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STUDIES AVAILABLE OF GURMAR

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1.[Structural alterations in pancreatic islets in streptozotocin-induced diabetic rats treated with of bioactive additive on the basis of Gymnema sylvestre]

[Article in Russian]

[No authors listed]

The structural alterations in pancreatic islets in streptozotocin-induced diabetic rats were studied after the administration of Gymnema sylvestre extract or its composition. Diabetes mellitus was modeled by daily injection of streptozotocin (20 mg/kg for 5 days) and single injection of 0.2 ml of complete Freund's adjuvant, Only the animals with the blood glucose level exceeding 15 mmol/l were included in the experiment. B- and A-endocrinocytes were demonstrated using immunocytochemistry. The proportions of the area of the pancreatic islets, occupied by B- and A-endocrinocytes, as well as the volume fraction of the pancreatic islets within the pancreas, were determined. In the model of streptozotocin-induced diabetes, the part of the total islet area occupied by B-endocrinocytes, was diminished in the pancreatic islets located in all the zones of the gland. Prophylactic administration of Gymnema sylvestre extract or its composition tended to restore the area occupied by B-endocrinocytes in the pancreatic islets. These results indicate the equal potency of the composition and extract of Gymnema sylvestre to induce the regeneration of B-endocrinocytes.

Publication Types: PMID: 19069418 [PubMed - in process]

2.Two new triterpenoid saponins from Gymnema sylvestre.

Zhu XM, Xie P, Di YT, Peng SL, Ding LS, Wang MK.

Chengdu Institute of Biology, the Chinese Academy of Sciences, Chengdu 610041, China.

Two new oleanane-type triterpenoid saponins, gymnemoside-W1 and W2, together with seven known compounds were isolated from the leaves of Gymnema sylvestre R. Br. By means of spectral and chemical analysis, the structures of the new compounds were elucidated as 16 beta-hydroxyl olean-12-en-3-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl]-28-O-beta-D-glucopyranoside(1) and 16 beta,21 beta,28-trihydroxyl-olean-12-ene-3-O-glucoronopyranoside (2). The EtOH/H(2)O extracts of this plant were shown to be able to inhibit glucose absorption in rats.

PMID: 18713427 [PubMed - indexed for MEDLINE]

3.Efficacy of dietary supplementation with botanicals on carbohydrate metabolism in humans.

Cefalu WT, Ye J, Wang ZQ.

Division of Nutrition and Chronic Diseases, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. William.Cefalu@pbrc.edu

Botanical products are widely used in nutritional supplementation for promotion of health or prevention of diseases. With the high prevalence of obesity and type 2 diabetes, abnormalities in carbohydrate metabolism are common in the general population and obtaining glycemic control is important in reducing the complications of diabetes. If shown to be effective, botanical products have a unique position in potentially aiding the general public in regard to obesity and diabetes. They can be obtained "over-the-counter" and may have less side effects compared to many synthetic drugs. Although most of the popular botanicals have a long history in folk medicine, there is paucity of data regarding their efficacy and safety, particularly as it relates to human studies. In this review, we discuss the data that was available in the literature for nine botanicals that are frequently promoted to help manage blood glucose. They are Bitter Melon (Momordica charantia), Fenugreek (trigonella foenum graecum), Gymnema Sylvestre, Ivy Gourd (Coccinia indica), Nopal or Prickly Pear Cactus (Opuntia streptacantha), Ginseng, Aloe Vera, Russian Tarragon (Artemisia dracunculus), and Garlic (Allium sativum). The discussion is emphasized on the clinical aspect of these botanicals. Due to the lack of sufficient evidence from clinical studies for any of the botanicals reviewed, it is premature to actively recommend use of any particular herb to treat either glucose or other risk factors. Thus, well defined randomized clinical trials are warranted in this area.

Publication Types: PMID: 18537692 [PubMed - indexed for MEDLINE]

4.Gymnema sylvestre: A Memoir.

Kanetkar P, Singhal R, Kamat M.

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

Gymnema sylvestre is regarded as one of the plants with potent anti diabetic properties. This plant is also used for controlling obesity in the form of Gymnema tea. The active compound of the plant is a group of acids termed as gymnemic acids. It has been observed that there could be a possible link between obesity, Gymnemic acids and diabetes. This review will try to put forth an overall idea about the plant as well as present a molecular perspective linking the common medicine to the most common metabolic disorders.

PMID: 18193099 [PubMed - in process]  PMCID: PMC2170951

5.Gurmarin sensitivity of sweet taste responses is associated with co-expression patterns of T1r2, T1r3, and gustducin.

Shigemura N, Nakao K, Yasuo T, Murata Y, Yasumatsu K, Nakashima A, Katsukawa H, Sako N, Ninomiya Y.

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

Gurmarin (Gur) is a peptide that selectively suppresses sweet taste responses in rodents. The inhibitory effect of Gur differs among tongue regions and mouse strains. Recent studies demonstrated that co-expression levels of genes controlling sweet receptors (T1r2/T1r3 heterodimer) versus Galpha-protein, gustducin, are much lower in Gur-insensitive posterior circumvallate papillae than in Gur-sensitive anterior fungiform papillae. Here, we investigated the potential link of Gur-sensitivity with the co-expression for T1r2/T1r3 receptors and gustducin by comparing those of taste tissues of Gur-sensitive (B6, dpa congenic strains) and Gur-weakly-sensitive (BALB) strains. The results indicated that co-expression ratios among T1r2, T1r3, and gustducin in the fungiform papillae were significantly lower in Gur-weakly-sensitive BALB mice than in Gur-sensitive B6 and dpa congenic mice. This linkage between Gur-sensitivity and co-expression for T1r2/T1r3 receptors versus gustducin suggests that gustducin may be a key molecule involved in the pathway for Gur-sensitive sweet responses.

Publication Types: PMID: 18174025 [PubMed - indexed for MEDLINE]

6.Gymnema sylvestre for diabetes mellitus: a systematic review.

Leach MJ.

School of Health Sciences, University of South Australia, North Terrace Adelaide, South Australia. Matthew.Leach@unisa.edu.au

Across the globe, there are an estimated 150 million people suffering from diabetes mellitus. Each of these people is at increased risk of developing a number of complications, each of which are associated with a reduction in quality of life and an increase in individual morbidity and mortality. However, despite these psychosocial implications, as well as the financial burden associated with the management of the disease, existing treatment options are costly, and have limited, palliative effects. One treatment that is emerging as a potential panacea for the management of diabetes is Gymnema sylvestre. Yet, what evidence is there to support the use of this extract? In order to answer this question, a systematic review of the literature and a discussion of the best available evidence on gymnema are needed. The findings of such a review are presented in this paper.

Publication Types:  PMID: 18047444 [PubMed - indexed for MEDLINE]

7.Recovery of two independent sweet taste systems during regeneration of the mouse chorda tympani nerve after nerve crush.

Yasumatsu K, Kusuhara Y, 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.

In rodents, section of the taste nerve results in degeneration of the taste buds. Following regeneration of the cut taste nerve, however, the taste buds reappear. This phenomenon can be used to study the functional reformation of the peripheral neural system responsible for sweet taste. In this study we examined the recovery of sweet responses by the chorda tympani (CT) nerve after nerve crush as well as inhibition of these responses by gurmarin (Gur), a sweet response inhibitor. After about 2 weeks of CT nerve regeneration, no significant response to any taste stimuli could be observed. At 3 weeks, responses to sweet stimuli reappeared but were not significantly inhibited by Gur. At 4 weeks, Gur inhibition of sweet responses reached statistically significant levels. Thus, the Gur-sensitive (GS) component of the sweet response reappeared about 1 week later than the Gur-insensitive (GI) component. Moreover, single CT fibers responsive to sucrose could be classified into distinct GS and GI groups at 4 weeks. After 5 weeks or more, responses to sweet compounds before and after treatment with Gur became indistinguishable from responses in the intact group. During regeneration, the GS and GI components of the sucrose response could be distinguished based on their concentration-dependent responses to sucrose. These results suggest that mice have two different sweet-reception systems, distinguishable by their sensitivity to Gur (the GS and GI systems). These two sweet-reception systems may be reconstituted independently during regeneration of the mouse CT nerve.

Publication Types:  PMID: 17714496 [PubMed - indexed for MEDLINE]

8.[Unconventional antidiabetic agents]

[Article in German]

Rustenbeck I.

Institut für Pharmakologie und Toxikologie, Technische Universität Braunschweig. i.rustenbeck@tu-bs.de

The current pharmacological therapy of type 2 diabetes reduces the risk of diabetic complications, but is not able to achieve a long-lasting normalization of the metabolic disorder. Thus diabetic patients in increasing numbers are taking dietary supplements and herbs from which they expect additional health benefits. These unconventional antidiabetic agents consist mainly in trace metals like chromium, vanadium and zinc and a heterogeneous group of traditionally used antidiabetic herbs (e. g. Momordica charantia, Gymnema sylvestre, Trigonella foenum-graecum) often derived from the ayurvedic medicine. In this overview the current evidence for the antidiabetic effect is presented. The trace elements chromium and vanadium have a number of potentially antidiabetic actions in vitro, however, the results obtained with diabetic patients are not convincing so far. Similarly, the available data on the therapeutic use of herbs suggest that in principle a number of them possess a blood glucose-lowering effect, but at present no firm conclusions as to their efficacy and safety can be made. To set up reliable dose-effect relationships requires the identification of the relevant antidiabetic molecules as was apparently achieved by isolating 4-hydroxyisoleucine from the seeds of T. foenum-graecum. This requirement is also valid in the case of the antidiabetic action of cinnamon. Coffee and a moderate alcohol consumption were found to be surprisingly effective in lowering the risk of type 2 diabetes manifestation, their effect being roughly equal to that of conventional drugs used in diabetes prevention trials. Diabetic patients should inform their physician about the use of unconventional agents and should be warned against uncontrolled starting or stopping their use.

Publication Types:  PMID: 17484443 [PubMed - indexed for MEDLINE]

9.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 98028, USA. rbradley@bastyr.edu

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.

Publication Types:  PMID: 17309390 [PubMed - indexed for MEDLINE]

10.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:  PMID: 17144249 [PubMed - indexed for MEDLINE]

11.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: PMID: 16765321 [PubMed - indexed for MEDLINE]

12.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]

13.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. luo_jsps@hotmail.com

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 promoted 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.

Publication Types:  PMID: 16691318 [PubMed - indexed for MEDLINE]

14.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 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-galactopyranoside, has been synthesized in good yield and stereoselectivity using N-iodosuccinimide and HClO4-silica promoted glycosylations of thioglycoside donors.

PMID: 16603139 [PubMed - indexed for MEDLINE]

15.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. ikukokim@pa.ctt.ne.jp

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]

16.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. lab9@gawab.com

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]

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

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. preusshg@georgetown.edu

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:  PMID: 16366421 [PubMed - indexed for MEDLINE]

18.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. rhirano@ndmc.ac.jp

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]

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

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

College of Pharmaceutical Sciences, Manipal, Karnataka, India.

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

Publication Types:  PMID: 16106394 [PubMed - indexed for MEDLINE]

20.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: PMID: 15932937 [PubMed - indexed for MEDLINE]

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

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

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

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:  PMID: 15707781 [PubMed - indexed for MEDLINE]

22.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: PMID: 15587591 [PubMed - indexed for MEDLINE]

23.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]

25.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. puratchi_v@rediffmail.com

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:  PMID: 15202600 [PubMed - indexed for MEDLINE]

26.[Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar rats]

[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: PMID: 15168555 [PubMed - indexed for MEDLINE]

27.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. preusshg@georgetown.edu

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:  PMID: 15056124 [PubMed - indexed for MEDLINE]

28.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 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-galactopyranoside (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]

29.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 coli.

PMID: 14630178 [PubMed - indexed for MEDLINE]

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

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: PMID: 12857006 [PubMed - indexed for MEDLINE]

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

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:

PMID: 12714446 [PubMed - indexed for MEDLINE]

32.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. chris@utmem.edu

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: PMID: 12702710 [PubMed - indexed for MEDLINE]

33.Systematic review of herbs and dietary supplements for glycemic control in diabetes.

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. gyeh@caregroup.harvard.edu

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]

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

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]

35.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. jkgrover@hotmail.com

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]

36.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: PMID: 12006375 [PubMed - indexed for MEDLINE]

37.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. imotot@grape.med.tottori-u.ac.jp

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: PMID: 11697741 [PubMed - indexed for MEDLINE]

38.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, India.

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: PMID: 11697445 [PubMed - indexed for MEDLINE]

39.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. nakakiyo@dent.asahi-u.ac.jp

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: PMID: 11508708 [PubMed - indexed for MEDLINE]

40.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 beta-O-benzoylsitakisogenin 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 activity.

Publication Types:  PMID: 11430009 [PubMed - indexed for MEDLINE]

41.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. noshigematsu@fancl.co.jp

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 rats.

PMID: 11411567 [PubMed - indexed for MEDLINE]

42.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. noshigematsu@fancl.co.jp

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]

43Antihyperglycemic 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]

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

Harada S, Kasahara Y.

Department of Oral Physiology, Kagoshima University Dental School, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. harada@hy.hal.kagoshima-u.ac.jp

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 substances.

Publication Types: PMID: 10848518 [PubMed - indexed for MEDLINE]

45.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-glucuronopyranoside, 3-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, oleanolic acid 3-O-beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl(1-->6)-beta-D- 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: PMID: 10820799 [PubMed - indexed for MEDLINE]

46.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. sanctum.

Publication Types:  PMID: 10617074 [PubMed - indexed for MEDLINE]

47.Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability.

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: PMID: 10556769 [PubMed - indexed for MEDLINE]

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

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: PMID: 10491100 [PubMed - indexed for MEDLINE]

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

Katsukawa H, Imoto T, Ninomiya Y.


Department of Oral Physiology, School of Dentistry, Asahi University, Hozumi, Gifu, Japan. kat@dent.asahi-u.ac.jp

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]

50.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:

PMID: 10368423 [PubMed - indexed for MEDLINE]

51.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:

PMID: 10356090 [PubMed - indexed for MEDLINE]

52.Inhibitory effect of gymnemic acid on intestinal absorption of oleic acid in rats.

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:

PMID: 10100884 [PubMed - indexed for MEDLIN

 

53. 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:

PMID: 9862129 [PubMed - indexed for MEDLINE]

54.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]

54.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. bye01407@niftyserve.or.jp

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: PMID: 9669043 [PubMed - indexed for MEDLINE]

55.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 rats.

PMID: 9664842 [PubMed - indexed for MEDLINE]

56.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: PMID: 9644046 [PubMed - indexed for MEDLINE]

57.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]

58.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: PMID: 9550454 [PubMed - indexed for MEDLINE]

59.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: PMID: 9384567 [PubMed - indexed for MEDLINE]

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

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]

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61.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 fragments.

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 (1-->6)-beta-D-glucopyranosyl]-28-O-[beta-O-glucopyranosyl (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 activity.

Publication Types: PMID: 9433774 [PubMed - indexed for MEDLINE]

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

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: PMID: 9353896 [PubMed - indexed for MEDLINE]

63.Suppression of glucose absorption by extracts from the leaves of Gymnema inodorum.

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]

64.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 ands 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]

65.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: PMID: 9146906 [PubMed - indexed for MEDLINE]

66.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: PMID: 9087667 [PubMed - indexed for MEDLINE]

67.[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: PMID: 8985922 [PubMed - indexed for MEDLINE]

68.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]

69.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 (1-->3)-beta-D-glucuronopyranosyl]-gymnemanol, 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]

70.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: PMID: 8998848 [PubMed - indexed for MEDLINE]

71.Location of the disulfide bonds of the sweetness-suppressing polypeptide gurmarin.

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]

72.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.

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

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]

73.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]

74.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, Japan.

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]

75.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: PMID: 7787425 [PubMed - indexed for MEDLINE]

76.Gurmarin inhibition of sweet taste responses in mice.

Ninomiya Y, Imoto T.

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

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 receptor.

Publication Types: PMID: 7733384 [PubMed - indexed for MEDLINE]

77.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: PMID: 7734180 [PubMed - indexed for MEDLINE]

78.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 receptors.

Publication Types: PMID: 7800742 [PubMed - indexed for MEDLINE]

79.[Quantitative analysis of deacylgymnemic acid by high-performance liquid chromatography]

[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: PMID: 8492295 [PubMed - indexed for MEDLINE]

80.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: PMID: 1453221 [PubMed - indexed for MEDLINE]

81.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]

82.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]

83.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 proteins.

PMID: 1607357 [PubMed - indexed for MEDLINE]

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

Kurihara Y.

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

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: PMID: 1418601 [PubMed - indexed for MEDLINE]

85.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 hydrochloride.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types: PMID: 1653433 [PubMed - indexed for MEDLINE]

86.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]

87.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: PMID: 2259217 [PubMed - indexed for MEDLINE]

88.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: PMID: 2259216 [PubMed - indexed for MEDLINE]

89.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: PMID: 2259215 [PubMed - indexed for MEDLINE]

90.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, Japan.

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]

91.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: PMID: 3560992 [PubMed - indexed for MEDLINE]

92.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]

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

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 intake.

PMID: 6836034 [PubMed - indexed for MEDLINE]

94.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:  PMID: 479396 [PubMed - indexed for MEDLINE]

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