Clinical Studies

Abstracts are presented below for clinical studies on Gymnema.

  • Botanical Name: Gymnema Sylvestre

  • Ayurvedic Name: Meshashiringi

  • Common Name: Gymnema

Gymnema Sylvestre

Plant Phytonutrient Profile

1: J Altern Complement Med. 2007 Jan;13(1):159-76.

Algorithm for complementary and alternative medicine practice and research in
type 2 diabetes.

Bradley R, Oberg EB, Calabrese C, Standish LJ.

Bastyr University, Kenmore, WA.

Objective: To develop a model to direct the prescription of nutritional and
botanical medicines in the treatment of type 2 diabetes for both clinical and
research purposes. Methods: Available literature on nutritional and botanical
medicines was reviewed and categorized as follows:
antioxidant/anti-inflammatory; insulin sensitizer; and beta-cell
protectant/insulin secretagogue. Literature describing laboratory assessment for
glycemic control, insulin resistance, and beta-cell reserve was also reviewed
and a clinical decision tree was developed. Results: Clinical algorithms were
created to guide the use of nutritional and botanic medicines using validated
laboratory measures of glycemic control, insulin sensitivity, and beta-cell
reserve. Nutrient and botanic medicines with clinical trial research support
include coenzyme Q10, carnitine, alpha-lipoic acid, N-acetylcysteine, vitamin D,
vitamin C, vitamin E, chromium, vanadium, omega-3 fatty acids, cinnamon
(Cinnamomum cassia), fenugreek (Trigonella foenum-graecum), and gymnema (Gymnema
sylvestre). Conclusions: Clinical algorithms can direct supplementation in
clinical practice and provide research models for clinical investigation.
Algorithms also provide a framework for integration of future evidence as it
becomes available. Research funding to investigate potentially beneficial
practices in complementary medicine is critically important for optimal patient
care and safety.

PMID: 17309390 [PubMed - in process]

2: Phytochem Anal. 2006 Nov;17(6):409-13.

Extraction and quantification of gymnemic acids through gymnemagenin from callus
cultures of Gymnema sylvestre.

Kanetkar PV, Singhal RS, Laddha KS, Kamat MY.

Food Engineering and Technology Department, Institute of Chemical Technology
(ICT), University of Mumbai, Matungoa, Mumbai 400 019, Maharashtra, India.

The phyto-constituents of Gymnema sylvestre are used in the treatment of
diabetes and obesity. The present work reports on the extraction of gymnemic
acid through gymnemagenin from callus cultures of G. sylvestre. Components were
separated on pre-coated silica gel 60 GF254 plates with chloroform:methanol
(8:2) and scanned using a densitometric scanner at 205 nm in the near-UV region.
Linearity of determination of gymnemagenin was observed in the range 2-10
microg. The average percentage recovery of gymnemagenin from leaf callus
extracts was 98.9+/-0.3.

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

PMID: 17144249 [PubMed - in process]

3: Biochem Biophys Res Commun. 2006 Jul 28;346(2):386-92. Epub 2006 Jun 5.

Induction of salivary kallikreins by the diet containing a sweet-suppressive
peptide, gurmarin, in the rat.

Yamada A, Nakamura Y, Sugita D, Shirosaki S, Ohkuri T, Katsukawa H, Nonaka K,
Imoto T, Ninomiya Y.

Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu
University, Higashi-ku, Fukuoka, Japan.

Gymnema sylvestre (gymnema) contains gurmarin that selectively inhibits
responses to sweet substances in rodents. The present study investigated
possible interaction between gurmarin and the submandibular saliva in rats fed
diet containing gymnema. Electrophoretic analyses demonstrated that relative
amounts of two proteins in the saliva clearly increased in rats fed the gymnema
diet. However, rats previously given section of the bilateral glossopharyngeal
nerve showed no such salivary protein induction. Analyses of amino acid sequence
indicate that two proteins are rat kallikrein 2 (rK2) and rat kallikrein 9
(rK9). rK2 and rK9, a family of serine proteases, have a striking resemblance of
cleavage site in the protein substrates. Interestingly, gurmarin possesses
comparable residues with those rK2 and rK9 prefer. The kallikreins significantly
inhibited immunoreaction between gurmarin and antigurmarin antiserum. These
results suggest that rK2 and rK9 increased by chemosensory information for the
gymnema diet via the glossopharyngeal nerve might cleave gurmarin or at least
cause specific binding with it.

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

PMID: 16765321 [PubMed - indexed for MEDLINE]

4: Phytochem Anal. 2006 May;17(3):192-6.

Standardisation of Gymnema sylvestre R.Br. by high-performance thin-layer
chromatography: an improved method.

Raju VS, Kannababu S, Subbaraju GV.

Laila Impex Research Centre, Unit I, Phase III, Jawahar Autonagar, Vijayawada
-520 007, India.

An improved high-performance thin-layer chromatographic (HPTLC) method for the
standardisation of Gymnema sylvestre is reported. The method involves the
initial hydrolysis of gymnemic acids, the active ingredients, to a common
aglycone followed by the quantitative estimation of gymnemagenin. The present
method rectifies an error found in an HPTLC method reported recently.

PMID: 16749427 [PubMed - indexed for MEDLINE]

5: Mol Cell Biochem. 2006 May 12; [Epub ahead of print]

Decreased bodyweight without rebound and regulated lipoprotein metabolism by
gymnemate in genetic multifactor syndrome animal.

Luo H, Kashiwagi A, Shibahara T, Yamada K.

Department of Pathophysiological and Therapeutic Science, Division of Medical
Biochemistry, Faculty of Medicine, Tottori University, Yonago, 683-8503, Japan.

Objective: The aim of this work was to find obesity control method without
rebound. In our previous studies, gymnemate extracted from Gymnema sylvestre,
inhibited oleic acid absorption. The Otsuka Long-Evans Tokushima Fatty (OLETF)
rat, a genetic multifactor syndrome model, exhibits progressive overweight,
hyperlipidemia and hyperglycemia. The effect of gymnemate on obesity in OLETF
was investigated. Methods: Three groups were divided (n = 4-8): (1)
OLETF-gymnemate, gymnema water extract (containing gymnemate) diet (62.5 g/kg)
and water (2.5 g/kg) were supplied 2 weeks from 26-28 weeks, following it
general diet and water were fed 3 weeks to observe if it rebound, (2)
OLETF-control and (3) the counterpart Long-Evans Tokushima Otsuka rats as
normal-control. Results: With gymnemate treatment, the food and water intake
were decreased about 1/3 and 2/3, along with body weight reduced 57.2+/- 6.4 and
75.5+/- 6.3 g during 1 and 2 weeks respectively. In the end of experiment (3
weeks after gymnemate withdrawal), the body weight was decreased to no
significant difference with normal-control. The total cholesterol was decreased
about 1/3, moreover LDL+VLDL (low-density and very-low-density lipoprotein)
cholesterol decreased about 1/2. The proportion of HDL (high-density
lipoprotein) cholesterol to the total cholesterol was increased. The serum
triglyceride was decreased to the 1/4 of OLETF control. The level of serum
cholesterol and triglyceride was no significant difference in gymnemate group
with normal group. Conclusion: Supplementation with gymnemate promotled weight
loss by its ability to reduce hyperlipidemia, which was no withdrawal rebound:
an important discovery. Supplementation with gymnemate is a novel therapeutic
tool for weight management, especially in multifactor syndrome.

PMID: 16691318 [PubMed - as supplied by publisher]

6: Carbohydr Res. 2006 Jul 24;341(10):1697-701. Epub 2006 Apr 5.

Convergent synthesis of a trisaccharide as its 2-(trimethylsilyl)ethyl glycoside
related to the flavonoid triglycoside from Gymnema sylvestre.

Mukhopadhyay B, Field RA.

Centre for Carbohydrate Chemistry, School of Chemical Sciences and Pharmacy,
University of East Anglia, Norwich NR4 7TJ, UK.

The glycone part of the flavonoid triglycoside, kaempferol
pyranoside, has been synthesized in good yield and stereoselectivity using
N-iodosuccinimide and HClO4-silica promoted glycosylations of thioglycoside

PMID: 16603139 [PubMed - indexed for MEDLINE]

7: Yakugaku Zasshi. 2006 Mar;126(3):133-43.

Medical benefits of using natural compounds and their derivatives having
multiple pharmacological actions.

Kimura I.

Department of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences,
Toyama Medical and Pharmaceutical University, Toyama, Japan.
[email protected]

The multiple pharmacological actions of a unique compound are a prerequisite for
classifying drugs as highly efficacious, because the multiple pharmacological
actions offer the possibility of treating various symptoms of chronic diseases
as described below. 1) Sustained hyperglycemia induces macrovascular and
microvascular complications in type 2 diabetes mellitus. Antihyperglycemic
medication and the control of postprandial hyperglycemia are essentially
important for normalizing plasma glucose level. Gymnemic acid IV isolated from
Gymnema sylvestre (Asclepiadaceae) leaves has antisweet, antihyperglycemic,
glucose uptake inhibitory, and gut glycosidase inhibitory effects. Most of these
pharmacological effects may synergistically contribute to alleviating type 2
diabetes-related symptoms. 2) Diabetic skeletal and vascular smooth muscles are
hypersensitive to chemical transmitters, cytokines and autacoids. The
sensitivity of neuromuscular synapses is enhanced in diabetes, which seems to be
closely associated with neuropathy as one of the diabetic complications.
beta-Eudesmol found in Atractylodes lancea rhizome has a desensitizing channel
blocking action to nicotinic acetylcholine receptors, anti-angiogenic action in
vascular endothelium, and neuronal differentiation actions. These multiple
pharmacological actions are favorable for treating angiogenic diseases possibly
including the complications of diabetes, namely, retinopathy and nephropathy,
and cancer. 3) Nipradilol is clinically utilized as a topical antiglaucoma drug.
The ocular hypotensive effects of this compound are brought about by its alpha1
and beta-adrenergic receptor blocking actions, and nitric oxide (NO) releasing
action. NO directly activates cyclooxygenases. All these pharmacologic effects
are beneficial for treating glaucoma. The selectivity and specificity of drug
action are required for treating acute diseases, infections or for acting as
useful reagents. The pleiotropic actions of natural compounds and their
derivatives serve as important clues for developing new drugs for various
chronic diseases.

Publication Types:

PMID: 16508237 [PubMed - indexed for MEDLINE]

8: Pak J Pharm Sci. 2005 Jan;18(1):62-4.

Hypogylcemic activity of aqueous extract of some indigenous plants.

Khan B, Arayne MS, Naz S, Mukhtar N.

Department of Chemistry, University of Karachi, Karachi-75270, Pakistan.
[email protected]

Pakistan is rich in medicinally important plants and has an ancient herbal
treatment methods. Our work is based on the study of some indigenous plants
which show inhibitory effect of glucose utilization, and are in use as
hypoglycemic agent in traditional system of medicine. Gymnema sylvestre,
Momordica charantia and Eugenia jumbolana have been shown to possess
hypoglycemic activity of varying degree. The results in three different media
revealed that, hypoglycemic activity is more prominent in neutral and basic
media as compared to acidic medium.

PMID: 16431387 [PubMed - indexed for MEDLINE]

9: Int J Clin Pharmacol Res. 2005;25(3):133-44.

Efficacy of a novel calcium/potassium salt of (-)-hydroxycitric acid in weight

Preuss HG, Garis RI, Bramble JD, Bagchi D, Bagchi M, Rao CV, Satyanarayana S.

Department of Physiology and Biophysics, Georgetown University Medical Center,
Basic Science Building, Room 231 B, 4000 Reservoir Rd., N.W., Washington, DC
20057, USA. [email protected]

The weight-loss efficacy of a novel, water-soluble, calcium-potassium salt of
(-)-hydroxycitric acid (HCA-SX) was re-examined in 90 obese subjects (BMI:
30-50.8 kg/m2). We combined data from two previously reported randomized,
double-blind, placebo-controlled clinical studies in order to achieve a better
statistical evaluation based on a larger population. This re-examination of data
also allowed us to reflect more intensely on various aspects of weight loss
studies. Subjects were randomly divided into three groups: group A received a
daily dose of HCA-SX 4, 667 mg (providing 2,800 mg HCA per day); group B was
given a daily dose of a combination of HCA-SX 4,667 mg, niacin-bound chromium
(NBC) 4 mg (providing 400 microg elemental chromium), and Gymnema sylvestre
extract (GSE) 400 mg (providing 100 mg gymnemic acid); and group C received a
placebo in three equally divided doses 30-60 min before each meal. All subjects
were provided a 2,000 kcal diet/day and participated in a supervised walking
program for 30 min/day, 5 days/week. Eighty-two subjects completed the study. At
the end of 8 weeks, in group A, both body weight and BMI decreased by 5.4%,
low-density lipoprotein and triglycerides levels were reduced by 12.9% and 6.9%,
respectively, while high-density lipoprotein levels increased by 8.9%, serum
leptin levels decreased by 38%, serotonin levels increased by 44.5% and urinary
excretion of fat metabolites increased by 32-109%. Group B demonstrated similar
beneficial changes, but generally to a greater extent. No significant adverse
effects were observed. The combined results confirm that HCA-SX and, to a
greater degree, the combination of HCA-SX plus NBC and GSE reduce body weight
and BMI, suppress appetite, improve blood lipid profiles, increase serum leptin
and serotonin levels and increase fat oxidation more than placebo. We conclude
that dosage levels, timing of administration, subject compliance and
bioavailability of HCA-SX significantly affect results and that when taken as
directed, HCA-SX is a highly effective adjunct to healthy weight control.

Publication Types:
Randomized Controlled Trial

PMID: 16366421 [PubMed - indexed for MEDLINE]

10: Lipids. 2005 Aug;40(8):849-53.

Antioxidant activity of various teas against free radicals and LDL oxidation.

Ohmori R, Iwamoto T, Tago M, Takeo T, Unno T, Itakura H, Kondo K.

First Department of Internal Medicine, National Defense Medical College,
Tokorozawa, Saitama. [email protected]

Tea is a widely consumed beverage throughout the world. We assessed the
antioxidant activity of six teas, including the aqueous extracts of green tea
and oolong tea (Camellia sinensis), tochu (Eucommia ulmoides), Gymnema
sylvestre, Japanese mugwort (Artemisia princeps), and barley (Hordeum vulgare),
against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and LDL oxidation, and
examined the association of LDL oxidizability with the plasma catechin levels in
10 healthy volunteers with a single dose of 5 g green tea powder. In vitro, the
inhibitory effects of DPPH radicals and LDL oxidation were found to be strongest
in the extract of green tea and weakest in that of barley. After the ingestion
of green tea powder, the lag time increased from basal 52.2 +/- 4.1 to 60.3 +/-
4.2 min at 1 h and 59.5 +/- 4.1 min at 2 h, and then returned to the baseline
lag time (51.9 +/- 1.4 at 4 h and 52.1 +/- 4.7 min at 6 h). Regarding the plasma
catechin levels, epigallocatechingallate and epicatechingallate significantly
increased from basal 3.7 +/- 1.3 and 0.8 +/- 0.8 ng/mL to 65.7 +/- 11.6 and 54.6
+/- 12.6 ng/mL at 1 h, and 74.4 +/- 18.6 and 49.4 +/- 7.1 ng/mL at 2 h,
respectively. Green tea therefore showed the strongest antioxidant activity
among the six different teas, and the inhibitory effects of green tea on LDL
oxidation depended on the plasma catechin levels.

PMID: 16296404 [PubMed - indexed for MEDLINE]

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

Effect of Dianex, a herbal formulation on experimentally induced diabetes

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

College of Pharmaceutical Sciences, Manipal, Karnataka, India.

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

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

PMID: 16106394 [PubMed - indexed for MEDLINE]

12: Chem Senses. 2005 Jul;30(6):491-6. Epub 2005 Jun 2.

Mouse strain differences in Gurmarin-sensitivity of sweet taste responses are
not associated with polymorphisms of the sweet receptor gene, Tas1r3.

Sanematsu K, Yasumatsu K, Yoshida R, Shigemura N, Ninomiya Y.

Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu
University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Gurmarin (Gur) is a peptide that selectively inhibits responses of the chorda
tympani (CT) nerve to sweet compounds in rodents. In mice, the sweet-suppressing
effect of Gur differs among strains. The inhibitory effect of Gur is clearly
observed in C57BL/6 mice, but only slightly, if at all, in BALB/c mice. These
two mouse strains possess different alleles of the sweet receptor gene, Sac
(Tas1r3) (taster genotype for C57BL/6 and non-taster genotype for BALB/c mice),
suggesting that polymorphisms in the gene may account for differential
sensitivity to Gur. To investigate this possibility, we examined the effect of
Gur in another Tas1r3 non-taster strain, 129 X 1/Sv mice. The results indicated
that unlike non-taster BALB/c mice but similar to taster C57BL/6 mice, 129 X
1/Sv mice exhibited significant inhibition of CT responses to various sweet
compounds by Gur. This suggests that the mouse strain difference in the Gur
inhibition of sweet responses of the CT nerve may not be associated with
polymorphisms of Tas1r3.

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

PMID: 15932937 [PubMed - indexed for MEDLINE]

13: J Ethnopharmacol. 2005 Feb 28;97(2):397-403. Epub 2005 Jan 18.

Effect of Diabecon on sugar-induced lens opacity in organ culture: mechanism of

Moghaddam MS, Kumar PA, Reddy GB, Ghole VS.

Biochemistry Division, Department of Chemistry, University of Pune, Pune 411007,

Cataract is the leading cause of blindness worldwide. Apart from ageing,
diabetes has been considered to be one of the major risk factors of cataract.
The high sugar levels in diabetes may cause tissue disruption and intumescences
by osmotic changes induced via aldose reductase (AR) mediated polyol pathway.
Therefore, agents that can inhibit AR and prevent sorbitol accumulation may be
helpful to combat sugar-induced cataract. In the present study, AR inhibitory
activity of Diabecon (an herbal drug used for diabetes) was studied together
with its effect against sugar-induced lens opacity in organ culture. Diabecon
aqueous extract (DAE) showed potential inhibitory activity with an IC50 value of
10 microg/ml against rat lens AR. Incubation of goat lens with
supraphysiological concentrations of glucose (100 mM) led to the loss of lens
transparency associated with increased AR activity, decreased soluble protein
and increased protein carbonyls and glycation. Addition of DAE (0.3 mg/ml) to
the medium preserved transparency and ameliorated the decrease in lens soluble
protein due to hyperglycemia and also prevented the formation of glycated
protein. Interestingly DAE inhibited aldose reductase activity in lens incubated
with 100 mM glucose. DAE decreased protein carbonyls, prevented the loss of
beta(L)-crystallin against 100 mM of glucose. We have also demonstrated here
that most of these effects are mainly due to Gymnema sylvestre, one of the
constituent herbs of Diabecon. These results suggest that Diabecon protect the
lens against sugar-induced cataract by multiple mechanisms.

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

PMID: 15707781 [PubMed - indexed for MEDLINE]

14: Pharmazie. 2004 Nov;59(11):876-8.

Hypoglycaemic effects of some plant extracts are possibly mediated through
inhibition in corticosteroid concentration.

Gholap S, Kar A.

School of Life Sciences, Devi Ahilya University, Indore, India.

To unravel the possible mechanism of glucose lowering activity, effects of ten
different plant extracts in the regulation of serum cortisol and glucose
concentrations were evaluated in male mice. While the extracts of Inula
racemosa, Boerhaavia diffusa and Ocimum sanctum decreased the serum
concentration of both cortisol and glucose, Aegle marmelos, Azadirachta indica
and Gymnema sylvestre extracts could exhibit hypoglycaemic activity without
altering the serum cortisol concentration. It appears that the hypoglycaemic
effects of former three plant extracts are mediated through their cortisol
inhibiting potency, whereas the mechanism for other plant extracts could be
different. Lipid-peroxidation was not enhanced by any of the plant extracts
(some were in fact, antiperoxidative in nature). As I. racemosa, B. diffusa and
O. sanctum exhibited antiperoxidative, hypoglycaemic and cortisol lowering
activities, it is suggested that these three plant extracts may potentially
regulate corticosteroid induced diabetes mellitus.

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

PMID: 15587591 [PubMed - indexed for MEDLINE]

15: J Pharm Pharmacol. 2004 Nov;56(11):1435-42.

Antihyperglycaemic and antioxidant effect of hyponidd, an ayurvedic herbomineral
formulation in streptozotocin-induced diabetic rats.

Babu PS, Stanely Mainzen Prince P.

Department of Biochemistry, Annamalai University, Annamalai Nagar-608 002, Tamil
Nadu, India.

Hyponidd is a herbomineral formulation composed of the extracts of ten medicinal
plants ( Momordica charantia, Melia azadirachta, Pterocarpus marsupium,
Tinospora cordifolia , Gymnema sylvestre, Enicostemma littorale, Emblica
officinalis, Eugenia jambolana, Cassia auriculata and Curcuma longa). We have
investigated hyponidd for its possible antihyperglycaemic and antioxidant effect
in diabetic rats. Rats were rendered diabetic by streptozotocin (STZ) (45 mg
kg(-1) body weight). Oral administration of hyponidd (100 mg kg(-1) and 200 mg
kg(-1)) for 45 days resulted in significant lowered levels of blood glucose and
significant increased levels of hepatic glycogen and total haemoglobin. An oral
glucose tolerance test was also performed in experimental diabetic rats in which
there was a significant improvement in blood glucose tolerance in the rats
treated with hyponidd. Hyponidd administration also decreased levels of
glycosylated haemoglobin, plasma thiobarbituric acid reactive substances,
hydroperoxides, ceruloplasmin and alpha-tocopherol in diabetic rats. Plasma
reduced glutathione and vitamin C were significantly elevated by oral
administration of hyponidd. The effect of hyponidd at a dose of 200 mg kg(-1)
was more effective than glibenclamide (600 microg kg(-1)) in restoring the
values to near normal. The results showed that hyponidd exhibits
antihyperglycaemic and antioxidant activity in STZ-induced diabetic rats.

PMID: 15525451 [PubMed - indexed for MEDLINE]

16: Diabetes Obes Metab. 2004 Nov;6(6):458-9; author reply 460-1.

Comment on:
Diabetes Obes Metab. 2004 May;6(3):171-80.

HCA efficiency.

Heymsfield SB, Aronne LJ, Blackburn GL.

Publication Types:

PMID: 15479223 [PubMed - indexed for MEDLINE]

17: Phytochem Anal. 2004 May-Jun;15(3):164-6.

Standardisation of Gymnema sylvestre r. Br. with reference to gymnemagenin by
high-performance thin-layer chromatography.

Puratchimani V, Jha S.

Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra,
Ranchi-835 215, India. [email protected]

A simple and reproducible HPTLC method for the determination of gymnemagenin (1)
in Gymnema sylvestre has been developed. Components were separated on pre-coated
silica gel 60 F254 plates with chloroform:methanol (9:1) and scanned using a
densitometric scanner in the UV reflectance mode at 290 nm. Linearity of
determination of 1 was observed in the range 4-10 microg. The average percentage
recovery of 1 from an extract was 99.09 +/- 0.29, and the content of 1 in leaves
of the title plant was 1.61% (dry weight).

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

PMID: 15202600 [PubMed - indexed for MEDLINE]

18: Shokuhin Eiseigaku Zasshi. 2004 Feb;45(1):8-18.

[Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar

[Article in Japanese]

Ogawa Y, Sekita K, Umemura T, Saito M, Ono A, Kawasaki Y, Uchida O, Matsushima
Y, Inoue T, Kanno J.

Center for Biological Safety and Research, National Institute of Health
Sciences: 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.

A 52-week study of oral-repeated-dose toxicity for the extraction powder of
Gymnema sylvestre (GS), Indian-native genus, Metaplexis japonica, was conducted
in both genders of Wistar rats. The rats were administered a graded dose of GS
at 0.01, 0.10 and 1.00% of basal powder diet, along with a group fed solely with
the basal powder diet without GS, for 52 weeks. General conditions were recorded
daily. Body weights and food consumptions were recorded weekly up to 12 weeks,
and thereafter at longer intervals. At 26 weeks, for an intermediate
examination, and 52 weeks, for the final examination, animals were subjected to
hematology, serum chemistry, and pathological examination. None of the animals
died in the period up to 52 weeks. No exposure-related changes in body-weight,
in the food consumption, in the hematological examinations, or in the serum
biochemical examinations were recognized. No histopathological alterations were
seen. Thus, it was concluded that there was no toxic effect in rats treated with
GS at up to 1.00% in the diet for 52 weeks. The no-observable-effect level from
this study is 1.00% GS, i.e., 504 mg/kg/day for male and 563 mg/kg/day for
female as mean daily intake, for 52 weeks.

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

PMID: 15168555 [PubMed - indexed for MEDLINE]

19: Diabetes Obes Metab. 2004 May;6(3):171-80.

Comment in:
Diabetes Obes Metab. 2004 Nov;6(6):458-9; author reply 460-1.

Effects of a natural extract of (-)-hydroxycitric acid (HCA-SX) and a
combination of HCA-SX plus niacin-bound chromium and Gymnema sylvestre extract
on weight loss.

Preuss HG, Bagchi D, Bagchi M, Rao CV, Dey DK, Satyanarayana S.

Department of Physiology and Biophysics, Georgetown University Medical Center,
Georgetown, Washington, DC 20057, USA. [email protected]

AIM: The efficacy of optimal doses of highly bioavailable (-)-hydroxycitric acid
(HCA-SX) alone and in combination with niacin-bound chromium (NBC) and a
standardized Gymnema sylvestre extract (GSE) on weight loss in moderately obese
subjects was evaluated by monitoring changes in body weight, body mass index
(BMI), appetite, lipid profiles, serum leptin and excretion of urinary fat
metabolites. HCA-SX has been shown to reduce appetite, inhibit fat synthesis and
decrease body weight without stimulating the central nervous system. NBC has
demonstrated its ability to maintain healthy insulin levels, while GSE has been
shown to regulate weight loss and blood sugar levels. METHODS: A randomized,
double-blind, placebo-controlled human study was conducted in Elluru, India for
8 weeks in 60 moderately obese subjects (ages 21-50, BMI >26 kg/m(2)). Subjects
were randomly divided into three groups. Group A was administered HCA-SX 4667
mg, group B was administered a combination of HCA-SX 4667 mg, NBC 4 mg and GSE
400 mg, while group C was given placebo daily in three equally divided doses
30-60 min before meals. All subjects received a 2000 kcal diet/day and
participated in supervised walking. RESULTS: At the end of 8 weeks, body weight
and BMI decreased by 5-6% in both groups A and B. Food intake, total
cholesterol, low-density lipoproteins, triglycerides and serum leptin levels
were significantly reduced in both groups, while high-density lipoprotein levels
and excretion of urinary fat metabolites increased in both groups. A marginal or
non-significant effect was observed in all parameters in group C. CONCLUSION:
The present study shows that optimal doses of HCA-SX and, to a greater degree,
the combination of HCA-SX, NBC and GSE can serve as an effective and safe
weight-loss formula that can facilitate a reduction in excess body weight and
BMI, while promoting healthy blood lipid levels.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15056124 [PubMed - indexed for MEDLINE]

20: Carbohydr Res. 2004 Mar 15;339(4):891-5.

Two new flavonol glycosides from Gymnema sylvestre and Euphorbia ebracteolata.

Liu X, Ye W, Yu B, Zhao S, Wu H, Che C.

Department of Natural Product Chemistry, China Pharmaceutical University,
Nanjing 210009, China.

Two new flavonol glycosides, namely kaempferol
pyranoside (1) and quercetin
3-O-6"-(3-hydroxyl-3-methylglutaryl)-beta-D-glucopyranoside (2), have been
isolated from the aerial parts of Gymnema sylvestre and Euphorbia ebracteolata,
respectively. Their structures were determined on the basis of chemical and
spectroscopic methods.

PMID: 14980834 [PubMed - indexed for MEDLINE]

21: Zhong Yao Cai. 2003 Apr;26(4):305-7.

[Advances in the study on hypoglycemic constituents of Gymnema sylvestre (Retz.)

[Article in Chinese]

Jiang H.

Guangxi College of Traditional Chinese Medicine, Nanning, Guangxi Province,

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

PMID: 14631994 [PubMed - indexed for MEDLINE]

22: Fitoterapia. 2003 Dec;74(7-8):699-701.

Antimicrobial activity of Gymnema sylvestre leaf extract.

Satdive RK, Abhilash P, Fulzele DP.

Plant Biotechnology and Secondary Products Section, Nuclear Agriculture and
Biotechnology Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.

The ethanolic extract of Gymnema sylvestre leaves demonstrated antimicrobial
activity against Bacillus pumilis, B. subtilis, Pseudomonas aeruginosa and
Staphylococcus aureus and inactivity against Proteus vulgaris and Escherichia

PMID: 14630178 [PubMed - indexed for MEDLINE]

23: Pharmazie. 2003 Jun;58(6):413-5.

Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the
regulation of corticosteroid induced diabetes mellitus: involvement of thyroid

Gholap S, Kar A.

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

The efficacy of Inula racemosa (root) and Gymnema sylvestre (leaf) extracts
either alone or in combination was evaluated in the amelioration of
corticosteroid-induced hyperglycaemia in mice. Simultaneously thyroid hormone
levels were estimated by radio-immunoassay (RIA) in order to ascertain whether
the effects are mediated through thyroid hormones or not. While the
corticosteroid (dexamethasone) administration increased the serum glucose
concentration, it decreased serum concentrations of the thyroid hormones,
thyroxine (T4) and triiodothyronine (T3). Administration of the two plant
extracts either alone or in combination decreased the serum glucose
concentration in dexamethasone induced hyperglycaemic animals. However, the
administration of Inula racemosa and Gymnema sylvestre extracts in combination
proved to be more effective than the individual extracts. These effects were
comparable to a standard corticosteroid-inhibiting drug, ketoconazole. As no
marked changes in thyroid hormone concentrations were observed by the
administration of any of the plant extracts in dexamethasone treated animals, it
is further suggested that these plant extracts may not prove to be effective in
thyroid hormone mediated type II diabetes, but for steroid induced diabetes.

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

PMID: 12857006 [PubMed - indexed for MEDLINE]

24: Chem Senses. 2003 Mar;28(3):237-43.

Gurmarin suppression of licking responses to sweetener-quinine mixtures in C57BL

Murata Y, Nakashima K, Yamada A, Shigemura N, Sasamoto K, Ninomiya Y.

National Research Institute of Fisheries Science, 2-12-4, Fukuura, Kanazawa-ku,
Yokohama 236-8648, Japan.

Gurmarin (Gur) is a peptide that selectively suppresses responses of the chorda
tympani nerve to sweet substances in rats and mice. In the present study, we
examined the effect of Gur on behavioral responses to sweet substances in C57BL
mice. To accomplish this, we developed a new short-term lick test and measured
numbers of licks for 10 s for sweet substances mixed with quinine hydrochloride
(QHCl) in water-deprived mice. Numbers of licks for sucrose mixed with 1 or 3 mM
QHCl increased with increasing concentration of sucrose from 0.01 to 1.0 M. Oral
infusion with 30 micro g/ml Gur produced significant decreases in responses to
concentration series for sucrose mixed with 3 mM QHCl, whereas no such effect by
Gur was observed in responses to QHCl alone or QHCl-mixed HCl, NaCl or
monosodium glutamate. The Gur suppression of QHCl-mixed sucrose responses, which
otherwise lasted for 2-3 h, rapidly returned to approximately 80% of control
levels after oral infusion with beta-cyclodextrin. These results are comparable
to neural data previously found in chorda tympani responses, and thereby provide
further evidence for Gur as a sweet response inhibitor in C57BL mice. In the
other aspect, our newly developed short-term test can also provide a tool for
measurements of taste-guided behavioral responses to sweeteners.

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

PMID: 12714446 [PubMed - indexed for MEDLINE]

25: J Neurophysiol. 2003 Aug;90(2):911-23. Epub 2003 Apr 17.

Differential gurmarin suppression of sweet taste responses in rat solitary
nucleus neurons.

Lemon CH, Imoto T, Smith DV.

Department of Anatomy and Neurobiology, University of Tennessee College of
Medicine, Memphis, Tennessee 38163, USA. [email protected]

We examined the effect of the sweet transduction blocker gurmarin on taste
responses recorded from neurons in the rat solitary nucleus (NST) to determine
how gurmarin sensitivity is distributed across neuronal type. Initially,
responses evoked by washing the anterior tongue and palate with 0.5 M sucrose,
0.1 M NaCl, 0.01 M HCl, and 0.01 M quinine-HCl were recorded from 35 neurons.
For some cells, responses to a sucrose concentration series (0.01-1.0 M) or an
array of sweet-tasting compounds were also measured. Gurmarin (10 microg/ml, 2-4
ml) was then applied to the tongue and palate. Stimuli were reapplied after
10-15 min. Neurons were segregated into groups based on similarities among their
initial response profiles using hierarchical cluster analysis (HCA). Results
indicated that sucrose responses recorded from neurons representative of each
HCA-defined class were suppressed by gurmarin. However, a disproportionate
percentage of cells in each group displayed sucrose responses that were
substantially attenuated after gurmarin treatment. Postgurmarin sucrose
responses recorded from neurons that composed 57% of class S, 40% of class N,
and 33% of class H were suppressed by >or=50% relative to control. On average,
attenuation was statistically significant only in class S and N neurons.
Although the magnitude of gurmarin-induced response suppression did not differ
across sucrose concentration, responses to different sweet-tasting compounds
were differentially affected. Responses to NaCl, HCl, or quinine were not
suppressed by gurmarin. Results suggest that information from gurmarin-sensitive
and -insensitive receptor processes converges onto single NST neurons.

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

PMID: 12702710 [PubMed - indexed for MEDLINE]

26: Diabetes Care. 2003 Apr;26(4):1277-94.

Systematic review of herbs and dietary supplements for glycemic control in

Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS.

Division for Research and Education in Complementary and Integrative Medical
Therapies, Harvard Medical School, Boston, Massachusetts, USA.
[email protected]

OBJECTIVE: To conduct a systematic review of the published literature on the
efficacy and safety of herbal therapies and vitamin/mineral supplements for
glucose control in patients with diabetes. RESEARCH DESIGN AND METHODS: We
conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane
Library Database, and HealthSTAR, from database inception to May 2002, in
addition to performing hand searches and consulting with experts in the field.
Available clinical studies published in the English language that used human
participants and examined glycemic control were included. Data were extracted in
a standardized manner, and two independent investigators assessed methodological
quality of randomized controlled trials using the Jadad scale. RESULTS: A total
of 108 trials examining 36 herbs (single or in combination) and 9
vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired
glucose tolerance, met the inclusion criteria and were analyzed. There were 58
controlled clinical trials involving individuals with diabetes or impaired
glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies
involved patients with type 2 diabetes. Heterogeneity and the small number of
studies per supplement precluded formal meta-analyses. Of these 58 trials, the
direction of the evidence for improved glucose control was positive in 76% (44
of 58). Very few adverse effects were reported. CONCLUSIONS: There is still
insufficient evidence to draw definitive conclusions about the efficacy of
individual herbs and supplements for diabetes; however, they appear to be
generally safe. The available data suggest that several supplements may warrant
further study. The best evidence for efficacy from adequately designed
randomized controlled trials (RCTs) is available for Coccinia indica and
American ginseng. Chromium has been the most widely studied supplement. Other
supplements with positive preliminary results include Gymnema sylvestre, Aloe
vera, vanadium, Momordica charantia, and nopal.

Publication Types:

PMID: 12663610 [PubMed - indexed for MEDLINE]

27: Pharmazie. 2003 Jan;58(1):5-12.

An overview on the advances of Gymnema sylvestre: chemistry, pharmacology and

Porchezhian E, Dobriyal RM.

Dabur Research Foundation, Sahibabad, India.

Chemistry and pharmacology of Gymnema sylvestre is reviewed relying on research
papers and patent literature. Extracts of this plant are widely used in
Australian, Japananese, Vietnamese and Indian folk medicine. Gymnema
preparations have a profound action on the modulation of taste, particularly
suppressing sweet taste sensations. It is used in the treatment of diabetes
mellitus and in food additives against obesity and caries. Anti-allergic,
antiviral, lipid lowering and other effects are also reported. From a
technological point of view, muchefforts have been made to mask the biter taste
of Gymnema preparations.

Publication Types:

PMID: 12622244 [PubMed - indexed for MEDLINE]

28: J Ethnopharmacol. 2002 Jun;81(1):81-100.

Medicinal plants of India with anti-diabetic potential.

Grover JK, Yadav S, Vats V.

Department of Pharmacology, All India Institute of Medical Sciences, Ansari
Nagar, New Delhi-110049, India. [email protected]

Since ancient times, plants have been an exemplary source of medicine. Ayurveda
and other Indian literature mention the use of plants in treatment of various
human ailments. India has about 45000 plant species and among them, several
thousands have been claimed to possess medicinal properties. Research conducted
in last few decades on plants mentioned in ancient literature or used
traditionally for diabetes have shown anti-diabetic property. The present paper
reviews 45 such plants and their products (active, natural principles and crude
extracts) that have been mentioned/used in the Indian traditional system of
medicine and have shown experimental or clinical anti-diabetic activity. Indian
plants which are most effective and the most commonly studied in relation to
diabetes and their complications are: Allium cepa, Allium sativum, Aloe vera,
Cajanus cajan, Coccinia indica, Caesalpinia bonducella, Ficus bengalenesis,
Gymnema sylvestre, Momordica charantia, Ocimum sanctum, Pterocarpus marsupium,
Swertia chirayita, Syzigium cumini, Tinospora cordifolia and Trigonella foenum
graecum. Among these we have evaluated M. charantia, Eugenia jambolana, Mucuna
pruriens, T. cordifolia, T. foenum graecum, O. sanctum, P. marsupium, Murraya
koeingii and Brassica juncea. All plants have shown varying degree of
hypoglycemic and anti-hyperglycemic activity.

Publication Types:

PMID: 12020931 [PubMed - indexed for MEDLINE]

29: Chem Senses. 2002 May;27(4):353-65.

Taste suppression following lingual capsaicin pre-treatment in humans.

Simons CT, O'Mahony M, Carstens E.

Section of Neurobiology, Physiology and Behavior, University of California, 1
Shields Avenue, Davis, CA 95616, USA.

The effect of oral capsaicin on taste sensations in humans was reinvestigated
with attention to methodological issues raised in previous studies, including
the mode of presentation and temperature of the tastant stimulus, as well as the
sensitizing and desensitizing properties of capsaicin. One-half of the dorsal
anterior tongue was pre-treated with capsaicin, followed by bilateral tastant
application (sucrose, NaCl, quinine, monosodium glutamate and citric acid).
Subjects indicated on which side the taste intensity was greater in a
two-alternative, forced-choice procedure and also rated taste intensity
independently on each side of the tongue. Each of the five tastants was tested
sequentially, with reapplication of capsaicin between trials in order to
maintain a constant level of burn. Four experiments were conducted: (i) a high
concentration (33 p.p.m.) (109 microM) capsaicin effect on taste intensity
elicited by high tastant concentrations; (ii) a high concentration capsaicin
effect on taste intensity elicited by low tastant concentrations; (iii) a low
concentration (1.5 p.p.m.) (4.9 microM) capsaicin effect on taste intensity
elicited by low tastant concentrations; and (iv) validation of the method for
localizing taste by pre-treating one side of the tongue with Gymnema sylvestre,
followed by bilateral application of sucrose. In the first experiment, a
significant proportion of the subjects chose the non-treated side in the
two-alternative, forced-choice procedure and assigned significantly higher
ratings to that side for sucrose-induced sweetness, quinine-induced bitterness
and glutamate-induced umami sensations. Salty and sour sensations were not
different between sides. A 15 min break was imposed in order to allow the
capsaicin burn to disappear and desensitization to set in, followed by
reapplication of the tastant test solutions. There were no bilateral differences
in the intensity of the sensations elicited by any of the five tastants. Similar
results were obtained in experiments 2 and 3. In the fourth experiment, all 15
subjects tested chose the side not treated with Gymnema sylvestre as having a
stronger sweet taste and assigned significantly higher ratings to that side,
thereby validating the method for taste localization. These results indicate
that oral capsaicin reduces certain but not all taste sensations and are
discussed in terms of possible physiological and cognitive interactions.

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

PMID: 12006375 [PubMed - indexed for MEDLINE]

30: Can J Physiol Pharmacol. 2001 Oct;79(10):836-40.

Beta-cyclodextrin inhibits the sweet taste suppressing activity of gurmarin by
the formation of an inclusion complex with aromatic residues in gurmarin.

Imoto T, Sasamoto K, Ninomiya Y.

Department of Physiology, Faculty of Medicine, Tottori University, Yonago,
Japan. [email protected]

Our recent study in mice revealed that the inhibitory activity of gurmarin on
the sweet taste responses was reduced significantly by the presence of
beta-cyclodextrin (beta-CD). To investigate the mechanism involved in the action
of beta-CD, physicochemical experiments were performed on the interaction of CDs
with gurmarin examining the effect of CDs on the UV absorption spectrum of
gurmarin and on the elution behavior in gel filtration (or exclusion)
chromatography. Among the three kinds of cyclodextrins tested, beta-CD induced
significant changes in the UV absorption spectrum of gurmarin that were
characteristic of those found in the inclusion complex formation of tyrosine and
tryptophan with beta-CD. The abnormal retention behavior of gurmarin in gel
filtration resulting from hydrophobic interaction with the gel matrix reverted
to normal in the presence of beta-CD in the elution buffer. These results
suggest that the unique domain of gurmarin, in which five aromatic amino acid
residues are all directed outwardly and form a hydrophobic cluster, is a
possible site of interaction with the gurmarin-sensitive sweet taste receptor
molecules in rodents.

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

PMID: 11697741 [PubMed - indexed for MEDLINE]

31: Eur J Nutr. 2001 Jun;40(3):127-33.

Investigations on possible serotonergic involvement in effects of OB-200G
(polyherbal preparation) on food intake in female mice.

Kaur G, Kulkarni SK.

Pharmacology Division, Univ Inst Pharm Sci, Panjab University, Chandigarh,

BACKGROUND: OB-200G is a polyherbal preparation containing aqueous extracts of
Garcinia cambogia, Gymnema sylvestre, Zingiber officinale, Piper longum and
resin from Commiphora mukul, all possessing thermogenic properties. Our previous
studies reveal OB-200G to exert antiobesity effects in dietary animal models of
obesity. AIM OF THE STUDY: The present study investigated the possible
involvement of serotonergic system in the effect of OB-200G on food intake. We
examined the effects of systemic pretreatment with 5-HT depletor,
p-chlorophenylalanine (PCPA, 300 mg/kg, i. p. for 6 days), 5-HT1A agonist,
(8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT, 0.1 mg/kg, i. p.),
nonselective 5-HT antagonist, cyproheptadine (1 mg/kg, i. p.), 5-HT2 receptor
antagonist, seganserin (1 and 2 mg/kg, i. p.) and 2-deoxy-D-glucose (2-DG,
glucose antimetabolite, 500 mg/kg, i. p.) on satiety induced by OB-200G (500
mg/kg, p. o.) in non-deprived female mice. The results were compared with
fluoxetine (10 mg/kg, i. p.), a selective serotonin reuptake inhibitor. METHODS:
Fifteen minutes after the last drug administration, groups of mice were
presented with sweetened chow and the amount of food consumed was recorded at
0.5,1,2, 3 and 4h time intervals. RESULTS: The hyperphagic effect of PCPA,
8-OH-DPAT, cyproheptadine and 2-DG was significantly (p < 0.05) antagonized by
both OB-200G and fluoxetine. However, the anorectic effect of fluoxetine was not
reversed by centrally acting 5-HT2 antagonist, seganserin but the latter
markedly attenuated the satiety action of OB-200G. CONCLUSION: The present
observations suggest the role of serotonin in mediation of satiety by OB-200G
and hence its antiobesity effect.

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

PMID: 11697445 [PubMed - indexed for MEDLINE]

32: J Nutr Sci Vitaminol (Tokyo). 2001 Apr;47(2):161-6.

Behavioral taste similarities and differences among monosodium L-glutamate and
glutamate receptor agonists in C57BL mice.

Nakashima K, Katsukawa H, Sasamoto K, Ninomiya Y.

Department of Chemistry, Asahi University School of Dentistry, Motosu-gun, Gifu,
Japan. [email protected]

Monosodium L-glutamate (MSG) and 5'-ribonucleotides elicit umami taste in humans
and probably in some species of animals. Previous studies suggest that
taste-mGluR4 and NMDA receptor may be involved in taste transduction for umami,
but behavioral responses in rats do not support the involvement of NMDA
receptor. In the present study, behavioral similarities and differences among
MSG, mGluR4 agonist L(+)-2-amino-4-phosphonobutyrate (L-AP4), and NMDA receptor
agonist N-methyl-D-aspartate (NMDA) were compared in C57BL mice by using a
conditioned taste aversion paradigm. Mice conditioned to avoid either MSG or 10
mM L-AP4 appeared to avoid MSG, disodium 5'-inosinate (IMP), a mixture of MSG
and IMP, and L-AP4, but not NMDA. Aversive conditioning to either sucrose or
NMDA was generalized only to a mixture of MSG+IMP or NaCl. However, aversive
conditioning to L-AP4 at 1 mM was generalized to NMDA and the umami substances.
Lick rates for L-AP4 increased by mixing with
(RS)-alpha-cycloprophy-4-phosphonophenylglycine (mGluR4 antagonist) when animals
were conditioned to avoid MSG or L-AP4. Lick rates for NMDA also either
decreased or increased by mixing with glycine (NMDA receptor coagonist) or
D(-)-2-amino-5-phosphonopentanoic acid (NMDA receptor antagonist) when animals
were conditioned to avoid L-AP4 or NMDA. In sucrose-conditioned mice. gurmarin
(a sweet inhibiting peptide) suppressed the avoidance of sucrose and a mixture
of MSG and IMP, but not L-AP4 and NMDA. The results suggest the possibility that
to C 57BL mice MSG may taste similar to L-AP4 but different from NMDA, although
both types of glutamate receptors as well as gurmarin-sensitive sweet receptor
may be involved in perception of umami taste.

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

PMID: 11508708 [PubMed - indexed for MEDLINE]

33: J Nat Prod. 2001 Feb;64(2):232-5.

Antisweet saponins from Gymnema sylvestre.

Ye W, Liu X, Zhang Q, Che CT, Zhao S.

Department of Chemistry, Hong Kong University of Science and Technology, Clear
Water Bay, Hong Kong.

Three new oleanane-type triterpene glycosides (1-3), along with the sodium salt
of alternoside II (4), were isolated from an ethanol extract of the leaves of
Gymnema sylvestre. The structures of these new saponins were identified as 21
3-O-beta-D-glucopyranosyl(1-->3)-beta-D-glucuronopyranoside (1), the potassium
salt of longispinogenin
3-O-beta-D-glucopyranosyl(1-->3)-beta-D-glucuronopyranoside (2), and the
potassium salt of 29-hydroxylongispinogenin
3-O-beta-D-glucopyranosyl(1-->3)-beta-D-glucuronopyranoside (3). The aglycon of
3, gymnemagenol (3a), was characterized as 3 beta,16 beta,28,
29-tetrahydroxyolean-12-ene. Structure elucidation was accomplished by
interpretation of NMR (DQF-COSY, HMQC, and HMBC) results, FABMS, and hydrolysis.
Saponin 1 and the sodium salt of alternoside II (4) exhibited antisweet

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

PMID: 11430009 [PubMed - indexed for MEDLINE]

34: Biol Pharm Bull. 2001 Jun;24(6):713-7.

Effect of administration with the extract of Gymnema sylvestre R. Br leaves on
lipid metabolism in rats.

Shigematsu N, Asano R, Shimosaka M, Okazaki M.

Biosci. Textile Technol., Shinshu University, Ueda, Nagano, Japan.
[email protected]

Extract of Gymnema sylvestre R. Br leaves (GE) was orally administered once a
day to rats fed a high fat diet or normal fat diet for 3 weeks to investigate
its influence on lipid metabolism. As a result, GE did not influence body weight
gain or feed intake in both diet groups during the experimental period. The
apparent fat digestibility was significantly decreased by GE in both diet groups
for the last 2 weeks of the experimental period, though not the apparent protein
digestibility. In addition, the excretion of neutral sterols and acid steroids
into feces was increased by GE in both diet groups. Furthermore, GE decreased
the total cholesterol and triglyceride levels in serum. On the other hand, blood
lecithin-cholesterol acyltransferase (LCAT) activity was increased by GE.
Moreover, it was suggested that GE influenced cecal fermentation and that
propionic acid and acetic acid contents in cecum were significantly increased by
GE. Consequently, it was suggested that GE improved serum cholesterol and
triglyceride levels through influence over a wide range of lipid metabolism in

PMID: 11411567 [PubMed - indexed for MEDLINE]

35: Biol Pharm Bull. 2001 Jun;24(6):643-9.

Effect of long term-administration with Gymnema sylvestre R. BR on plasma and
liver lipid in rats.

Shigematsu N, Asano R, Shimosaka M, Okazaki M.

Biosci. Textile Technol., Shinshu University, Ueda, Nagano, Japan.
[email protected]

Extract of Gymnema sylvestre leaves was administered to rats receiving either a
high fat diet or normal fat diet for 10 weeks to investigate its influence on
plasma and liver lipids and on visceral fat accumulation. In addition, its
effect was compared with those of chitosan and the influence of combined use of
these two substances was also evaluated. Within the high fat diet groups, the
extract suppressed body weight gain and accumulation of liver lipids to the same
extent as chitosan and the combined use. In addition, intraperitoneal fat and
fat drop vacuoles on the epithelium of renal tubules, noted in the high fat diet
group, were scattered by administration of the extract with the same results as
for chitosan and combined use. Within the normal fat diet groups, plasma
triglyceride levels decreased by administration of the extract, with similar
results as chitosan and combined use. Concerning plasma total cholesterol, there
was no decreasing effects with the extract, as found with chitosan and combined
use. However, the effect of chitosan on plasma total cholesterol tended to be
enhanced when used in combination with the extract. In addition, long-term
administration of the extract did not show any influence on hematological and
blood chemical parameters.

PMID: 11411552 [PubMed - indexed for MEDLINE]

36: Zhong Yao Cai. 2001 Feb;24(2):95-7.

[The pharmacognostical identification of peel of Gymnema sylvestre]

[Article in Chinese]

Zhen H, Xu S, Pan X.

Guangxi College of Traditional Chinese Medicine, Nanning 530001.

This paper reported the descriptions, microscopic UV and TLC identification of
peel of Gymnema sylvestre.

Publication Types:
English Abstract

PMID: 11402738 [PubMed - indexed for MEDLINE]

37: J Asian Nat Prod Res. 2000;2(4):321-7.

Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema
sylvestre leaves in streptozotocin-diabetic mice.

Sugihara Y, Nojima H, Matsuda H, Murakami T, Yoshikawa M, Kimura I.

Department of Chemical Pharmacology, Toyama Medical and Pharmaceutical
University, Sugitani, Japan.

We investigated the antihyperglycemic action of a crude saponin fraction and
five triterpene glycosides (gymnemic acids I-IV and gymnemasaponin V) derived
from the methanol extract of leaves of Gymnema sylvestre R. BR. (Asclepiadaceae)
in streptozotocin (STZ)-diabetic mice. The saponin fraction (60mg/kg) reduced
blood glucose levels 2 4h after the intraperitoneal administration. Gymnemic
acid IV, not the other 4 glycosides at doses of 3.4-13.4mg/kg reduced the blood
glucose levels by 13.5-60.0% 6h after the administration comparable to the
potency of glibenclamide, and did not change the blood glucose levels of normal
mice. Gymnemic acid IV at 13.4 mg/kg increased plasma insulin levels in
STZ-diabetic mice. Gymnemic acid IV (1 mg/mL) did not inhibit alpha-glycosidase
activity in the brush border membrane vesicles of normal rat small intestines.
These results indicate that insulin-releasing action of gymnemic acid IV may
contribute to the antihyperglycemic effect by the leaves of G. sylvestre.
Gymnemic acid IV may be an anti-obese and antihyperglycemic pro-drug.

PMID: 11249615 [PubMed - indexed for MEDLINE]

38: Am J Physiol Regul Integr Comp Physiol. 2000 Jun;278(6):R1513-7.

Inhibitory effect of gurmarin on palatal taste responses to amino acids in the

Harada S, Kasahara Y.

Department of Oral Physiology, Kagoshima University Dental School, 8-35-1
Sakuragaoka, Kagoshima 890-8544, Japan. [email protected]

Gurmarin (10 microg/ml), a protein extracted from Gymnema sylvestre, depressed
significantly (40-50%) the phasic taste responses to sugars (sucrose, fructose,
lactose, and maltose) and saccharin sodium recorded from the greater superficial
petrosal nerve (GSP) innervating palatal taste buds in the rat. However, no
significant effect of gurmarin was observed for taste responses to NaCl, HCl,
and quinine hydrochloride. Phasic responses to D-amino acids that taste sweet to
humans (His, Asn, Phe, Gln) were also depressed, but gurmarin treatment was
without significant effect on taste responses to D-Trp and D-Ala, six L-amino
acids (His, Asn, Phe, Gln, Trp, and Ala), and two basic amino acid HCl salts
(Arg and Lys). With the exception of D-Trp, these inhibitory effects of gurmarin
on GSP taste responses were related to the rat's preference for these

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

PMID: 10848518 [PubMed - indexed for MEDLINE]

39: Phytochemistry. 2000 Apr;53(8):893-9.

Oleanane saponins from Gymnema sylvestre.

Ye WC, Zhang QW, Liu X, Che CT, Zhao SX.

Department of Chemistry, Hong Kong University of Science and Technology, Clear
Water Bay, Kowloon, Hong Kong.

Six oleanane-type saponins, along with two known triterpene saponins, were
isolated from the leaves of Gymnema sylvestre. The structures of the oleanane
triterpene glycosides were characterized as longispinogenin
3-O-beta-D-glucuronopyranoside, 21 beta-benzoylsitakisogenin
3-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl oleanolic acid
28-O-beta-D-glucopyranosyl ester, oleanolic acid
glucopyranoside, 3-O-beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl
(1-->6)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester
and 3-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl oleanolic acid
28-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester on the basis of
hydrolysis and spectral evidence, including 1D- and 2D-NMR (TOCSY, ROESY, HMQC
and HMBC) and FABMS analyses.

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

PMID: 10820799 [PubMed - indexed for MEDLINE]

40: J Ethnopharmacol. 1999 Nov 30;67(3):367-72.

A comparative evaluation of some blood sugar lowering agents of plant origin.

Chattopadhyay RR.

Biometry Research Unit, Indian Statistical Institute, Calcutta.

A comparison of blood sugar lowering activity of four important medicinal plants
(Azadirachta indica, Gymnema sylvestre, Catharanthus roseus and Ocimum sanctum)
were carried out against normal and streptozotocin-induced diabetic rat models.
The plant extracts decreased the blood sugar level in varying degrees. Blood
sugar lowering unit (BLU) of activity of each leaf extract and tolbutamide was
calculated by ED50 values. Statistical analysis revealed significant (P < 0.05)
variation among the treatments as well as doses with regard to their blood sugar
lowering capacity. A. indica leaf extract was found to have the most potent
blood sugar-lowering activity followed by C. roseus, G. sylvestre and O.

Publication Types:
Comparative Study

PMID: 10617074 [PubMed - indexed for MEDLINE]

41: J Endocrinol. 1999 Nov;163(2):207-12.

Gymnema sylvestre stimulates insulin release in vitro by increased membrane

Persaud SJ, Al-Majed H, Raman A, Jones PM.

Physiology Division, School of Biomedical Sciences, King's College, London, UK.

To determine whether extracts of Gymnema sylvestre may have therapeutic
potential for the treatment of non-insulin-dependent diabetes mellitus (NIDDM),
we examined the effects of an alcoholic extract of G. sylvestre (GS4) on insulin
secretion from rat islets of Langerhans and several pancreatic beta-cell lines.
GS4 stimulated insulin release from HIT-T15, MIN6 and RINm5F beta-cells and from
islets in the absence of any other stimulus, and GS4-stimulated insulin
secretion was inhibited in the presence of 1 mM EGTA. Blockade of
voltage-operated Ca(2+) channels with 10 microM isradipine did not significantly
affect GS4-induced secretion, and insulin release in response to GS4 was
independent of incubation temperature. Examination of islet and beta-cell
integrity after exposure to GS4, by trypan blue exclusion, indicated that
concentrations of GS4 that stimulated insulin secretion also caused increased
uptake of dye. Two gymnemic acid-enriched fractions of GS4, obtained by size
exclusion and silica gel chromatography, also caused increases in insulin
secretion concomitant with increased trypan blue uptake. These results confirm
the stimulatory effects of G. sylvestre on insulin release, but indicate that
GS4 acts by increasing cell permeability, rather than by stimulating exocytosis
by regulated pathways. Thus the suitability of GS4 as a potential novel
treatment for NIDDM can not be assessed by direct measurements of beta-cell
function in vitro.

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

PMID: 10556769 [PubMed - indexed for MEDLINE]

42: Eur J Biochem. 1999 Sep;264(2):525-33.

High-resolution solution structure of gurmarin, a sweet-taste-suppressing plant

Fletcher JI, Dingley AJ, Smith R, Connor M, Christie MJ, King GF.

Department of Biochemistry, University of Sydney, Australia.

Gurmarin is a 35-residue polypeptide from the Asclepiad vine Gymnema sylvestre.
It has been utilised as a pharmacological tool in the study of sweet-taste
transduction because of its ability to selectively inhibit the neural response
to sweet tastants in rats. We have chemically synthesised and folded gurmarin
and determined its three-dimensional solution structure to high resolution using
two-dimensional NMR spectroscopy. Structure calculations utilised 612
interproton-distance, 19 dihedral-angle, and 18 hydrogen-bond restraints. The
structure is well defined for residues 3-34, with backbone and heavy atom rms
differences of 0.27 +/- 0.09 A and 0.73 +/- 0.09 A, respectively. Gurmarin
adopts a compact structure containing an antiparallel beta-hairpin (residues
22-34), several well-defined beta-turns, and a cystine-knot motif commonly
observed in toxic and inhibitory polypeptides. Despite striking structural
homology with delta-atracotoxin, a spider neurotoxin known to slow the
inactivation of voltage-gated Na+ channels, we show that gurmarin has no effect
on a variety of voltage-sensitive channels.

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

PMID: 10491100 [PubMed - indexed for MEDLINE]

43: Chem Senses. 1999 Aug;24(4):387-92.

Induction of salivary gurmarin-binding proteins in rats fed gymnema-containing

Katsukawa H, Imoto T, Ninomiya Y.

Department of Oral Physiology, School of Dentistry, Asahi University, Hozumi,
Gifu, Japan. [email protected]

Gymnema sylvestre, a tropical plant, contains gurmarin that selectively
suppresses sucrose responses of the chorda tympani nerve in rats and mice. We
investigated preference for taste solutions and saliva composition in rats fed a
diet containing this plant (gymnema diet). Preference for 0.01 M sucrose and a
mixture of 0.03 M sucrose and 0.03 mM quinine-HCl significantly decreased at 1-2
days after the start of the gymnema diet and subsequently returned closely to
the control levels within about a week. There was no significant change in
preference for NaCl, monosodium glutamate and quinine-HCl during feeding trials.
Submandibular saliva of rats fed the gymnema diet for 4 and 14 days showed an
inhibitory effect on immunoreaction between gurmarin and antigurmarin serum.
Analyses using electrophoresis and affinity chromatography indicated that the
saliva contains gurmarin binding proteins with molecular weights of 15, 16, 45,
60 and 66 kDa. These results suggest that reduction of preference for sucrose
was probably caused by gurmarin contained in the gymnema diet and subsequent
restoration of the preference may be due to suppression of the effect of
gurmarin by salivary gurmarin-binding proteins induced by the gymnema diet.

PMID: 10480674 [PubMed - indexed for MEDLINE]

44: J Neurophysiol. 1999 Jun;81(6):3087-91.

Sweet taste responses of mouse chorda tympani neurons: existence of
gurmarin-sensitive and -insensitive receptor components.

Ninomiya Y, Imoto T, Sugimura T.

Department of Oral Physiology, Asahi University School of Dentistry, Gifu
501-0296, Japan.

Inhibitory effects of gurmarin (gur) on responses to sucrose and other
sweeteners of single fibers of the chorda tympani nerve in C57BL mice were
examined. Of 30 single fibers that strongly responded to 0. 5 M sucrose but were
not or to lesser extent responsive to 0.1 M NaCl, 0.01 M HCl, and 0.02 M quinine
HCl (sucrose-best fibers), 16 fibers showed large suppression of responses to
sucrose and other sweeteners by lingual treatment with 4.8 microM (approximately
20 microg/ml) gur (suppressed to 4-52% of control: gur-sensitive fibers),
whereas the remaining 14 fibers showed no such gur inhibition (77-106% of
control: gur-insensitive fibers). In gur-sensitive fibers, responses to sucrose
inhibited by gur recovered to approximately 70% of control responses after
rinsing the tongue with 15 mM beta-cyclodextrin and were almost abolished by
further treatment with 2% pronase. In gur-insensitive fibers, sucrose responses
were not inhibited by gur, but were largely suppressed by pronase. These results
suggest existence of two different receptor components for sweeteners with
different susceptibilities to gur in mouse taste cells, one gur sensitive and
the other gur insensitive. Taste cells possessing each component may be
specifically innervated by a particular type of chorda tympani neurons.

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

PMID: 10368423 [PubMed - indexed for MEDLINE]

45: J Nutr. 1999 Jun;129(6):1214-22.

Fecal steroid excretion is increased in rats by oral administration of gymnemic
acids contained in Gymnema sylvestre leaves.

Nakamura Y, Tsumura Y, Tonogai Y, Shibata T.

Division of Food Chemistry, National Institute of Health Sciences, Osaka Branch,
1-1-43, Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.

Gymnemic acids are the saponins with a triterpenoid structure contained in
Gymnema sylvestre leaves and have the hypoglycemic effects. In spite of the
cholesterol-binding properties of saponins, the effect of gymnemic acids on
cholesterol metabolism has not been elucidated to date. We investigated the
effects of gymnemic acids on fecal steroid excretion in rats. Three kinds of
extracts from Gymnema sylvestre leaves, extract (GSE), acid precipitate (GSA)
and column fractionate (GSF), of which the gymnemagenin (an aglycone of gymnemic
acids) concentrations are 58.87, 161.6, and 363.3 mg/g respectively, were used
for the experiments. These were administered to rats orally at the dose of
0.05-1.0 g/kg for 22 d. Rats were given free access to water and nonpurified
diet without cholesterol, and the differences in fecal excretion of steroids and
gymnemic acids were investigated. Although there were no significant effects of
GSE, GSA and GSF decreased body weight gain and food intakes in a dose-dependent
manner (P < 0.01). GSF (1.0 g/kg) significantly increased fecal excretion of
neutral steroids and bile acids in a dose-dependent manner (P < 0.05),
especially those of cholesterol and cholic acid (CA)-derived bile acids. The
increases in fecal steroid excretion of cholesterol, total neutral steroids,
total bile acids and CA-related bile acids were acute and significantly
correlated with fecal gymnemagenin levels (r2 = 0.2316-0.9861, P < 0. 05). These
results demonstrated for the first time that a high dose of gymnemic acids
increases fecal cholesterol and CA-derived bile acid excretion. Further studies
are needed to clarify the effect of gymnemic acids on cholesterol metabolism.

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

PMID: 10356090 [PubMed - indexed for MEDLINE]

46: Can J Physiol Pharmacol. 1998 Oct-Nov;76(10-11):1017-23.

Inhibitory effect of gymnemic acid on intestinal absorption of oleic acid in

Wang LF, Luo H, Miyoshi M, Imoto T, Hiji Y, Sasaki T.

Third Department of Internal Medicine, Faculty of Medicine, Tottori University,
Yonago, Japan.

Gymnemic acid, a mixture of triterpene glycosides extracted from the leaves of
Gymnema sylvestre, is known to inhibit the intestinal absorption of glucose in
human and rats. This work examined the effect of gymnemic acid on oleic acid
absorption by the method of intestinal perfusion in rats. The results showed the
following. (i) Gymnemic acid potently inhibited the absorption of oleic acid in
intestine. (ii) This inhibition was dose dependent and reversible. (iii) The
extent of inhibition and the recovery progress were extremely similar to that of
glucose absorption. (iv) Taurocholate did not affect the inhibitory effect of
gymnemic acid on oleic acid absorption, but lowering its concentration
facilitated the recovery from the inhibition. (v) The absorption of oleic acid
was not affected by other glycosides such as phloridzin, stevioside, and
glycyrrhizin. These new findings are important for understanding the roles of
gymnemic acid in therapy of diabetes mellitus and obesity.

Publication Types:
Comparative Study

PMID: 10100884 [PubMed - indexed for MEDLINE]

47: Altern Med Rev. 1999 Feb;4(1):46-7.

Gymnema sylvestre.

[No authors listed]

PMID: 9988783 [PubMed - indexed for MEDLINE]

48: J Biomol NMR. 1998 Nov;12(4):535-41.

High pressure NMR study of a small protein, gurmarin.

Inoue K, Yamada H, Imoto T, Akasaka K.

Division of Molecular Science, Graduate School of Science and Technology, Kobe
University, Japan.

The effect of pressure on the structure of gurmarin, a globular, 35-residue
protein from Gymnema sylvestre, was studied in aqueous environment (95% 1H2O/5%
2H2O, pH 2.0) with an on-line variable pressure NMR system operating at 750 MHz.
Two-dimensional TOCSY and NOESY spectra were measured as functions of pressure
between 1 and 2000 bar at 40 degrees C. Practically all the proton signals of
gurmarin underwent some shifts with pressure, showing that the entire protein
structure responds to, and is altered by, pressure. Most amide protons showed
different degrees of low field shifts with pressure, namely 0-0.2 ppm with an
average of 0.051 ppm at 2000 bar, showing that they are involved in hydrogen
bonding and that these hydrogen bonds are shortened by pressure by different
degrees. The tendency was also confirmed that the chemical shifts of the amide
protons exposed to the solvent (water) are more sensitive to pressure than those
internally hydrogen bonded with carbonyls. The pressure-induced shifts of the H
alpha signals of the residues in the beta-sheet showed a negative correlation
with the 'folding' shifts (difference between the shift at 1 bar and that of a
random coil), suggesting that the main-chain torsion angles of the beta-sheet
are slightly altered by pressure. Significant pressure-induced shifts were also
observed for the side-chain protons (but no larger than 10% of the 'folding'
shifts), demonstrating that the tertiary structure of gurmarin is also affected
by pressure. Finally, the linearity of the pressure-induced shifts suggest that
the compressibility of gurmarin is invariant in the pressure range between 1 and
2000 bar.

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

PMID: 9862129 [PubMed - indexed for MEDLINE]

49: Gen Pharmacol. 1998 Sep;31(3):495-6.

Possible mechanism of antihyperglycemic effect of Gymnema sylvestre leaf
extract, part I.

Chattopadhyay RR.

Indian Statistical Institute, Calcutta.

1. Effect of water soluble fraction of alcoholic extract of G. sylvestre leaves
on glycogen content by isolated rat hemidiaphragm was studied in normal and
glucose fed hyperglycemic rats. 2. The leaf extract by itself failed to alter
the hepatic glycogen content in normal rats. 3. In glucose fed rats, the leaf
extract lowered the glycogen content of the tissue significantly (P<0.05) and
this was further lowered when both exogenous insulin and leaf extract was
administered. 4. The results are discussed.

PMID: 9703226 [PubMed - indexed for MEDLINE]

50: Chem Senses. 1998 Jun;23(3):303-7.

Reduction of the suppressive effects of gurmarin on sweet taste responses by
addition of beta-cyclodextrin.

Ninomiya Y, Inoue M, Imoto T.

Department of Oral Physiology, Asahi University School of Dentistry, Gifu,
Japan. [email protected]

Cyclodextrins (CDs) have the remarkable ability to form inclusion complexes with
a wide variety of guest molecules. In the present study, possible influences of
CDs on gurmarin inhibition of the chorda tympani responses to sucrose were
examined in C57BL mice. Responses to sucrose were suppressed to approximately
50% of control by treatment of the tongue with 30 micrograms/ml (approximately
7.1 microM) gurmarin. Rinsing the tongue with 15 mM beta-CD after gurmarin gave
rapid recovery of the suppressed sucrose responses to approximately 85% of
control, whereas 15 mM alpha- or gamma-CD did not. When gurmarin was mixed with
beta-CD, the suppressive effects of gurmarin on sucrose responses were largely
reduced. No such reduction was observed for mixtures with alpha- and gamma-CD.
Gurmarin includes tyrosine and tryptophan residues whose aromatic rings are
directed outward and can probably form inclusion complexes with beta-CD.
Therefore, the observed reduction of the effects of gurmarin may be due to
steric hindrances in inclusion complexes of gurmarin with beta-CD that may
interfere with gurmarin binding to sweet taste receptors.

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

PMID: 9669043 [PubMed - indexed for MEDLINE]

51: Biopolymers. 1998 Aug;46(2):65-73.

Synthesis, characterization, and sweetness-suppressing activities of gurmarin
analogues missing one disulfide bond.

Ota M, Shimizu Y, Tonosaki K, Ariyoshi Y.

Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.

The sweetness-suppressing polypeptide gurmarin isolated from Gymnema sylvestre
consists of 35 amino acid residues and includes three intramolecular disulfide
bonds. The roles of the three disulfide bonds were investigated by replacing
each with two alanine residues by solid-phase synthesis. Nine analogues of
[Ala3,18]gurmarin, [Ala10,23]gurmarin, and [Ala17,33]-gurmarin were obtained.
Three analogues had native disulfide bonds, while the other six had non-native
disulfide bonds. The three analogues with native disulfide bonds suppressed the
response to sucrose, but not those to glucose, fructose, saccharin, or glycine
in rats. In contrast, the six analogues with non-native disulfide bonds did not
suppress the responses to any of these sweeteners. These results suggest that
the native disulfide bonds of gurmarin are necessary for interaction with the
receptor protein, and that the sucrose-specific receptor site is present in

PMID: 9664842 [PubMed - indexed for MEDLINE]

52: Am J Physiol. 1998 May;274(5 Pt 2):R1324-30.

Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the
diabetic db/db mouse.

Ninomiya Y, Imoto T, Yatabe A, Kawamura S, Nakashima K, Katsukawa H.

Department of Oral Physiology, Chemistry and Pediatric Dentistry, Asahi
University School of Dentistry, Gifu, Japan.

Genetically diabetic db/db mice show greater neural and behavioral responses to
sugars than lean control mice. The present study examined chorda tympani
responses of db/db mice to nonsugar sweeteners and their inhibition by a sweet
response inhibitor, gurmarin. The results showed that responses to sucrose,
saccharin, glycine, L-alanine, and D-tryptophan, but not to D-phenylalanine,
were approximately 1.5 times greater in db/db mice than in control mice.
Treatment of the tongue with gurmarin suppressed responses to these sweeteners
in db/db and control mice, but the extent of suppression was considerably
smaller in db/db mice. The magnitudes of gurmarin-sensitive components of the
response to sweeteners in db/db mice were not significantly different from those
in control mice, whereas the magnitudes of gurmarin-insensitive components in
db/db mice were about twice as large as those in control mice. These results
suggest that the enhancement of chorda tympani responses in db/db mice to
sucrose and other nonsugar sweeteners may occur through gurmarin-insensitive
membrane components.

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

PMID: 9644046 [PubMed - indexed for MEDLINE]

53: Appl Human Sci. 1998 Jan;17(1):9-17.

Influence of sweet suppressing agent on gustatory brain evoked potentials
generated by taste stimuli.

Min BC, Sakamoto K.

Department of Communications and Systems, University of Electro-Communications,
Tokyo, Japan.

A measurement system was employed to detect gustatory evoked potentials from
human scalp by stimulus of a taste solution with the use of a laser beam device.
The evoked potentials for four taste qualities (i.e., sweet-sucrose,
salty-sodium chloride, sour-tartaric acid, and bitter-quinine-HCl) were measured
before and after treatment with a sweet suppressing agent (i.e., gymnema
sylvestre extract) to the tongue of a human. The solution was given to the
chorda tympani nerve located 20 mm from the apex of the tongue and 15 mm from
the left side of the center line. The maximum potential level and its latency
were evaluated. Artificial saliva was used as a control solution. The evoked
potentials obtained were averaged by eight evoked potentials to detect the peak
of the evoked potential more clearly. The latencies for taste stimuli were found
on two kinds of peaks at approximately 50 ms and 180 ms. These peaks are P1 and
P2. The purpose of this study is to investigate the influence of sweet
suppressing agent on P1 and P2. The influence of the sweet suppressing agent to
evoked potential by salty, sour, and bitter taste stimuli was not recognized,
but the responses to sweet (sucrose) were abolished after treatment with a sweet
suppressing agent. It was recognized that the peak P2 originated from the taste
stimulus. The peak P1 did not suffer the influence of the sweet suppression, so
it was considered that the response to P1 was due to sensations other than the
gustatory response, such as somatosense.

PMID: 9575639 [PubMed - indexed for MEDLINE]

54: J Am Coll Nutr. 1998 Apr;17(2):116-23.

Comparative effects of chromium, vanadium and gymnema sylvestre on sugar-induced
blood pressure elevations in SHR.

Preuss HG, Jarrell ST, Scheckenbach R, Lieberman S, Anderson RA.

Department of Medicine, Georgetown University Medical Center, Washington, DC
20007, USA.

OBJECTIVE: Effects on systolic blood pressure (SBP) of ingesting three agents
reported to influence insulin metabolism, i.e., chromium polynicotinate,
bis(maltolato)oxovanadium (BMOV), and the herb, Gymnema sylvestre, were assessed
simultaneously in spontaneously hypertensive rats (SHR). METHODS: In the first
study, SHR were fed either a starch, sugar, or sugar diet containing chromium
polynicotinate, bis(maltolato)oxovanadium (BMOV), or G. sylvestre. Tail SBP was
estimated indirectly and various blood chemistries were measured. TBARS
formation was determined in hepatic and renal tissue. In a second study, tail
SBP was measured in SHR ingesting diets containing different concentrations of
BMOV. RESULTS: Compared to starch, SHR consuming sucrose showed a significant
elevation of SBP within days that was maintained for the duration of study.
Addition of chromium polynicotinate to the sucrose diet at the beginning of
study prevented the sucrose-induced elevation of SBP for 2 weeks, but SBP rose
significantly after that. BMOV at high concentrations overcame the
sucrose-induced rise in SBP and even decreased SBP below values seen in SHR
eating the starch diet, but marked weight loss was noted. A second study
examined different concentrations of BMOV. At 0.01% w/w concentration of BMOV,
SBP was still significantly decreased, even though SHR did not lose body weight
(BW) early on. SHR consuming G. sylvestre showed no change or even elevated SBP.
Hepatic thiobarbituric acid reacting substances (TBARS) formation, an estimate
of lipid peroxidation, was decreased by chromium polynicotinate and BMOV, and
renal TBARS by chromium polynicotinate. Circulating cholesterol concentrations
were decreased in the SHR consuming G. sylvestre. CONCLUSIONS: Chromium
decreases the portion of SBP elevated by high sucrose intake as shown
previously, but high levels of sucrose ingestion can eventually overcome this.
BMOV overcame sucrose-induced elevation of SBP as well as some of the "genetic
hypertension." Different from chromium, this decrease was not overcome by high
levels of dietary sucrose. The significant lowering of cholesterol with G.
sylvestre ingestion indicates some effect on metabolism, but G. sylvestre did
not lower and even raised SBP.

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

PMID: 9550454 [PubMed - indexed for MEDLINE]

55: Structure. 1997 Nov 15;5(11):1525-35.

The structure of versutoxin (delta-atracotoxin-Hv1) provides insights into the
binding of site 3 neurotoxins to the voltage-gated sodium channel.

Fletcher JI, Chapman BE, Mackay JP, Howden ME, King GF.

Department of Biochemistry University of Sydney Sydney, NSW 2006, Australia.

BACKGROUND: Versutoxin (delta-ACTX-Hv1) is the major component of the venom of
the Australian Blue Mountains funnel web spider, Hadronyche versuta.
delta-ACTX-Hv1 produces potentially fatal neurotoxic symptoms in primates by
slowing the inactivation of voltage-gated sodium channels; delta-ACTX-Hv1 is
therefore a useful tool for studying sodium channel function. We have determined
the three-dimensional structure of delta-ACTX-Hv1 as the first step towards
understanding the molecular basis of its interaction with these channels.
RESULTS: The solution structure of delta-ACTX-Hv1, determined using NMR
spectroscopy, comprises a core beta region containing a triple-stranded
antiparallel beta sheet, a thumb-like extension protruding from the beta region
and a C-terminal 310 helix that is appended to the beta domain by virtue of a
disulphide bond. The beta region contains a cystine knot motif similar to that
seen in other neurotoxic polypeptides. The structure shows homology with
mu-agatoxin-I, a spider toxin that also modifies the inactivation kinetics of
vertebrate voltage-gated sodium channels. More surprisingly, delta-ACTX-Hv1
shows both sequence and structural homology with gurmarin, a plant polypeptide.
This similarity leads us to suggest that the sweet-taste suppression elicited by
gurmarin may result from an interaction with one of the downstream ion channels
involved in sweet-taste transduction. CONCLUSIONS: delta-ACTX-Hv1 shows no
structural homology with either sea anemone or alpha-scorpion toxins, both of
which also modify the inactivation kinetics of voltage-gated sodium channels by
interacting with channel recognition site 3. However, we have shown that
delta-ACTX-Hv1 contains charged residues that are topologically related to those
implicated in the binding of sea anemone and alpha-scorpion toxins to mammalian
voltage-gated sodium channels, suggesting similarities in their mode of
interaction with these channels.

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

PMID: 9384567 [PubMed - indexed for MEDLINE]

56: Biopolymers. 1998 Mar;45(3):231-8.

Role of hydrophobic amino acids in gurmarin, a sweetness-suppressing

Ota M, Shimizu Y, Tonosaki K, Ariyoshi Y.

Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.

The sweetness-suppressing polypeptide gurmarin isolated from Gymnema sylvestre
consists of 35 amino acid residues and contains three intramolecular disulfide
bonds. Nuclear magnetic resonance analysis showed that the hydrophobic side
chains of Tyr-13, Tyr-14, Trp-28, and Trp-29 in gurmarin are oriented outwardly.
Together with the hydrophobic side chains of Leu-9, Ile-11, and Pro-12, they
form a hydrophobic cluster, and therefore these hydrophobic groups are assumed
to act as the site for interaction with the receptor protein. To examine the
roles of these hydrophobic amino acids, they were replaced by Gly. The resulting
[Gly13,14,28,29] gurmarin and [Gly9,11,13,14,28,29]-gurmarin did not suppress
the responses to sucrose, glucose, fructose, or Gly. This result strongly
suggests that these hydrophobic amino acids are involved in the interaction with
the receptor protein.

PMID: 9465786 [PubMed - indexed for MEDLINE]

57: Chem Pharm Bull (Tokyo). 1997 Dec;45(12):2034-8.

Medicinal foodstuffs. X. Structures of new triterpene glycosides,
gymnemosides-c, -d, -e, and -f, from the leaves of Gymnema sylvestre R. Br.:
influence of gymnema glycosides on glucose uptake in rat small intestinal

Yoshikawa M, Murakami T, Matsuda H.

Kyoto Pharmaceutical University, Japan.

Following the characterization of gymnemosides-a and -b, new triterpene
glycosides, gymnemosides-c, -d, -e, and -f, were isolated from the leaves of
Gymnema (G.) sylvestre R. BR. Their chemical structures were elucidated on the
basis of chemical and physicochemical evidence as follows:
21-O-benzoyl-28-O-acetylgymnemagenin 3-O-beta-D-glucopyranosiduronic acid
(gymnemoside-c), 23-O-[beta-D-xylopyranosyl (1-->6)-beta-D-glucopyranosyl
(1-->6)-beta-D-glucopyranosyl] gymnestrogenin (gymnemoside-d),
23-O-[beta-D-xylopyranosyl (1-->6)-beta-D-glucopyranosyl (1-->6)-beta-D-
glucopyranosyl]-28-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl]
23-hydroxylongispinogenin (gymnemoside-e), 23-O-[beta-D-xylopyranosyl
(1-->6)-beta-D-glucopyranosyl] 3 beta,16 beta,23,28-tetrahydroxyolean-18-ene
(gymnemoside-f). The inhibitory effects of gymnemosides-c, -d, -e, and -f and
principal triterpene glycosides from G. sylvestre on glucose uptake in rat small
intestinal fragments were examined, and gymnemic acids II, III, and IV,
gymnemasaponin V, and gymnemoside-f were found to exhibit the inhibitory

Publication Types:
In Vitro

PMID: 9433774 [PubMed - indexed for MEDLINE]

58: Chem Pharm Bull (Tokyo). 1997 Oct;45(10):1671-6.

Medicinal foodstuffs. IX. The inhibitors of glucose absorption from the leaves
of Gymnema sylvestre R. BR. (Asclepiadaceae): structures of gymnemosides a and

Yoshikawa M, Murakami T, Kadoya M, Li Y, Murakami N, Yamahara J, Matsuda H.

Kyoto Pharmaceutical University, Japan.

Although the glycosidic fraction from the dried leaves of Gymnema sylvestre R.
BR., gymnemic acid, was reported to be effective for diabetes, it showed little
inhibitory activity on the increase of serum glucose level in oral
glucose-loaded rats. From the glycosidic fraction, six triterpene glycosides,
gymnemosides a, b, c, d, e, and f, were isolated together with nine known
triterpene glycosides. The structures of gymnemosides a and b were determined on
the basis of chemical and physicochemical evidence as
21-O-tigloyl-22-O-acetylgymnemagenin 3-O-beta-D-glucopyranosiduronic acid and
16-O-acetyl-21-O-tigloylgymnemagenin 3-O-beta-D-glucopyranosiduronic acid,
respectively. In addition, an acetyl group linked to the 16- or 22-hydroxyl
group in gymnemosides a and b was found to migrate easily to the primary
28-hydroxyl group, while the acyl migration from the 28-position was rarely
observed. The inhibitory activity of each triterpene glycoside from gymnemic
acid was examined to determine its impact on the increase of serum glucose level
in oral glucose-loaded rats. Gymnemoside b and gymnemic acids III, V, and VII
were found to exhibit a little inhibitory activity against glucose absorption,
but the principal constituents, gymnemic acid I and gymnemasaponin V, lacked
this activity.

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

PMID: 9353896 [PubMed - indexed for MEDLINE]

59: J Vet Med Sci. 1997 Sep;59(9):753-7.

Suppression of glucose absorption by extracts from the leaves of Gymnema

Shimizu K, Ozeki M, Tanaka K, Itoh K, Nakajyo S, Urakawa N, Atsuchi M.

Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science
University, Tokyo, Japan.

Gymnema sylvestre (GS) is one of the Asclepiad strains that grows in South-east
Asia. Their therapeutic effects for treating diabetes mellitus, rheumatic
arthritis and gout have been well known for a long time. However, the problem is
that GS suppresses sweetness and tastes bitter. For this study, we chose Gymnema
inodorum (GI) instead of GS, since it has an advantage that it does not suppress
sweetness nor is it bitter in taste. In this paper, effects of glucose
availability of some saponin fractions (F-I to F-IV) extracted from GI leaves,
which were obtained by high-performance liquid chromatography were studied on a
high K(+)-induced contraction of guinea-pig intestinal smooth muscle, O2
consumption on guinea-pig ileum, glucose-evoked transmural potential difference
(delta PD) of guinea-pig everted intestine and blood glucose level in glucose
tolerance tests on rats. The extracts of GI leaves suppressed the intestinal
smooth muscle contraction, decreased the O2 consumption, inhibited the glucose
evoked-transmural potential, and prevented the blood glucose level. Our studies
suggest that the component of GI inhibits the increase in the blood glucose
level by interfering with the intestinal glucose absorption process.

PMID: 9342697 [PubMed - indexed for MEDLINE]

60: J Vet Med Sci. 1997 Apr;59(4):245-51.

Suppression of glucose absorption by some fractions extracted from Gymnema
sylvestre leaves.

Shimizu K, Iino A, Nakajima J, Tanaka K, Nakajyo S, Urakawa N, Atsuchi M, Wada
T, Yamashita C.

Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science
University, Tokyo, Japan.

Extracts containing gymnemic acids, which were extracted from the leaves of
Gymnema sylvestre (GS) as nine fractions, were evaluated for their effects on a
high K(+)-induced contraction of guinea-pig ileal longitudinal muscles, on
glucose transport mediated by the difference of glucose-evoked transmural
potential difference (delta PD) in the inverted intestine of guinea-pig and rat,
and on blood glucose in rat. Among nine fractions obtained by high performance
liquid chromatography from the extract, f-2 and f-4 strongly suppressed the high
K(+)-induced contraction of the ileal muscle, f-3 and f-5 did so moderately, and
f-8 and f-9 did so weakly, whereas the other fractions did not affect it. The
degree of suppression of high K(+)-induced contraction by f-2 at 74% was almost
the same as that of f-4 at 67%, at concentrations of 0.1 mg/ml. The suppressed
contraction by f-2 or f-4 was recovered by adding 5.5 mM pyruvate. The delta PD
increased by 5.5 mM glucose in the inverted intestines of guinea-pig and rat
were equally suppressed by 0.1 mg/ml of f-2 or f-4 to 40%. In a rat sucrose
tolerance test, f-2 and f-4 suppressed the elevation of blood glucose level.
Both f-2 and f-4 suppressed the contraction of guinea-pig ileal longitudinal
muscle, interfered with the increase in delta PD induced by glucose in the
inverted intestines of guinea-pig and rat, and inhibited the elevation of blood
glucose level. In conclusion, it is suggested that some of the extracts
containing gymnemic acids from GS leaves suppress the elevation of blood glucose
level by inhibiting glucose uptake in the intestine.

PMID: 9152931 [PubMed - indexed for MEDLINE]

61: Chem Senses. 1997 Apr;22(2):163-9.

Changes in outward K+ currents in response to two types of sweeteners in sweet
taste transduction of gerbil taste cells.

Uchida Y, Sato T.

Department of Physiology, Nagasaki University School of Dentistry, Japan.

Using the whole cell patch clamp technique, we measured changes in outward K+
currents of gerbil taste cells in response to different kinds of sweeteners.
Outward K+ currents of the taste cell induced by depolarizing pulses were
suppressed by sweet stimuli such as 10 mM Na-saccharin. The membrane-permeable
analog of cAMP, cpt-cAMP, also decreased outward K+ currents. On the other hand,
the K+ currents were enhanced by amino acid sweeteners such as 10 mM
D-tryptophan. The outward K+ current was enhanced by external application of
Ca(2+)-transporting ionophore, 5 microM ionomycin, and intracellular application
of 5 microM inositol-1,4,5-trisphosphate (IP3). The outward K+ currents were no
longer suppressed by 10 mM Na-saccharin containing 20 microM gurmarin, but were
still enhanced by 10 mM D-tryptophan containing 20 microM gurmarin. These
results suggest that sweet taste transduction for one group of sweeteners such
as Na-saccharin in gerbils is concerned with an increase of the intracellular
cAMP level, and that the transduction for the other group of sweeteners such as
D-tryptophan is concerned with an increase of the intracellular IP3 level which
releases Ca2+ from the internal stores.

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

PMID: 9146906 [PubMed - indexed for MEDLINE]

62: Am J Physiol. 1997 Mar;272(3 Pt 2):R1002-6.

Lack of gurmarin sensitivity of sweet taste receptors innervated by the
glossopharyngeal nerve in C57BL mice.

Ninomiya Y, Inoue M, Imoto T, Nakashima K.

Department of Oral Physiology and Chemistry, Asahi University School of
Dentistry, Hozumi, Motosu, Japan.

Effects of a sweet response inhibitor, gurmarin, on responses of the chorda
tympani and glossopharyngeal nerves were studied in the C57BL/KsJ strain of
mice. The lingual application of gurmarin at 3.0 microg/ml (approxiamtely 0.7
microM) or more significantly suppressed chorda tympani responses to 0.5 M
sucrose, as previously reported. The magnitude of gurmarin inhibition of the
chorda tympani responses reached a plateau (approximately 45% of control) at 50
microg/ml (approximately 11.9 microM). In contrast, no such gurmarin inhibition
of sucrose responses was observed in the glossopharyngeal nerve even at 100
microg/ml (approximately 23.8 microM). The lingual application of a proteolytic
enzyme, pronase, suppressed sucrose responses to <20% of control in both chorda
tympani and glossopharyngeal nerves. These results suggest differential
sensitivity to gurmarin by sweet taste receptors innervated by the chorda
tympani and the glossopharyngeal nerves. The former apparently possess gurmarin
sensitivity, whereas most of the latter may be lacking sensitivity.

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

PMID: 9087667 [PubMed - indexed for MEDLINE]

63: J Smooth Muscle Res. 1996 Oct;32(5):219-28.

[Inhibitory effects of glucose utilization by gymnema acids in the guinea-pig
ileal longitudinal muscle]

[Article in Japanese]

Shimizu K, Abe T, Nakajyo S, Urakawa N, Atsuchi M, Yamashita C.

Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science
University, Tokyo, Japan.

Two substances identified as ((3 beta, 4 alpha, 16 beta, 21 beta, 22
alpha)-21-tigloxy-16, 22, 23, 28-tetrahydroxyolean-12-en-3-yl-beta
D-glucopyranosiduronic acid) (GA1) and ((3 beta, 4 alpha, 16 beta, 21 beta, 22
alpha)-21-(2-methylbutyroxy)-16, 22, 23,
28-tetrahydroxyolean-12-en-3-yl-beta-D-glucopyranosiduronic acid) (GA2)
identified among the gymnemic acids are triterpene glycosides extracted from
Gymnema sylvestre leaves. We examined the effects of GA1 or GA2 on high
K(+)-induced contraction in the guinea-pig longitudinal muscle. A sustained
muscle contraction induced by hyperosmotically added 65.4 mM KCI (H-65K+) was
suppressed by GA1 or GA2 (7.7 x 10(-5) M). Simultaneous measurements of reduced
pyridine nucleotide (PNred) or oxidized flavin protein (FPox) by the
fluorescence technique and of contractile force revealed that GA1 and GA2
reduced the increase of PNred fluorescence and contractile force induced by
H-65K+, whereas FPox fluorescence induced by it further increased. Reduced
muscle contraction induced by GA1 or GA2 was restored by 5.5 mM pyruvate.
Simultaneous measurements of intracellular Ca2+ [Ca2+]1 level and contractile
force indicated that [Ca2+]1 level, which increased by H-65K+, hardly changed
with GA1 and GA2. In summary, both GA1 and GA2, which are among the gymnemic
acids, suppressed high K(+)-induced contraction in the guinea-pig ileal
longitudinal muscle. The difference between these two gymnemic acids was not
significant. The inhibitory effect of GA1 and GA2 on smooth muscle were assumed
to be a result of inhibiting glucose uptake, which is an energy source of the
muscle, whereas the inhibitory mechanisms were probably not mediated by Ca2+.

Publication Types:
English Abstract

PMID: 8985922 [PubMed - indexed for MEDLINE]

64: Biopolymers. 1996 Aug;39(2):199-205.

Synthesis and characterization of the sweetness-suppressing polypeptide gurmarin
and ent-gurmarin.

Ota M, Tonosaki K, Miwa K, Fukuwatari T, Ariyoshi Y.

Central Research Laboratories, Ajinomoto Co., Inc. Kawasaki, Japan.

The sweetness-suppressing polypeptide gurmarin isolated from the leaves of
Gymnema sylvestre consists of 35 amino acid residues including three
intramolecular disulfide bonds. Herein, the total chemical synthesis of gurmarin
was performed by the stepwise fluoren-9-ylmethoxy-carbonyl solid-phase method,
the yield of reduced gurmarin being 1.9% based on the starting amino acid resin.
Disulfide formation was carried out in the presence of a redox system of reduced
glutathione/oxidized glutathione to give gurmarin in a yield of 35.5%. The
product was identical to natural gurmarin by analytical reverse phase high
performance liquid chromatography (RP-HPLC), mass spectroscopy (MS), and peptide
mapping, and suppressed the responses to sucrose, D-glucose, and L-glucose in a
rat. The D enantiomer (all D-amino acid gurmarin) was also synthesized, and was
shown to be the mirror image of gurmarin. Interestingly, the D enantiomer
(ent-gurmarin) also suppressed the responses to sucrose, D-glucose, and
L-glucose in a rat.

PMID: 8679949 [PubMed - indexed for MEDLINE]

65: Phytochemistry. 1996 Mar;41(4):1181-5.

Triterpenoid saponins from Gymnema sylvestre.

Sahu NP, Mahato SB, Sarkar SK, Poddar G.

Indian Institute of Chemical Biology, Calcutta, India.

Besides six known gymnemic acids, four new tritepenoid saponins, gymnemasins A,
B, C and D, isolated from the leaves of Gymnema sylvestre, were identified as
3-O-[beta-D-glucopyranosyl(1-->3)-beta-D-glucuronopyranosyl]-22-O- tigloyl-
gymnemanol, 3-O-[beta-D-glucopyranosyl
3-O-beta-D-glucuronopyranosyl-22-O-tigloyl-gymnemanol and
3-O-beta-D-glucuronopyranosyl-gymnemanol, respectively. The aglycone,
gymnemanol, which is a new compound, was characterized as 3 beta, 16 beta, 22
alpha, 23, 28-pentahydroxyolean-12-ene.

PMID: 8728717 [PubMed - indexed for MEDLINE]

66: Chem Pharm Bull (Tokyo). 1996 Feb;44(2):469-71.

New hypoglycemic constituents in "gymnemic acid" from Gymnema sylvestre.

Murakami N, Murakami T, Kadoya M, Matsuda H, Yamahara J, Yoshikawa M.

Kyoto Pharmaceutical University, Japan.

Investigation of hypoglycemic activity of major saponin constituents from
"gymnemic acid", a crude saponin fraction of G. sylvestre, exposed not only two
new saponins, gymnemosides a (1) and b (2), but also gymnemoside b and gymnemic
acid V (7) as active principles. Furthermore, an acetyl group linked 16- or
22-hydroxy group in 1 and 2 was found to migrate easily to primary 28-hydroxyl
group, while acyl migration from 28-hydroxy group in 3 was little observed.

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

PMID: 8998848 [PubMed - indexed for MEDLINE]

67: Biosci Biotechnol Biochem. 1995 Oct;59(10):1956-7.

Location of the disulfide bonds of the sweetness-suppressing polypeptide

Ota M, Ariyoshi Y.

Central Research Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.

The sweetness-suppressing polypeptide gurmarin has been isolated from the leaves
of Gymnema sylvestre and consists of 35 amino acid residues including three
intramolecular disulfide bonds. The primary structure has already been
determined. The positions of the disulfide bonds were located, by a combination
of mass spectrometric analysis and sequencing of cystine-containing peptides
obtained by thermolysin-catalyzed hydrolysis of gurmarin, to be at Cys3-Cys18,
Cys10-Cys23, and Cys17-Cys33.

PMID: 8534991 [PubMed - indexed for MEDLINE]

68: Diabetes Res Clin Pract. 1995 Jul;29(1):11-7.

Effects of seishin-renshi-in and Gymnema sylvestre on insulin resistance in
streptozotocin-induced diabetic rats.

Tominaga M, Kimura M, Sugiyama K, Abe T, Igarashi K, Igarashi M, Eguchi H,
Sekikawa A, Ogawa A, Manaka H, et al.

Third Department of Internal Medicine, Yamagata University School of Medicine,

Although there is no concept of insulin resistance in traditional Kampo
(Chinese) medicine and Indian medicine, we had the hypothesis that some drug in
a mixture of crude drugs which was believed to ameliorate diabetes mellitus may
have had the effect of improving insulin resistance. To test this hypothesis,
the effects of Seishin-renshi-in (Chinese medicine) and Gymnema sylvestre
(Indian medicine) on the insulin resistance of streptozotocin-induced diabetic
rats was studied by the glucose clamp technique. Oral administration of
Seishin-renshi-in (800 mg/kg/day) with injections of a minimum dose of
Ultralente insulin decreased urine volume and urinary glucose excretion during a
7-day treatment period and improved the insulin stimulated glucose uptake in
peripheral tissues, as well as improving the insulin suppressed hepatic glucose
output during glucose clamp. However, G. sylvestre (120 mg/kg/day) treatment did
not improve insulin resistance. We conclude that Seishin-renshi-in, with a small
dose of insulin, improved insulin resistance in streptozotocin-induced diabetic
rats, but Gymnema sylvestre did not.

PMID: 8593754 [PubMed - indexed for MEDLINE]

69: J Ethnopharmacol. 1995 Jun 23;47(1):9-26.

Plant-derived triterpenoid sweetness inhibitors.

Suttisri R, Lee IS, Kinghorn AD.

Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy,
University of Illinois at Chicago 60612, USA.

Considerable recent attention has been focused on naturally occurring compounds
with taste-modifying activity, which are of potential use in both dietary
sweetness management and in gaining a better understanding of the sweet taste
sensation. This review summarizes information on the phytochemistry and
biological activity of more than 40 triterpenoid sweetness inhibitors that have
been isolated from the leaves of three medicinal plants, namely, Gymnema
sylvestre R.Br. (Asclepiadaceae), Ziziphus jujuba P. Miller (Rhamnaceae), and
Hovenia dulcis Thunb. (Rhamnaceae).

Publication Types:

PMID: 7564423 [PubMed - indexed for MEDLINE]

70: Brain Res. 1995 Apr 3;676(1):63-8.

Electrophysiological characterization of the inhibitory effect of a novel
peptide gurmarin on the sweet taste response in rats.

Miyasaka A, Imoto T.

Department of Physiology, Faculty of Medicine, Tottori University, Yonago,

The effect of an anti-sweet peptide, gurmarin purified from the leaves of
Gymnema sylvestre, was studied electrophysiologically on taste responses of the
rat chorda tympani. The action of gurmarin was highly specific to sweet taste so
that responses to various sweeteners including sugars, sweet amino acids and an
artificial sweetener, saccharin were all suppressed. The most effective pH at
which the rat tongue was treated with gurmarin was found to be 4.5, which
corresponds to the isoelectric point of the peptide. At this condition about 5
microM of gurmarin was sufficient to reveal maximal effect and this was still
significant at 0.5 microM (2 micrograms/ml). Although the suppressed responses
required several hours to attain complete recovery, anti-gurmarin serum
shortened the recovery time considerably. On the other hand, intravenous
injection of gurmarin did not cause any significant effects on taste responses
at all. These results suggest that gurmarin acts on the apical side of the taste
cell, possibly by binding to the sweet taste receptor protein.

PMID: 7796179 [PubMed - indexed for MEDLINE]

71: J Biomol NMR. 1995 Apr;5(3):297-305.

Three-dimensional structure of gurmarin, a sweet taste-suppressing polypeptide.

Arai K, Ishima R, Morikawa S, Miyasaka A, Imoto T, Yoshimura S, Aimoto S,
Akasaka K.

Department of Chemistry, Faculty of Science, Kyoto University, Japan.

The solution structure of gurmarin was studied by two-dimensional proton NMR
spectroscopy at 600 MHz. Gurmarin, a 35-amino acid residue polypeptide recently
discovered in an Indian-originated tree Gymnema sylvestre, selectively
suppresses the neural responses of rat to sweet taste stimuli. Sequence-specific
resonance assignments were obtained for all backbone protons and for most of the
side-chain protons. The three-dimensional solution structure was determined by
simulated-annealing calculations on the basis of 135 interproton distance
constraints derived from NOEs, six distance constraints for three hydrogen bonds
and 16 dihedral angle constraints derived from coupling constants. A total of 10
structures folded into a well-defined structure with a triple-stranded
antiparallel beta-sheet. The average rmsd values between any two structures were
1.65 +/- 0.39 A for the backbone atoms (N, C alpha, C) and 2.95 +/- 0.27 A for
all heavy atoms. The positions of the three disulfide bridges, which could not
be determined chemically, were estimated to be Cys3-Cys18, Cys10-Cys23 and
Cys17-Cys33 on the basis of the NMR distance constraints. This disulfide bridge
pattern in gurmarin turned out to be analogous to that in omega-conotoxin and
Momordica charantia trypsin inhibitor-II, and the topology of folding was the
same as that in omega-conotoxin.

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

PMID: 7787425 [PubMed - indexed for MEDLINE]

72: Am J Physiol. 1995 Apr;268(4 Pt 2):R1019-25.

Gurmarin inhibition of sweet taste responses in mice.

Ninomiya Y, Imoto T.

Department of Oral Physiology, Asahi University School of Dentistry, Gifu,

The inhibitory effects of gurmarin (a peptide isolated from the leaves of
Gymnema sylvestre) on sweet taste responses were studied by examining the chorda
tympani nerve responses to various taste substances before and after lingual
treatment with gurmarin in C57BL and BALB mice. Treatment with gurmarin at 3
micrograms/ml or more selectively suppressed responses to sucrose without
affecting responses to NaCl, HCl, and quinine in C57BL mice, whereas gurmarin at
100 micrograms/ml did not significantly suppress sucrose responses in BALB mice.
Responses to various sweet substances in C57BL mice decreased to approximately
45-75% of control after gurmarin, and the suppressive effect of gurmarin was
reversible. The profile of the residual responses of C57BL mice to various
sweeteners after gurmarin was almost identical to that of BALB mice, which was
hardly affected by gurmarin. These results strongly suggest that there are at
least two types of sweet taste receptors in mice, gurmarin-sensitive and
-insensitive. Probably, C57BL and BALB mice share an identical
gurmarin-insensitive receptor, and C57BL mice also have a gurmarin-sensitive

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

PMID: 7733384 [PubMed - indexed for MEDLINE]

73: Arch Histol Cytol. 1994 Dec;57(5):531-4.

Histological localization of the sweet taste receptor in rat taste buds by the
use of gurmarin, a sweet taste-suppressing peptide.

Yoshie S, Miyasaka A, Imoto T.

Department of Oral Anatomy, Nippon Dental University School of Dentistry at
Niigata, Japan.

The binding site of gurmarin, a peptide inhibiting the sweet-taste sensation,
was studied in taste buds in rat circumvallate papillae by means of a
histochemical technique. Frozen sections of tongues were incubated with gurmarin
conjugated with biotin and thereafter examined with a light microscope. Positive
reactivity for the peptide was localized to the taste hairs, the apical
projections of taste bud cells. The reaction appeared in about 10% of the
circumvallate taste buds examined. As electrophysiological studies indicate that
gurmarin suppresses the sweet-taste sensation at the level of reception, the
present study suggests that the receptor for sweet taste is located on the taste
hairs, and, furthermore, is present only in a certain, limited number of the
taste buds.

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

PMID: 7734180 [PubMed - indexed for MEDLINE]

74: Physiol Behav. 1994 Oct;56(4):741-5.

Differences in taste responses to Polycose and common sugars in the rat as
revealed by behavioral and electrophysiological studies.

Sako N, Shimura T, Komure M, Mochizuki R, Matsuo R, Yamamoto T.

Department of Behavioral Physiology, Faculty of Human Sciences, Osaka
University, Japan.

Behavioral and electrophysiological experiments were performed to examine the
suggestion that rats have two types of carbohydrate taste receptors, one for
polysaccharides (e.g., Polycose) and one for common sugars (e.g., sucrose).
Qualitative difference between the tastes of Polycose and sugars including
sucrose, maltose, glucose, and fructose was surveyed by means of a conditioned
taste aversion paradigm in which the number of licks for 20 s to each taste
stimulus was measured. Aversive conditioning to Polycose did not generalize to
sugars, while aversive conditioning to sucrose generalized to other sugars, but
not to Polycose. In the electrophysiological study, taste responses of the whole
chorda tympani were recorded. A proteolytic enzyme, pronase E, suppressed nerve
responses to both Polycose and sugars to less than 50%. A novel anti-sweet
peptide, gurmarin, strongly suppressed responses to sugars, but had essentially
no effect on Polycose responses. On the other hand, KHCO3 enhanced responses to
sugars to about 300%, but had little effect on Polycose responses. These results
have confirmed the notion that rats can differentiate the tastes between
Polycose and common sugars and that rats have two types of carbohydrate

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

PMID: 7800742 [PubMed - indexed for MEDLINE]

75: Yakugaku Zasshi. 1993 Apr;113(4):316-20.

[Quantitative analysis of deacylgymnemic acid by high-performance liquid

[Article in Japanese]

Suzuki K, Ishihara S, Uchida M, Komoda Y.

Tokiwa Phytochemical Co., Ltd., Chiba, Japan.

A method of the quantitative analysis was established for the determination of
deacylgymnemic acid (DAGA) in the alkaline hydrolysate of the sample containing
gymnemic acids which are ingredients of Gymnema sylvestre R. BR. leaves, by
means of high-performance liquid chromatography. This method was used for
comparing the contents of gymnemic acids in various samples. The amount of
gymnemic acids analyzed as DAGA in 70% ethanol extract of dry leaves was about
twice that in hot water extract. The commercial health-supplemental foods of
five companies were investigated for the contents of gymnemic acids as DAGA and
there were large differences from 38 to 251 mg in the dosage per day recommended
by each company.

Publication Types:
English Abstract

PMID: 8492295 [PubMed - indexed for MEDLINE]

76: J Nutr. 1992 Dec;122(12):2367-73.

An extract of Gymnema sylvestre leaves and purified gymnemic acid inhibits
glucose-stimulated gastric inhibitory peptide secretion in rats.

Fushiki T, Kojima A, Imoto T, Inoue K, Sugimoto E.

Department of Food Science and Technology, Faculty of Agriculture, Kyoto
University, Japan.

Gastric inhibitory peptide release into the portal vein in response to duodenal
infusion of D-glucose was studied in the presence of a leaf extract of Gymnema
sylvestre, purified gymnemic acid and inhibitors of some putative glucose
sensors and carriers in the intestinal lumen. Intraduodenal infusion of
D-glucose significantly increased the portal immunoreactive gastric inhibitory
peptide concentration in a dose-dependent manner. The increase in the portal
immunoreactive gastric inhibitory peptide induced by glucose was significantly
depressed by concomitantly infused leaf extract of Gymnema sylvestre, purified
gymnemic acid and phlorizin but not by cytochalasin B. Mannoheptulose, which
inhibits glycolysis, and procaine and lidocaine, which inhibit the vagal
glucoreceptor in the lumen, did not affect portal immunoreactive gastric
inhibitory peptide concentrations. These results suggest that a glucose
receptor, which interacts with the leaf extract of Gymnema sylvestre, purified
gymnemic acid and phlorizin, exists for the release of immunoreactive gastric
inhibitory peptide and that the glucose receptor for gastric inhibitory peptide
release is not likely to be identical with a glucose transporter or a vagal
glucoreceptor in the lumen.

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

PMID: 1453221 [PubMed - indexed for MEDLINE]

77: Biochim Biophys Acta. 1992 Nov 17;1137(3):274-8.

Inhibitory effects of pectic substances on activated hyaluronidase and histamine
release from mast cells.

Sawabe Y, Nakagomi K, Iwagami S, Suzuki S, Nakazawa H.

Osaka Prefectural Institute of Public Health, Japan.

In this paper, we report the effect of pectic substances and D-galacturonic
acid, the main constituent of pectic substances, on activated hyaluronidase and
histamine release from mast cells. Although D-galacturonic acid itself showed no
inhibition, IC50 values of hyaluronidase inhibition were correlated with the
D-galacturonic-acid content of pectic substances. It was thought that the
polymerization of D-galacturonic acid was necessary for inhibition of activated
hyaluronidase. This type of inhibition was suggested to be non-competitive by
the Lineweaver-Burk plot. Furthermore, pectic substances, including those
purified from Gymnema sylvestre, inhibited histamine release from isolated rat
peritoneal mast cells, which had been induced by the antigen. These results
suggest that pectic substances may have anti-allergic activities.

PMID: 1280162 [PubMed - indexed for MEDLINE]

78: Chem Pharm Bull (Tokyo). 1992 Jun;40(6):1366-75.

Isolation and structure elucidation of gymnemic acids, antisweet principles of
Gymnema sylvestre.

Liu HM, Kiuchi F, Tsuda Y.

Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.

The structure of gymnemagenin (3 beta,16 beta,21 beta,22
alpha,23,28-hexahydroxy-olean-12-ene), the sapogenin of the antisweet principles
of Gymnema sylvestre, was established by X-ray analysis of the 3 beta,23;21
beta,22 alpha-di-O-isopropylidene derivative. On the basis of this result, the
structure of deacylgymnemic acid was elucidated as the 3-O-beta-glucuronide from
the carbon-13 nuclear magnetic resonance spectra. Five antisweet principles,
gymnemic acid-III, -IV, -V, -VIII, and -IX, were isolated in pure states from
the hot water extract of leaves of Gymnema sylvestre. Of these, three (GA-III,
-IV, and -V) were known, while two (GA-VIII and -IX) were new compounds. The
structures of GA-VIII and -IX were elucidated as
3'-O-beta-D-arabino-2-hexulopyranosyl gymnemic acid-III and -IV, respectively.

PMID: 1327559 [PubMed - indexed for MEDLINE]

79: J Biochem (Tokyo). 1992 Jan;111(1):109-12.

Amino acid sequence of sweet-taste-suppressing peptide (gurmarin) from the
leaves of Gymnema sylvestre.

Kamei K, Takano R, Miyasaka A, Imoto T, Hara S.

Department of Chemistry and Material Technology, Faculty of Engineering and
Design, Kyoto Institute of Technology.

The complete amino acid sequence of a sweet-taste-suppressing peptide, gurmarin,
from the leaves of Gymnema sylvestre was determined by the Edman analysis of
peptides derived from digests obtained with Staphylococcus aureus V8 protease,
pyroglutamyl aminopeptidase, and lysyl endopeptidase. Gurmarin consists of 35
amino acid residues with an amino-terminal pyroglutamyl residue and has the
molecular weight of 4,209. Gurmarin has no significant homology with other known

PMID: 1607357 [PubMed - indexed for MEDLINE]

80: Crit Rev Food Sci Nutr. 1992;32(3):231-52.

Characteristics of antisweet substances, sweet proteins, and sweetness-inducing

Kurihara Y.

Department of Chemistry, Faculty of Education, Yokohama National University,

Recent studies on structures and functions of sweetness-inhibiting substances
(gymnemic acid, ziziphin, and gurmarin); sweet proteins (monellin, thaumatin and
mabinlin); and taste-modifying proteins (miraculin and curculin) were reviewed.
Several gymnemic acid homologues and gurmarin were purified from the leaves of
Gymnema sylvestre and their structures were determined. Ziziphin was also
purified from leaves of Ziziphus jujuba. Gymnemic acid and ziziphin are
glycoside of triterpenes that suppress sweetness in human, while gurmarin is a
peptide having antisweet activity in rat. Mabinlin is a heat-stable sweet
protein. The whole amino acid sequence and the position of disulfide bridges of
mabinlin were determined. Miraculin has the unusual property of modifying a sour
taste into a sweet taste. Curculin elicits a sweet taste. In addition, water and
sour substance elicit a sweet taste after curculin. Their amino acid sequences
and subunit structures were determined. These proteins are expected to be used
as low-calorie sweeteners.

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

PMID: 1418601 [PubMed - indexed for MEDLINE]

81: Physiol Behav. 1991 May;49(5):919-25.

Electrophysiological and behavioral studies on the taste of umami substances in
the rat.

Yamamoto T, Matsuo R, Fujimoto Y, Fukunaga I, Miyasaka A, Imoto T.

Department of Behavioral Physiology, Faculty of Human Sciences, Osaka
University, Japan.

Electrophysiological and behavioral experiments were performed to reveal taste
properties of "umami" substances such as monosodium glutamate (MSG) and disodium
inosine monophosphate (IMP) in rats. To eliminate the taste effects of Na ions
contained in these umami substances, we dissolved them in 0.01 mM amiloride,
which is known to block sodium responses. In the electrophysiological study,
taste responses of the whole chorda tympani nerve were recorded. The magnitude
of responses to MSG (or IMP) at concentrations below 0.1 M (or 0.01 M) was less
than 10% of that to 0.1 M NaCl. On the other hand, the mixtures of MSG and IMP
showed responses 2-7 times larger than the arithmetric sum of the responses to
each component of the mixtures. A new sweet taste inhibitor (Gymnema sylvestre
extract) strongly suppressed neural responses to mixtures of MSG and IMP as well
as sucrose, but only weakly or negligibly to individual solutions of these umami
substances. In the behavioral study, the brief exposure two-bottle preference
test and conditioned taste aversion paradigm were used. MSG was most preferred
at 0.3 M (preference ratio = 57%), IMP, at 0.01 M (61%), and both were less
preferred or rejected at higher concentrations. In contrast, mixtures of MSG and
IMP were more preferred at a broad concentration range (e.g., 82% for 0.1 M MSG
+ 0.01 M IMP). Aversive conditioning to umami substances was generalized to
sucrose, and vice versa, but not to 0.1 M NaCl, 0.01 M HCl, and 0.1 mM quinine

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

PMID: 1653433 [PubMed - indexed for MEDLINE]

82: Comp Biochem Physiol A. 1991;100(2):309-14.

A novel peptide isolated from the leaves of Gymnema sylvestre--I.
Characterization and its suppressive effect on the neural responses to sweet
taste stimuli in the rat.

Imoto T, Miyasaka A, Ishima R, Akasaka K.

Department of Physiology, Tottori University School of Medicine, Yonago, Japan.

1. A new substance that suppressed selectively the neural responses of the rat
to sweet taste stimuli was isolated from the leaves of Gymnema sylvestre. 2. The
substance was proved to be a peptide consisting of 35 amino acids and having a
molecular weight of about 4,000. 3. The inhibitory effect on the sweet responses
appeared after treating the tongue surface with the peptide at a concentration
of more than 1 x 10(-6) M.

PMID: 1685952 [PubMed - indexed for MEDLINE]

83: J Ethnopharmacol. 1990 Oct;30(3):295-300.

Antidiabetic effect of a leaf extract from Gymnema sylvestre in
non-insulin-dependent diabetes mellitus patients.

Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER.

Department of Biochemistry, Postgraduate Institute of Basic Medical Sciences
Madras, India.

The effectiveness of GS4, an extract from the leaves of Gymnema sylvestre, in
controlling hyperglycaemia was investigated in 22 Type 2 diabetic patients on
conventional oral anti-hyperglycaemic agents. GS4 (400 mg/day) was administered
for 18-20 months as a supplement to the conventional oral drugs. During GS4
supplementation, the patients showed a significant reduction in blood glucose,
glycosylated haemoglobin and glycosylated plasma proteins, and conventional drug
dosage could be decreased. Five of the 22 diabetic patients were able to
discontinue their conventional drug and maintain their blood glucose homeostasis
with GS4 alone. These data suggest that the beta cells may be
regenerated/repaired in Type 2 diabetic patients on GS4 supplementation. This is
supported by the appearance of raised insulin levels in the serum of patients
after GS4 supplementation.

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

PMID: 2259217 [PubMed - indexed for MEDLINE]

84: J Ethnopharmacol. 1990 Oct;30(3):281-94.

Use of Gymnema sylvestre leaf extract in the control of blood glucose in
insulin-dependent diabetes mellitus.

Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha
Shanmugasundaram K, Kizar Ahmath B.

Department of Biochemistry, University of Madras, India.

GS4, a water-soluble extract of the leaves of Gymnema sylvestre, was
administered (400 mg/day) to 27 patients with insulin-dependent diabetes
mellitus (IDDM) on insulin therapy. Insulin requirements came down together with
fasting blood glucose and glycosylated haemoglobin (HbA1c) and glycosylated
plasma protein levels. While serum lipids returned to near normal levels with
GS4 therapy, glycosylated haemoglobin and glycosylated plasma protein levels
remained higher than controls. IDDM patients on insulin therapy only showed no
significant reduction in serum lipids, HbA1c or glycosylated plasma proteins
when followed up after 10-12 months. GS4 therapy appears to enhance endogenous
insulin, possibly by regeneration/revitalisation of the residual beta cells in
insulin-dependent diabetes mellitus.

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

PMID: 2259216 [PubMed - indexed for MEDLINE]

85: J Ethnopharmacol. 1990 Oct;30(3):265-79.

Possible regeneration of the islets of Langerhans in streptozotocin-diabetic
rats given Gymnema sylvestre leaf extracts.

Shanmugasundaram ER, Gopinath KL, Radha Shanmugasundaram K, Rajendran VM.

Department of Biochemistry, University of Madras, India.

Two water soluble extracts, GS3 and GS4, obtained from the leaves of Gymnema
sylvestre, were tested in streptozotocin treated rats for their effects on blood
glucose homeostasis and pancreatic endocrine tissue. In the diabetic rats,
fasting blood glucose levels returned to normal after 60 days of GS3 and after
20 days of GS4 oral administration. Blood collected during the conduct of oral
glucose tolerance tests was used to assay for serum insulin. GS3 and GS4 therapy
led to a rise in serum insulin to levels closer to normal fasting levels. In
diabetic rat pancreas, both GS3 and GS4 were able to double the islet number and
beta cell number. This herbal therapy appears to bring about blood glucose
homeostasis through increased serum insulin levels provided by
repair/regeneration of the endocrine pancreas.

Publication Types:
In Vitro

PMID: 2259215 [PubMed - indexed for MEDLINE]

86: Diabetes Res Clin Pract. 1990 May-Jun;9(2):143-8.

Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats.

Okabayashi Y, Tani S, Fujisawa T, Koide M, Hasegawa H, Nakamura T, Fujii M,
Otsuki M.

Second Department of Internal Medicine, Kobe University School of Medicine,

Effect of Gymnema sylvestre, R.Br. (G. sylvestre; GS4) on glucose homeostasis
was studied in rats. In the first set of experiments, the acute effect of GS4
was examined in both non-diabetic and streptozocin (30 mg/kg)-induced mildly
diabetic rats. Administration of 1 g/kg body weight of GS4 to 18-h fasted
non-diabetic rats significantly attenuated the serum glucose response to oral
administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in
GS4-administered rats was lower, but not significantly, than that in control
rats. In mildly diabetic rats, a 60 min increment in serum glucose
concentrations was significantly reduced by GS4 administration. No IRI response
was observed in these diabetic rats irrespective of GS4 administration. In the
second set of experiments, the chronic effect of GS4 was examined in mildly
diabetic rats. Two weeks after the induction of diabetes, the rats were divided
into two groups that had similar impairment of glucose tolerance assessed by an
oral glucose loading test. The rats were fed for 32-35 days with either a
control diet or a diet supplemented with GS4. After 4 weeks, GS4 showed a
tendency to reduce the serum glucose concentrations in the fed state and to
improve the glucose tolerance. Gain in body weight, food intake, pancreas weight
and the pancreatic contents of IRI, protein, amylase and trypsinogen were
unaltered in the GS4-treated group compared with the control. These results
suggest the usefulness of G. sylvestre in the treatment of certain classes of
non-insulin-dependent diabetes mellitus.

PMID: 1695875 [PubMed - indexed for MEDLINE]

87: J Pak Med Assoc. 1988 Nov;38(11):289-95.

Effect of Grewia asiatica, Gossypium herbacium and Gymnema sylvestre on blood
glucose, cholesterol and triglycerides levels in normoglycaemic and alloxan
diabetic rabbits.

Dogar IA, Ali M, Yaqub M.

PMID: 3148751 [PubMed - indexed for MEDLINE]

88: J Ethnopharmacol. 1986 Nov;18(2):143-6.

Effect of feeding Gymnema sylvestre leaves on blood glucose in beryllium nitrate
treated rats.

Prakash AO, Mathur S, Mathur R.

The feeding of powdered leaves of Gymnema sylvestre in the diet of rats for 10
days prior and 15 days after i.v. beryllium nitrate significantly protected the
animals from the full fall of blood glucose seen in rats receiving beryllium
nitrate alone. The feeding of the leaves for 25 days to normal rats did not
alter blood glucose significantly. The leaves may contain a principle that could
be useful as a prophylactic against beryllium toxicity.

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

PMID: 3560992 [PubMed - indexed for MEDLINE]

89: Isr J Med Sci. 1985 Jun;21(6):540-2.

Hypoglycemic and life-prolonging properties of Gymnema sylvestre leaf extract in
diabetic rats.

Srivastava Y, Nigam SK, Bhatt HV, Verma Y, Prem AS.

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

PMID: 4019152 [PubMed - indexed for MEDLINE]

90: Indian J Physiol Pharmacol. 1983 Jul-Sep;27(3):257-8.

Hypoglycaemic activity of an indigenous drug (Gymnema sylvestre, 'Gurmar') in
normal and diabetic persons.

Khare AK, Tondon RN, Tewari JP.

Publication Types:
Comparative Study

PMID: 6668058 [PubMed - indexed for MEDLINE]

91: J Ethnopharmacol. 1983 Mar;7(2):205-34.

Enzyme changes and glucose utilisation in diabetic rabbits: the effect of
Gymnema sylvestre, R.Br.

Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER.

The administration of the dried leaf powder of Gymnema sylvestre regulates the
blood sugar levels in alloxan diabetic rabbits. G. sylvestre therapy not only
produced blood glucose homeostasis but also increased the activities of the
enzymes affording the utilisation of glucose by insulin dependent pathways: it
controlled phosphorylase levels, gluconeogenic enzymes and sorbitol
dehydrogenase. The uptake and incorporation of [14C] glucose into the glycogen
and protein are increased in the liver, kidney and muscle in G. sylvestre
administered diabetic animals when compared to the untreated diabetic animals.
Pathological changes initiated in the liver during the hyperglycemic phase are
reversed by controlling hyperglycemia by G. sylvestre. G. sylvestre, a herb used
for the control of diabetes mellitus in several parts of India, appears to
correct the metabolic derangements in diabetic rabbit liver, kidney and muscle.

PMID: 6865451 [PubMed - indexed for MEDLINE]

92: Physiol Behav. 1983 Jan;30(1):1-9.

Effects of sweetness perception and caloric value of a preload on short term

Brala PM, Hagen RL.

To determine the effects of calories and sweetness perception on intake, fasted
normal weight subjects drank a preload sweetened with sucrose (1.1 g/kg) or
L-asparthyl-L-phenylalanyl-methyl ester (Aspartame, 0.011 g/kg), or with no
added sweetener. Sweetness perception of the load was reduced in half of the
subjects by oral application of Gymnema sylvestre extracts. One hour after the
preload, a meal of snack foods was presented and amounts of nutrients eaten were
calculated. Subjects whose perception of sweetness had been decreased for the
preload ate less total and sweet calories than did those with normal perception.
Calories did not affect intake. The effect of calories and perception of the
load was also assessed on variables presumed to correlate with satiety. Sucrose
pleasantness ratings were not related to calories, perception or intake.
Subjects' estimates of the amount of milkshake that they would drink if given
the opportunity to do so and hunger ratings were related to overall intake and
carbohydrate intake, respectively. The findings indicate that hedonistic aspects
of taste are of greater importance than calories in determining short term

PMID: 6836034 [PubMed - indexed for MEDLINE]

93: Indian J Exp Biol. 1981 Aug;19(8):715-21.

Studies on protein-bound polysaccharide components & glycosaminoglycans in
experimental diabetes--effect of Gymnema sylvestre, R.Br.

Rathi AN, Visvanathan A, Shanmugasundaram KR.

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

PMID: 7309156 [PubMed - indexed for MEDLINE]

94: Pharmacol Res Commun. 1981 May;13(5):475-86.

The insulinotropic activity of Gymnema sylvestre, R. Br. An Indian medical herb
used in controlling diabetes mellitus.

Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER.

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

PMID: 7027275 [PubMed - indexed for MEDLINE]

95: J Comp Physiol Psychol. 1979 Jun;93(3):538-47.

Evidence for neural inhibition in bittersweet taste mixtures.

Lawless HT.

Three lines of evidence from psychophysical experiments implied that mutual
suppression of bitter and sweet tastes is due to neural inhibition rather than
chemical interactions in solution or competition of molecules for common
receptor sites. Removal of sweetness from bittersweet mixtures caused the
bitterness to increase. This was accomplished by adaptation to sucrose or by
treatment with Gymnema sylvestre, neither of which affect the concentration of
sucrose on the tongue. Such increases in the bitterness of mixtures, independent
of the concentration of the sweet masking substance, are difficult to reconcile
with suppression by means of chemical interactions. Similar dependence of
suppression on perceived intensity (and independence from concentration) was
observed with mixtures of phyenylthiocarbamide and sucrose. Tasters of
phenylthiocarbamide showed stronger suppression of sweetness than nontasters.
This result was also inconsistent with molecular interactions causing
suppression, which would have resulted in the same degree of suppression for the
two groups. Instead, these findings support neural explanations of mixture
suppression, such as antidromic inhibition or occlusion.

Publication Types:
Comparative Study

PMID: 479396 [PubMed - indexed for MEDLINE]

96: Ala J Med Sci. 1977 Apr;14(2):150-6.

Sensory effects of Gymnema sylvestre: implications of Mass action and chemical

Yackzan KS, Stoll PJ.

PMID: 855895 [PubMed - indexed for MEDLINE]

97: J Agric Food Chem. 1973 Sep-Oct;21(5):899-903.

Gymnemic acid, the antisaccharine principle of Gymnema sylvestre. Studies on the
isolation and heterogeneity of gymnemic acid A1.

Dateo GP Jr, Long L Jr.

PMID: 4733385 [PubMed - indexed for MEDLINE]

98: Comp Biochem Physiol A. 1972 Oct 1;43(2):381-91.

Comparative electrocardiography in lizards: effects of temperature and Gymnema
sylvestre fractions.

Yackzan KS, Yousef MK, Dill DB.

PMID: 4145248 [PubMed - indexed for MEDLINE]

99: J Pharm Sci. 1971 Feb;60(2):190-3.

Constituents from Gymnema sylvestre leaves. 8. Isolation, chemistry, and
derivatives of gymnemagenin and gymnestrogenin.

Rao GS, Sinsheimer JE.

PMID: 5572438 [PubMed - indexed for MEDLINE]

100: Physiol Behav. 1970 Dec;5(12):1379-84.

Effects of Gymnema sylvestre on complex tastes elicited by amino acids and

Meiselman HL, Halpern BP.

PMID: 5524525 [PubMed - indexed for MEDLINE]

101: Physiol Behav. 1970 Aug;5(8):945-8.

Human judgments of Gymnema sylvestre and sucrose mixtures.

Meiselman HL, Halperin BP.

PMID: 5522511 [PubMed - indexed for MEDLINE]

102: J Pharm Sci. 1970 May;59(5):629-32.

Constituents from Gymnema sylvestre leaves. VI. Acylated genins of the gymnemic
acids--isolated and preliminary characterization.

Sinsheimer JE, Rao GS.

PMID: 5450284 [PubMed - indexed for MEDLINE]

103: J Pharm Sci. 1970 May;59(5):622-8.

Constuents from Gymnema sylvestre leaves. V. Isolation and preliminary
characterization of the gymnemic acids.

Sinsheimer JE, Rao GS, McIlhenny HM.

PMID: 5446417 [PubMed - indexed for MEDLINE]

104: Ala J Med Sci. 1970 Jan;7(1):77-9.

Biological effects of Gymnema sylvestre fractions. 3. Electrophysiology-in vitro
gastric membrane findings.

Yackzan KS.

Publication Types:
In Vitro

PMID: 5428555 [PubMed - indexed for MEDLINE]

105: Ala J Med Sci. 1969 Oct;6(4):455-63.

Biological effects of Gymnema sylvestre fractions. II. Electrophysiology--effect
of gymnemic acid on taste receptor response.

Yackzan KS.

PMID: 5363232 [PubMed - indexed for MEDLINE]

106: Nature. 1969 Jul 5;223(5201):94-5.

Inhibition of the sweet taste by Gymnema sylvestre.

Warren RP, Warren RM, Weninger MG.

Publication Types:
Clinical Trial
Controlled Clinical Trial

PMID: 5792442 [PubMed - indexed for MEDLINE]

107: Helv Chim Acta. 1968;51(6):1235-42.

[Gymnestrogenin, a new pentahydroxytriterpene from the leaves of Gymnema
sylvestre R.Br.]

[Article in German]

Stocklin W.

PMID: 5680734 [PubMed - indexed for MEDLINE]

108: J Pharm Sci. 1967 Jun;56(6):732-6.

Constituents from Gymnema sylvestre leaves. II. Nitrogenous compounds.

Sinsheimer JE, McIlhenny HM.

PMID: 6039815 [PubMed - indexed for MEDLINE]

109: Bull Calcutta Sch Trop Med. 1966 Oct;14(4):126-7.

Crystalline saponin from Gymnema sylvestre.

Chakravarti RN, Chakravarti D, Itty MI.

PMID: 6003983 [PubMed - indexed for MEDLINE]

110: J Pharm Sci. 1965 Oct;54(10):1541-4.

Constituents from Gymnema sylvestre leaves.

Manni PE, Sinsheimer JE.

PMID: 5883239 [PubMed - indexed for MEDLINE]

111: Indian J Med Res. 1964 Feb;52:200-7.



PMID: 14122605 [PubMed - OLDMEDLINE]

112: Indian J Med Sci. 1963 Jun;17:501-5.

Effect of Gymnema sylvestre and Pterocarpus marsupium on glucose tolerance in
albino rats.


PMID: 13951326 [PubMed - indexed for MEDLINE]

113: Indian J Med Sci. 1961 Nov;15:883-7.

Inhibitory effect of Gymnema sylvestre (Gurmar) on adrenaline-induced
hyperglycemia in rats.


PMID: 13903013 [PubMed - OLDMEDLINE]

114: Indian J Med Sci. 1961 Aug;15:656-9.

Inhibitory effect of Gymnema sylvestre (Gurmar) on adreno-hypophysial activity
in rats.


PMID: 13709825 [PubMed - OLDMEDLINE]