = 1.66 mgml(-1) > Urtica dioica IC50 = 2.17 mgml(-1). Further
studies are proposed to find out whether the inhibition of adrenaline-induced
platelet aggregation is mediated through alpha-adrenoceptor blockade or
suppressed synthesis of prostaglandin endoperoxides.

PMID: 16414694 [PubMed]

126: Nutr Cancer. 1991;15(3-4):187-93.

Inhibition of mouse skin tumor-initiating activity of DMBA by chronic oral
feeding of glycyrrhizin in drinking water.

Agarwal R, Wang ZY, Mukhtar H.

Department of Dermatology, University Hospitals of Cleveland, OH.

Licorice (Glycyrrhiza glabra), a Mediterranean plant, has been used as an
antidote, demulcent, and elixir folk medicine for generations in China. The main
water-soluble constituent of licorice is glycyrrhizin (GL), which has been shown
to possess several pharmacological properties. In this study, we show that oral
feeding of GL to Sencar mice resulted in substantial protection against skin
tumorigenesis caused by 7,12-dimethyl-benz [a]anthracene (DMBA) initiation and
12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. The latent period prior to
the onset of tumor development was considerably prolonged in GL-fed animals
compared with animals not fed GL and resulted in significant decrease in the
number of tumors per mouse, during and at the termination of the experiment.
Oral feeding of GL in drinking water also resulted in inhibition in the binding
of topically applied [3H]benzo[a]pyrene and [3H]DMBA to epidermal DNA. The
possible mechanism(s) of the antitumor-initiating activity may be due to the
involvement of GL as inhibitor of the carcinogen metabolism followed by DNA
adduct formation. Our results suggest that GL possesses considerable
antitumorigenic activity and could prove useful in protecting some forms of
human cancer.

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

PMID: 1907733 [PubMed - indexed for MEDLINE]

127: Nahrung. 1991;35(8):799-806.

Metabolic effects of licorice roots (Glycyrrhiza glabra) on lipid distribution
pattern, liver and renal functions of albino rats. MS.

Sitohy MZ, el-Massry RA, el-Saadany SS, Labib SM.

Biochemistry Department, Faculty of Agriculture, Zagazig University, Egypt.

The biochemical activity of licorice roots was investigated by administrating it
to hypercholesterolaemic rats at two different doses. High cholesterol level in
the serum and most organs of hypercholesterolaemic rats was accompanied by high
levels of triglycerides and total lipids but low one of phospholipids. The
hypocholesterolaemic action of licorice roots was accompanied by hypolipaemic
action but higher level of phospholipids in the rat serum and most organs. The
results showed that while the high cholesterol level in the rat serum has
impairing effects on liver and renal functions, the licorice administered to
these rats has a counteracting action i.e. it can improve the impaired function
of both liver and p4f1ey, It has also a hypoglycaemic action.

PMID: 1780004 [PubMed - indexed for MEDLINE]

128: Z Naturforsch [C]. 1990 Sep-Oct;45(9-10):937-41.

A further contribution to the triterpenoid constituents of Glycyrrhiza glabra L.

Elgamal MH, Hady FK, Hanna AG, Mahran GH, Duddeck H.

National Research Centre, Laboratory of Natural Products, Dokki-Cairo, Egypt.

Five pentacyclic triterpenoids have been isolated from the minor constituents of
local liquorice roots, one of them has not been isolated before from liquorice
root. Their structural formulae and stereochemical configuration was determined
by spectroscopic methods. 13C and 1H NMR data have been compiled.

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

PMID: 2291771 [PubMed - indexed for MEDLINE]

129: Basic Life Sci. 1990;52:457-60.

Specificity of antimutagens against chemical mutagens in microbial systems.

Shankel DM, Clarke CH.

University of Kansas, Lawrence.

Procedures have been developed which enable the study of antimutagenic
specificity of certain antimutagenic chemicals against chemical
mutagens/carcinogens. Modifications of the Ames Salmonella assay, the Bacillis
subtilis rec assay of Kada and co-workers, and the Luria-Delbruck fluctuation
test, along with procedures we have developed utilizing E. coli K12 strain ND160
developed by Dworkin, all are employed in these studies. Using these procedures,
a number of naturally-occurring compounds and/or their derivatives have been
shown to produce antimutagenic specificity either against changes at different
specific genetic loci or against activity of specific chemical mutagens such as
nitrofurazone, ethyl methanesulfonate, or caffeine. Compounds that demonstrate
this activity include cinnamaldehyde, chlorophyllin, an extract of Glycyrrhiza
glabra, spermine, and mixtures of guanosine and cytidine. The data demonstrate
that some antimutagens act specifically against spontaneous mutations, while
others inhibit the development of chemically-induced mutations at specific loci.
These results have potential application to the prevention of chemical
toxicological damage.

Publication Types:
Comparative Study

PMID: 2327947 [PubMed - indexed for MEDLINE]

130: Phytochemistry. 1990;29(7):2149-52.

Biotransformation of 18 beta-glycyrrhetinic acid by cell suspension cultures of
Glycyrrhiza glabra.

Hayashi H, Fukui H, Tabata M.

Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

Two biotransformation products formed from 18 beta-glycyrrhetinic acid by cell
suspension cultures of Glycyrrhiza glabra were isolated and their structures
determined by chemical and spectral data as
3-O-[alhpa-L-arabinopyranosyl-(1----2)-beta-D-Glucuronopy ranosyl]-24-
hydroxy-18 beta-glycyrrhetinic acid and 30-O-beta-D-glycopyrano-syl-18
beta-glycyrrhetinic acid. The formation of glycyrrhizin, the main triterpene
glucuronide of the licorice root, was not detected among the biotransformation
products. This is the first report of the glucuronylation of an exogenous
triterpene in plant cell cultures.

PMID: 1366692 [PubMed - indexed for MEDLINE]

131: Indian J Exp Biol. 1989 Nov;27(11):959-62.

Effect of ayurvedic medicines on beta-glucuronidase activity of Brunner's glands
during recovery from cysteamine induced duodenal ulcers in rats.

Nadar TS, Pillai MM.

Biochemical and histochemical studies revealed decreased beta-glucuronidase
activity in the Brunner's glands of duodenal ulcerated rats. The enzyme activity
showed gradual increase during recovery. Rats treated with a mixture of
Ayurvedic medicines (Glycyrrhiza glabra, Terminalia chebula, Piper longum and
Shanka Bhasma) recovered faster with concomitant increase in beta-glucuronidase
activity in the Brunner's glands. It can be concluded that Ayurvedic medicines
used do not act as antacid but improve the secretory status of Brunner's glands
involved in the protection against duodenal ulcer.

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

PMID: 2620935 [PubMed - indexed for MEDLINE]

132: Chem Pharm Bull (Tokyo). 1988 Oct;36(10):4174-6.

Two antimicrobial flavanones from the leaves of Glycyrrhiza glabra.

Fukui H, Goto K, Tabata M.

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

PMID: 3245990 [PubMed - indexed for MEDLINE]

133: Farmakol Toksikol. 1988 Jul-Aug;51(4):90-3.

[Pharmacological study of the anti-inflammatory agent glyderinine]

[Article in Russian]

Azimov MM, Zakirov UB, Radzhapova ShD.

In experiments on various animals glyderinine, a derivative of glycyrrhizic acid
isolated from Glycyrrhiza glabra, was found to exert a pronounced
anti-inflammatory effect exceeding that of hydrocortisone and amidopyrine. The
mechanism of the anti-inflammatory effect was to a certain degree related to the
adrenal cortex, suppression of vascular permeability and antagonism to
inflammation as well. Similarly to other anti-inflammatory agents, glyderinine
possesses analgesic and antipyretic properties, but unlike them it fails to
suppress hemopoiesis and to cause ulceration of the gastrointestinal mucosa. The
drug is of low toxicity and exerts the antiallergic effect. Glyderinine was
successfully tried and recommended for a wide use as an ointment for treating
skin diseases.

Publication Types:
Comparative Study
English Abstract

PMID: 3191985 [PubMed - indexed for MEDLINE]

134: Ann Pharm Fr. 1987;45(3):249-54.

[Purification of an alcoholic extract of licorice, Glycyrrhiza glabra L., by a
strain of Aspergillus niger]

[Article in French]

Texier O, Barthomeuf C, Regerat F, Pourrat H.

Publication Types:
English Abstract

PMID: 3434975 [PubMed - indexed for MEDLINE]

135: Proc Soc Exp Biol Med. 1986 Feb;181(2):205-10.

Enhancement of interferon-gamma production in glycyrrhizin-treated human
peripheral lymphocytes in response to concanavalin A and to surface antigen of
hepatitis B virus.

Shinada M, Azuma M, Kawai H, Sazaki K, Yoshida I, Yoshida T, Suzutani T, Sakuma
T.

The effects of glycyrrhizin, a component of licorice (Glycyrrhiza glabra) roots,
on the production of interferon-gamma in human peripheral lymphocyte-macrophage
cultures by concanavalin A (Con A) was examined. Interferon-gamma production in
normal lymphocyte-macrophage cultures treated with 10 to 100 micrograms/ml of
glycyrrhizin at 37 degrees C for 12 hr or longer, and then treated with 10
micrograms/ml of Con A, was enhanced four to eight times compared to control
cell cultures. Lymphocyte-macrophage cultures treated with 10 to 100
micrograms/ml of glycyrrhizin alone did not produce interferon. No significant
difference in the adsorption of [3H]Con A to glycyrrhizin-treated and control
lymphocyte-macrophage cultures was found, but RNA and protein synthesis of the
treated lymphocytes was increased compared to control cells; DNA synthesis,
however, was reduced. Collaboration between enriched T-lymphocytes and
macrophages, both treated with glycyrrhizin, was needed for the enhancement of
interferon-gamma production. A smaller increase in interferon production was
also observed in the glycyrrhizin-treated peripheral lymphocyte-macrophage
cultures derived from an asymptomatic carrier of hepatitis B virus, in response
to Con A and surface antigen of hepatitis B virus.

PMID: 3080754 [PubMed - indexed for MEDLINE]

136: Basic Life Sci. 1986;39:153-65.

Isolation and identification of higher plant agents active in antimutagenic
assay systems: Glycyrrhiza glabra.

Mitscher LA, Drake S, Gollapudi SR, Harris JA, Shankel DM.

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

PMID: 3094492 [PubMed - indexed for MEDLINE]

137: Planta Med. 1984 Oct;50(5):409-13.

Formation of glycyrrhizinic acid in Glycyrrhiza glabra var. typica.

Fuggersberger-Heinz R, Franz G.

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

PMID: 6522506 [PubMed - indexed for MEDLINE]

138: Pharm Unserer Zeit. 1983 Mar;12(2):49-54.

[Chemistry and therapeutic use of licorice (Glycyrrhiza glabra L.)]

[Article in German]

Lutomski J.

PMID: 6844364 [PubMed - indexed for MEDLINE]

139: J Ethnopharmacol. 1980 Mar;2(1):19-22.

Traditional medicine in health care.

Sayed MD.

The state of research on plants used in traditional medicine and its development
in Egypt is indicated by the number of scientific institutions devoted to this
problem: Universities, the National Research Centre, the Desert Institute and
the Horticulture Department of the Ministry of Agriculture. Moreover, the use of
certain medicinal plants has been "industrialised', e.g., Ammi visnaga,
Cymbopogon proximus, Nigella sativa and Aloe vera. Other plants are under
investigation: Urginea maritima, Phytolacca americana and Euphorbia sp. (known
for its claimed antitumour properties), Glycyrrhiza glabra, Cynara scolymus and
Solanum laciniatum.

PMID: 7464176 [PubMed - indexed for MEDLINE]

140: J Nat Prod. 1980 Mar-Apr;43(2):259-69.

Antimicrobial agents from higher plants. Antimicrobial isoflavanoids and related
substances from Glycyrrhiza glabra L. var. typica.

Mitscher LA, Park YH, Clark D, Beal JL.

Bioassay-directed fractionation of Glycyrrhiza glabra L. var. typica resulted in
the isolation and characterization of glabridin (I), glabrol (2), glabrene (3),
3-hydroxyglabrol (4), 4'-O-methylglabridin (5), 3'-methoxyglabridin (6),
formononetin (7), phaseollinisoflavan (8), hispaglabridin A (9), hispaglabridin
B (13), salicylic acid and O-acetyl salicylic acid. Of these, hispaglabridin A,
hispaglabridin B, 4'-O-methylglabridin, glabridin, glabrol and 3-hydroxyglabrol
possess significant antimicrobial activity in vitro; hispaglabridin A,
hispaglabridin B, 3'-methoxyglabridin, 4'-O-methylglabridin 3-hydroxyglabrol,
phaseollinisoflavan, salicylic acid, and O, acetyl salicylic acid are newly
found in Glycyrrhiza sp.; and hispaglabridin A, hispaglabridin B,
3'-methoxyglabridin, 4'-O-methylglabridin, and 3-hydroxyglabrol are new to the
literature and their structures are proposed herein.

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

PMID: 7381508 [PubMed - indexed for MEDLINE]

141: Nature. 1979 Oct 25;281(5733):689-90.

Glycyrrhizic acid inhibits virus growth and inactivates virus particles.

Pompei R, Flore O, Marccialis MA, Pani A, Loddo B.

Screening investigations in antiviral action of plant extracts have revealed
that a component of Glycyrrhiza glabra roots, found to be glycyrrhizie acid, is
active against viruses. We report here that this drug inhibits growth and
cytopathology of several unrelated DNA and RNA viruses, while not affecting cell
activity and ability to replicate. In addition, glycyrrhizic acid inactivates
herpes simplex virus particles irreversibly.

PMID: 233133 [PubMed - indexed for MEDLINE]

142: Ann Nutr Aliment. 1978;32(5):947-55.

[High-performance liquid-liquid chromatography in beverage analysis]

[Article in French]

Bricout J, Koziet Y, de Carpentrie B.

Liquid liquid chromatography was performed with columns packed with stationary
phases chemically bonded to silica microparticules. These columns show a high
efficiency and are used very easily. Flavouring compounds like aromatic
aldehydes which have a low volatility were analyzed in brandy using a polar
phase alkylnitrile. Sapid substances like amarogentin in Gentiana lutea or
glyryrrhizin in Glycyrrhiza glabra were determined by reversed phase
chromatography. Finally ionizable substances like synthetic dyes can be analyzed
by paired ion chromatography witha non polar stationary phase.

Publication Types:
English Abstract

PMID: 754597 [PubMed - indexed for MEDLINE]

143: Planta Med. 1975 Mar;27(2):159-63.

Constituents of local plants. XVIII. 28-hydroxyglycyrrhetic acid, a new
triterpenoid isolated from the roots of Glycyrrhiza glabra.

Elgamal MH, El-Tawil BA.

PMID: 1121529 [PubMed - indexed for MEDLINE]

144: J Pharm Belg. 1974 Nov-Dec;29(6):560-72.

[Identification of some flavonic aglycones in root extracts of Glycyrrhiza
glabra L]

[Article in French]

Hoton-Dorge M.

Publication Types:
English Abstract

PMID: 4465439 [PubMed - indexed for MEDLINE]

145: Planta Med. 1971 Nov;20(3):278-82.

Isolation of two new flavonoids from the root of Glycyrrhiza glabra var. typica.

van Hulle C, Braeckman P, Vandewalle M.

PMID: 5125495 [PubMed - indexed for MEDLINE]

146: Aptechn Delo. 1966 Jul-Aug;15(4):27-31.

[Differences between the root and rhizome of Ural licorice (Glycyrrhiza
uralensis Fisch.) and those of smooth licorice (Glycyrrhiza glabra L.)]

[Article in Russian]

Murav'ev IA, Maniak VA.

PMID: 5990577 [PubMed - indexed for MEDLINE]

147: J Indian Med Prof. 1965 Dec;12(9):5575-6.

A clinical trial of glycyrrhiza glabra in pemphigus.

Saxena RC, Gupta RN, Gupta GP, Bhargava KP.

Publication Types:
Case Reports

PMID: 5855704 [PubMed - indexed for MEDLINE]

148: Med Prom SSSR. 1964 Oct;18:20-3.

[CHEMICAL AND PHARMACEUTICAL RESEARCH ON FLAVANOIDS OF GLYCYRRHIZA GLABRA L. AND
GLYCYRRHIZA URALENSIS FISCH.]

[Article in Russian]

LITVINENKO VI, OBOLENTSEVA GV.

PMID: 14303586 [PubMed - OLDMEDLINE]

149: Pharmazie. 1964 Aug;19:538-40.

[FLUCTUATION IN THE SAPONIN CONTENT AND THE HEMOLYTIC ACTIVITY OF SAPONARIA
OFFICINALIS L., PRIMULA OFFICINALIS (L.) HILL., POLEMONIUM COERULEUM L., AND
GLYCYRRHIZA GLABRA L.]

[Article in German]

[No authors listed]

PMID: 14346279 [PubMed - OLDMEDLINE]

150: Zentralbl Veterinarmed A. 1964 Jul;11(5):476-82.

Estrogenic substances from Egyptian Glycyrrhiza glabra. II. Beta-sitosterol as
an estrogenic principle.

Zayed SM, Hassan A, Elghamry MI.

PMID: 4954505 [PubMed - indexed for MEDLINE]

151: Dokl Akad Nauk SSSR. 1964 Mar 21;155:600-2.

[CHALCONE GLYCOSIDES FROM GLYCYRRHIZA GLABRA L.]

[Article in Russian]

LITVINENKO VI.

PMID: 14236076 [PubMed - OLDMEDLINE]

152: Farmakol Toksikol. 1964 Mar-Apr;27:217-22.

[PHARMACOLOGY OF GLYCYRRHIZA GLABRA PREPARATIONS.]

[Article in Russian]

ALESHINSKAIA EE, ALESHKINA IaA, BEREZHINSKAIA VV, TRUTNEVA EA.

PMID: 14193092 [PubMed - OLDMEDLINE]

153: Zhonghua Fang She Xue Za Zhi. 1960 Apr;8:95.

[Roentgenologic changes in the heart in Addison's disease before and after
Glycyrrhiza glabra therapy.]

[Article in Chinese]

WANG ST.

PMID: 14004864 [PubMed - indexed for MEDLINE]

154: Zhonghua Wai Ke Za Zhi. 1959 Oct;7:1029-31.

[Glycyrrhiza glabra and daphne in the treatment of frostbite: preliminary
observations on 76 cases.]

[Article in Chinese]

CHANG CY.

PMID: 13809147 [PubMed - indexed for MEDLINE]

155: Indian J Psychol. 1959 Jan;3(1):39-47.

Antiarthritic activity of glycyrrhiza glabra Linn.

GUJRAL ML, SAREEN KN, TANGRI KK, ROY AK, GUPTA GP, AMMA MK.

PMID: 13653795 [PubMed - OLDMEDLINE]

156: Ann Pharm Fr. 1955 Sep-Oct;13(9-10):592-5.

[Liquiritoside, flavonoside from root of licorice, Glycyrrhiza glabra L.]

[Article in French]

PARIS R, GUILLOT M.

PMID: 13292798 [PubMed - indexed for MEDLINE]

157: Rev Med Suisse Romande. 1954 Aug;74(8):475-8.

[Licorice or Glycyrrhiza glabra.]

[Article in French]

DJABRI S.

PMID: 13195330 [PubMed - indexed for MEDLINE]

158: Therapie. 1954;9(1):68-74.

[Pharmacologic study of licorice (Glycyrrhiza glabra L.) licorice and gastric
ulcer.]

[Article in Undetermined Language]

VINCENT D.

PMID: 13187452 [PubMed - OLDMEDLINE]

159: Bratisl Lek Listy. 1953;33(4):281-91.

[Certain less known properties of Glycyrrhiza glabra.]

[Article in Undetermined Language]

MENKYNA RA.

PMID: 13093849 [PubMed - indexed for MEDLINE]

160: Pharmazie. 1952 Jul;7(7):444-8.

[Glycyrrhiza glabra L.]

[Article in Undetermined Language]

KWASNIEWSKI V.

PMID: 12983198 [PubMed - indexed for MEDLINE]

161: Therapie. 1952;7(4):337-41.

[Pharmacological study of liquorice (Glycyrrhiza glabra L.); liquorice and
histamine.]

[Article in Undetermined Language]

VINCENT D.

PMID: 12984369 [PubMed - OLDMEDLINE]

162: Therapie. 1951;6(6):448-59.

[Pharmacological study of licorice (Glycyrrhiza glabra L.); licorice and
acetylcholine.]

[Article in Undetermined Language]

VINCENT D.

PMID: 14922326 [PubMed - OLDMEDLINE]

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