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.
din_dhingra@rediffmail.com

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. a_opris@email.ro

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. din_dhingra@rediffmail.com

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.
anatom@ysu.am

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.
Fumiki.Aoki@kn.kaneka.co.jp

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.
izzetk@gop.edu.tr

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. jirenli@sina.com.cn

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. tk/​1948@pharm.teikyo/​u.ac.jp

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. florian_rauchensteiner@yahoo.de

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.
valeriadimambro@yahoo.com.br

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. mparle@rediffmail.com

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.
s.sato@faculty.chiba/​u.jp

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.
t.tokiwa@kcmi.or.jp

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. jkhwang@yonsei.ac.kr

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. hayashih@gifu/​pu.ac.jp

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. achliya@yahoo.com

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. jo.thompson/​coon@pms.ac.uk

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. din_dhingra@yahoo.com

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. cpiersen@uic.edu

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.
fukai@phar.toho/​u.ac.jp

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.
hayashih@gifu/​pu.ac.jp

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. saeedi_m_2001@yahoo.co.com

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. hayashih@gifu/​pu.ac.jp

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. ryuusuke.nakagiri@kyowa.co.jp

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. hayashih@gifu/​pu.ac.jp

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. motohiro@koto.kpu/​m.ac.jp

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. cjnam@pacific.co.kr

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 act