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Gymnema

Scientific Name(s): Gymnema sylvestre (Retz.) Schult. Family: Asclepiadaceae (milkweed)

Common Name(s): Meshashringi , gurmar , merasingi , periploca of the woods

Uses

The plant has been used in traditional medicine, most notably to control blood glucose. Use as a lipid-lowering agent, for weight loss, and for the inhibition of caries have also been investigated, primarily in rodent studies. However, little to no clinical information is available to support the use of gymnema for any indication.

Dosing

Limited controlled studies exist. Clinical studies investigating antidiabetic effects have typically used 200 or 400 mg extract daily standardized to contain 25% gymnemic acids.

Contraindications

None established.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

A case report of hepatotoxicity exists.

Toxicology

Information is lacking.

Botany

G. sylvestre is a woody, climbing plant indigenous to the tropical forests of central and southern India. Distribution of gymnema is worldwide, and it is recognized in the traditional medicinal literature of many countries, including Australia, Japan, and Vietnam. The opposite, elliptic/ovate leaves are most commonly used, but the stem also appears to possess some pharmacologic activity. The plant bears small, yellowish flowers. Gymnema is also known as Asclepias geminata Roxb., Gymnema melicida Edg., and Pinus sylvestris Willd. Gymnema montanum has also been investigated. 1 , 2 , 3

History

Gymnema has played an important role in the traditional Ayurvedic medical system for centuries, primarily confined to the management of diabetes mellitus and similar hypo/hyperglycemic conditions. The leaves have also been used for stomach ailments, constipation, water retention, and liver disease. The flowers, leaves, and fruits have been used in the treatment of either high or low blood pressure, tachycardia, and arrhythmias. Chewing the leaves destroys the ability to discriminate sweet taste, giving it the common Hindi name of gurmar or “sugar destroyer.” The plant has been used alone and as a component of the Ayurvedic compound Tribang shila , a mixture of tin, lead, zinc, G. sylvestre leaves, neem ( Melia azadirachta ) leaves, Enicostemma littorale , and jambul ( Eugenia jambolana ) seeds. As early as 1930, the pharmacologic effect of the plant was investigated. The plant is available in a number of commercial over-the-counter herbal products. 3 , 4 , 5

Chemistry

Gymnemic acids, a group of triterpenoid saponins, are the main class of chemical constituents isolated from G. sylvestre and are thought to be responsible for the observed antidiabetic activity. The quantity of gymnemic acids extracted from the leaves varies according to the location of cultivation and the time of harvesting; concentrations varying between 0.67% and 1.06% have been reported. Multiple gymnemic acid congeners have been identified, and high performance liquid chromatography methods for standardization have been described.

Also present in gymnema extracts are gymnemasaponins, a group of antisweet principles with a novel D-glucoside structure. The structure of gurmarin, another antisweet agent found in gymnema, has been elucidated. Gymnemosides have been isolated from alcoholic extracts of G. sylvestre leaves. Other constituents include flavones, anthraquinones, chlorophylls, phytin, resins, quercitol, alkaloids, and tannic, formic, and butyric acids. 2 , 6 , 7 , 8 , 9 , 10 , 11

Uses and Pharmacology

Diabetes

Studies suggest the hypoglycemic effects of gymnema extracts operate through a number of possible mechanisms, including reduced uptake of glucose in the small intestine, improved glycolysis, glucogen synthesis and gluconeogenesis, and stimulation of insulin release from islets of Langerhans. 3 , 12 , 13 , 14

Animal data

A number of studies have evaluated the effects of G. sylvestre on blood sugar in animals, often in comparison with glibenclamide or tolbutamide. Most studies reported decreased blood glucose concentrations in diabetic rats. 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 Decreased lipid peroxidation and oxidative stress have also been demonstrated in rats. 21 , 23 , 24 , 25 , 26 In addition, taste response to sucrose, fructose, lactose, and maltose in rats was markedly suppressed by gurmarin, a protein extracted from G. sylvestre . 27 , 28

Clinical data

Few methodologically sound clinical studies exist. 3 , 29 Limited, small clinical studies found decreases in mean glycosylated hemoglobin (HbA 1c ), fasting blood glucose, and mean daily preprandial plasma glucose for patients with type 1 and 2 diabetes receiving gymnema extracts in addition to their usual medication. 30 , 31 , 32

Lipid-lowering
Animal data

A dose-dependent increase in fecal cholesterol and cholic acid-derived bile acid excretion has been demonstrated in rats. 33 A 3-week study showed a decrease in apparent fat digestibility and an increase in excretion of neutral sterols and acidic steroids in rats receiving an extract of G. sylvestre leaves and either a normal or high-fat diet. Total serum cholesterol and triglycerides were also decreased. 34 After 10 weeks, plasma triglycerides were lower in gymnema-fed rats compared with controls, but there was no difference in plasma total cholesterol levels. 35 In diabetic rats, improved lipid profiles were observed with gymnema extract and gymnemic triacetate. 36 , 37 , 38

Clinical data

Reduction in plasma cholesterol, triglycerides, and free fatty acid levels was observed in limited studies of diabetic patients who received supplements of gymnema in addition to their usual antidiabetic medication (eg, insulin, glibenclamide, tolbutamide). 30 , 31 Lipid lowering was a secondary end point in these studies, which were designed to demonstrate the antidiabetic effects of gymnema.

Weight loss
Animal data

Increases in body weight were suppressed in a long-term study of the administration of G. sylvestre extract to rats. 35 , 38 Conversely, in another rodent study, loss of weight was inhibited by gymnema extracts. 20

Clinical data

Decreased body weight has been demonstrated in studies using combinations of various dietary supplements, including G. sylvestre with chitosan, fenugreek, and vitamin C, and gymnema with niacin-chromium complex. The resultant weight loss cannot be attributed to a single ingredient. 39 , 40

Other uses
Antimicrobial

An alcoholic extract of dried leaves exhibited antibacterial activity against Bacillus pumilis , Bacillus subtilis , Pseudomonas aeruginosa , and Staphylococcus aureus . 41 Gymnemic acids A and B have demonstrated antiviral activity against the influenza virus. Other fractions lacked this activity. 6 A possible application in the prevention of dental plaque formation has been investigated, but systematic studies are lacking to confirm this use. 6

Anti-inflammatory

Histamine release from mast cells was inhibited by extracts of G. sylvestre in vitro. 6 Moderate inhibition of carrageenan-induced rat paw edema occurred with an aqueous extract of G. sylvestre leaves; naproxen produced superior inhibition of edema. However, efficacy of gymnema was similar to that of naproxen in a peritoneal ascites model in mice. Unlike naproxen, gymnema did not inhibit beneficial granuloma formation; gastric mucosa was not irritated by high doses. 42

Cancer

Radical scavenging and cytotoxic and antigenotoxic effects have been demonstrated for gymnema extracts, possibly due to phenolic and specific saponin content. 43 , 44 , 45

Ophthalmic

A combination product containing G. sylvestre extracts was protective against sugar-induced cataracts in rats. 46

Dosage

Clinical studies investigating antidiabetic effects have typically used 200 or 400 mg extract daily standardized to contain 25% gymnemic acids. 30 , 31 , 32 , 40

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. 32

Interactions

None well documented.

Adverse Reactions

A case report of reversible hepatotoxicity was attributed to the consumption of G. sylvestre as a tea. Toxicity was evident by laboratory indices and histology. 47 No adverse reactions were reported in 1 long-term clinical study. 30 Systolic blood pressure was raised in spontaneously hypertensive rats fed a high sucrose diet, but the clinical importance of this finding is unknown. 48

Toxicology

In a short-term toxicity study in mice, no gross behavioral, neurologic, or autonomic effects were observed. The acute median lethal dose (LD 50 ) was 3,990 mg/kg, and the safety ratio (LD 50 /median effective dose) was 11 and 16 in normal and diabetic rats, respectively. 18

Bibliography

1. Gymnema sylvestre (Retz.) Schult. USDA, NRCS. 2006. The PLANTS Database ( http://plants.usda.gov , 11 May 2011). National Plant Data Team, Greensboro, NC 27401-4901 USA.
2. Kanetkar P, Singhal R, Kamat M. Gymnema sylvestre : A Memoir. J Clin Biochem Nutr . 2007;41(2):77-81.
3. Leach MJ. Gymnema sylvestre for diabetes mellitus: a systematic review. J Altern Complement Med . 2007;13(9):977-983.
4. Mhaskar KS, Caius JF. A study of Indian medicinal plants. II. Gymnema sylvestre R . Br. Indian Med Res Memoirs . 1930;16:2-75.
5. Windholz M, ed. The Merck Index . 10th ed. Rahway, NJ: Merck & Co; 1983.
6. Porchezhian E, Dobriyal RM. An overview on the advances of Gymnema sylvestre : chemistry, pharmacology and patents. Pharmazie . 2003;58(1):5-12.
7. Fletcher JI, Dingley AJ, Smith R, Connor M, Christie MJ, King GF. High-resolution solution structure of gurmarin, a sweet-taste-suppressing plant polypeptide. Eur J Biochem . 1999;264(2):525-533.
8. Yoshikawa M, Murakami T, Kadoya M, et al. Medicinal foodstuffs. IX. The inhibitors of glucose absorption from the leaves of Gymnema sylvestre R.Br. (Asclepiadaceae): structures of gymnemosides a and b. Chem Pharm Bull . 1997;45(10):1671-1676.
9. Zhu XM, Xie P, Di YT, Peng SL, Ding LS, Wang MK. Two new triterpenoid saponins from Gymnema sylvestre . J Integr Plant Biol . 2008;50(5):589-592.
10. Puratchimani V, Jha S. Standardisation of Gymnema sylvestre r. Br. with reference to gymnemagenin by high-performance thin-layer chromatography. Phytochem Anal . 2004;15(3):164-166.
11. Raju VS, Kannababu S, Subbaraju GV. Standardisation of Gymnema sylvestre R.Br. by high-performance thin-layer chromatography: an improved method. Phytochem Anal . 2006;17(3):192-196.
12. Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinol . 1999;163(2):207-212.
13. Shimizu K, Iino A, Nakajima J, et al. Suppression of glucose absorption by some fractions extracted from Gymnema sylvestre leaves. J Vet Med Sci . 1997;59(4):245-251.
14. Liu B, Asare-Anane H, Al-Romaiyan A, et al. Characterisation of the insulinotropic activity of an aqueous extract of Gymnema sylvestre in mouse beta-cells and human islets of Langerhans. Cell Physiol Biochem . 2009;23(1-3):125-132.
15. Rahman AU, Zaman K. Medicinal plants with hyphoglycemic activity. J Ethnopharmacol . 1989;26(1):1-55.
16. Gupta SS, Seth CB. Experimental studies on pituitary diabetes. II. Comparison of blood sugar level in normal and anterior pituitary extract induced hyperglycemic rats treated with a few Ayurvedic remedies. Indian J Med Res . 1962;50:708-714.
17. Gupta SS, Variyar MC. Experimental studies on pituitary diabetes. IV. Effect of Gymnema sylvestre and Coccinia indica against the hyperglycaemic response of somatotropin and corticotropin hormones. Indian J Med Res . 1964;52:200-207.
18. Chattopadhyay RR. A comparative evaluation of some blood sugar lowering agents of plant origin. J Ethnopharmacol . 1999;67(3):367-372.
19. Gholap S, Kar A. Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones. Pharmazie . 2003;58(6):413-415.
20. Ramkumar KM, Ponmanickam P, Velayuthaprabhu S, Archunan G, Rajaguru P. Protective effect of Gymnema montanum against renal damage in experimental diabetic rats. Food Chem Toxicol . 2009;47(10):2516-2521.
21. Ramkumar KM, Rajaguru P, Latha M, Ananthan R. Effect of Gymnema montanum leaves on red blood cell resistance to oxidative stress in experimental diabetes. Cell Biol Toxicol . 2008;24(3):233-241.
22. Yadav M, Lavania A, Tomar R, Prasad GB, Jain S, Yadav H. Complementary and comparative study on hypoglycemic and antihyperglycemic activity of various extracts of Eugenia jambolana seed, Momordica charantia fruits, Gymnema sylvestre , and Trigonella foenum graecum seeds in rats. Appl Biochem Biotechnol . 2010;160(8):2388-2400.
23. Ananthan R, Latha M, Ramkumar KM, Pari L, Baskar C, Narmatha Bai V. Modulatory effects of Gymnema montanum leaf extract on alloxan-induced oxidative stress in Wistar rats. Nutrition . 2004;20(3):280-285.
24. Ramkumar KM, Latha M, Venkateswaran S, Pari L, Ananthan R, Bai VN. Modulatory effect of Gymnema montanum leaf extract on brain antioxidant status and lipid peroxidation in diabetic rats. J Med Food . 2004;7(3):366-371.
25. Ramkumar KM, Manjula C, Sankar L, Suriyanarayanan S, Rajaguru P. Potential in vitro antioxidant and protective effects of Gymnema montanum H . on alloxan-induced oxidative damage in pancreatic beta-cells, HIT-T15. Food Chem Toxicol . 2009;47(9):2246-2256.
26. Ramkumar KM, Lee AS, Krishnamurthi K, et al. Gymnema montanum H . protects against alloxan-induced oxidative stress and apoptosis in pancreatic beta-cells. Cell Physiol Biochem . 2009;24(5-6):429-440.
27. Katsukawa H, Imoto T, Ninomiya Y. Induction of salivary gumarin-binding proteins in rats fed gymnema-containing diets. Chem Senses . 1999;24(4):387-392.
28. Harada S, Kasahara Y. Inhibitory effect of gurmarin on palatal taste responses to amino acids in the rat. Am J Physiol Regul Integr Comp Physiol . 2000;278(6):R1513-R1517.
29. Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care . 2003;26(4):1277-1294.
30. Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol . 1990;30(3):281-294.
31. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol . 1990;30(3):295-300.
32. Joffe DJ, Freed SH. Effect of extended release Gymnema sylvestre leaf extract ( Beta Fast G-XR ) alone or in combination with oral hypoglycemics or insulin regimens for type 1 and type 2 diabetes. Diabetes in Control Newsletter . 2001;76(1).
33. Nakamura Y, Tsumura Y, Tonogai Y, Shibata T. Fecal steroid excretion is increased in rats by oral administration of gymnemic acids contained in Gymnema sylvestre leaves. J Nutr . 1999;129(6):1214-1222.
34. Shigematsu N, Asano R, Shimosaka M, Okazaki M. Effect of administration with the extract of Gymnema sylvestre R.Br leaves on lipid metabolism in rats. Biol Pharm Bull . 2001;24(6):713-717.
35. Shigematsu N, Asano R, Shimosaka M, Okazaki M. Effect of long-term administration with Gymnema sylvestre R. Br on plasma and liver lipid in rats. Biol Pharm Bull . 2001;24(6):643-649.
36. Ramkumar KM, Vijayakumar RS, Ponmanickam P, Velayuthaprabhu S, Archunan G, Rajaguru P. Antihyperlipidaemic effect of Gymnema montanum : a study on lipid profile and fatty acid composition in experimental diabetes. Basic Clin Pharmacol Toxicol . 2008;103(6):538-545.
37. Daisy P, Eliza J, Mohamed Farook KA. A novel dihydroxy gymnemic triacetate isolated from Gymnema sylvestre possessing normoglycemic and hypolipidemic activity on STZ-induced diabetic rats. J Ethnopharmacol . 2009;126(2):339-344.
38. Luo H, Kashiwagi A, Shibahara T, Yamada K. Decreased bodyweight without rebound and regulated lipoprotein metabolism by gymnemate in genetic multifactor syndrome animal. Mol Cell Biochem . 2007;299(1-2):93-98.
39. Woodgate DE, Conquer JA. Effects of a stimulant-free dietary supplement on body weight and fat loss in obese adults: a six-week exploratory study. Curr Ther Res . 2003;64(4):248-262.
40. Preuss HG, Bagchi D, Bagchi M, Rao CV, Dey DK, Satyanarayana S. 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. Diabetes Obes Metab . 2004;6(3):171-180.
41. Satdive RK, Abhilash P, Fulzele DP. Antimicrobial activity of Gymnema sylvestre leaf extract. Fitoterapia . 2003;74(7-8):699-701.
42. Diwan PV, Margaret I, Ramakrishna S. Influence of Gymnema sylvestre on inflammation. Inflammopharmacology . 1995;3(3):271-277.
43. Ramkumar KM, Sankar L, Manjula C, et al. Antigenotoxic potential of Gymnema montanum leaves on DNA damage in human peripheral blood lymphocytes and HL-60 cell line. Environ Mol Mutagen . 2010;51(4):285-293.
44. Ohmori R, Iwamoto T, Tago M, et al. Antioxidant activity of various teas against free radicals and LDL oxidation. Lipids . 2005;40(8):849-853.
45. Khanna VG, Kannabiran K. Anticancer-cytotoxic activity of saponins isolated from the leaves of Gymnema sylvestre and Eclipta prostrata on HeLa cells. Int J Green Pharm . 2009;3(3):227-229.
46. Moghaddam MS, Kumar PA, Reddy GB, Ghole VS. Effect of Diabecon on sugar-induced lens opacity in organ culture: mechanism of action. J Ethnopharmacol . 2005;97(2):397-403.
47. Shiyovich A, Sztarkier I, Nesher L. Toxic hepatitis induced by Gymnema sylvestre , a natural remedy for type 2 diabetes mellitus. Am J Med Sci . 2010;340(6):514-517.
48. P reuss HG, Jarrell ST, Scheckenbach R, Lieberman S, Anderson RA. Comparative effects of chromium, vanadium and Gymnema sylvestre on sugar-induced blood pressure elevations in SHR. J Am Coll Nutr . 1998;17(2):116-123.

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