Medicinal Chemistry Research

, Volume 19, Issue 8, pp 948–961 | Cite as

Inhibitory effect of Gymnema Montanum leaves on α-glucosidase activity and α-amylase activity and their relationship with polyphenolic content

  • Kunga Mohan Ramkumar
  • Balsamy Thayumanavan
  • Thayumanavan Palvannan
  • Palanisamy Rajaguru
Original Research


The present study was attempted to investigate the effect of G. montanum leaf extract on inhibition of α-glucosidase and α-amylase activity. The ethanol extract of G. montanum (GLEt) at various concentrations (1–10 μg/ml) was tested for its inhibition pattern against α-glucosidase and α-amylase activity in vitro and compared with the commercially available α-glucosidase inhibitor, acarbose. The GLEt showed competitive inhibition against yeast α-glucosidase and noncompetitive inhibition against salivary α-amylase in a concentration-dependent manner. Further, we investigated the effect of extract on levels of blood glucose and plasma insulin in neonatal streptozotocin-induced type 2 diabetic rats. Long-term administration (12 weeks) of the GLEt effectively reduced the blood glucose level and also increased the insulin level. In a preliminary phytochemical analysis, G. montanum leaves were rich in phenolic composition and found to be positively correlated with the inhibitory effect of α-glucosidase and α-amylase activity. These results suggest that the GLEt might exert its antidiabetic effect by suppressing carbohydrate absorption from the intestine and thereby reducing hyperglycemia.


α-Glucosidase inhibitor α-Amylase inhibitor Gymnema montanum Type 2 diabetes nSTZ rats Medicinal plants 


  1. Ananthan R, Latha M, Pari L, Ramkumar KM, Baskar CG, Bai VN (2003a) Effect of Gymnema montanum on blood glucose, plasma insulin, and carbohydrate metabolic enzymes in alloxan-induced diabetic rats. J Med Food 6(1):43–49CrossRefPubMedGoogle Scholar
  2. Ananthan R, Latha M, Ramkumar KM, Pari L, Baskar CG, Bai VN (2003b) Effect of Gymnema montanum leaves on serum and tissue lipids in alloxan diabetic rats. Exp Diabesity Res 4(3):183–189PubMedGoogle Scholar
  3. Andrade-Cetto A, Becerra-Jimenez J, Cardenas-Vazquez R (2008) Alfa-glucosidase-inhibiting activity of some Mexican plants used in the treatment of type 2 diabetes. J Ethnopharmacol 116(1):27–32CrossRefPubMedGoogle Scholar
  4. Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL (2004) Neonatal streptozotocin-induced rat model of Type 2 diabetes mellitus: a glance. Ind J Pharmacol 6(4):217–221Google Scholar
  5. Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER (1990) Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 30(3):295–300CrossRefPubMedGoogle Scholar
  6. Bergmeyer HU, Bernt E (1974) Methods of enzymatic analysis, 2nd edn. Academic Press, New York, pp 1205–1215Google Scholar
  7. Bhat M, Zinjarde SS, Bhargava SY, Kumar AR, Joshi BN (2008) Antidiabetic Indian plants: a good source of potent amylase inhibitors. eCAM Advance Access published on June 27, 2008. doi:10.1093/ecam/nen040
  8. Bollen M, Stalmans W (1989) The antiglycogenolytic action of 1-deoxynojirimycin results from a specific inhibition of the α-1,6-glucosidase activity of the debranching enzyme. Eur J Biochem 181:775–780CrossRefPubMedGoogle Scholar
  9. Bonner Weir S, Trent DF, Honey RN, Weir GC (1981) Response of neonatal rat islets to streptozotocin. Limited β-cell regeneration and hyperglycemia. Diabetes 30:64–69CrossRefPubMedGoogle Scholar
  10. Breuer HW (2003) Review of acarbose therapeutic strategies in the long-term treatment and in the prevention of type 2 diabetes. Int J Clin Pharmacol Ther 41(10):421–440PubMedGoogle Scholar
  11. Burits M, Bucar F (2000) Antioxidant activity of Nigella sativa essential oil. Phytother Res 14(5):323–328CrossRefPubMedGoogle Scholar
  12. Carrascosa JM, Molero JC, Fermin Y, Martinez C, Andres A, Satrustegui J (2001) Effects of chronic treatment with acarbose on glucose and lipid metabolism in obese diabetic Wistar rats. Diabetes Obes Metab 3(4):240–248CrossRefPubMedGoogle Scholar
  13. Chakrabarti R, Rajagopalan R (2002) Diabetes and insulin resistance associated disorders: disease and the therapy. Curr Sci 83(12):1533–1538Google Scholar
  14. Chattopadhyay RR (1998) Possible mechanism of antihyperglycemic effect of Gymnema sylvestre leaf extract, part I. Gen Pharmacol 31(3):495–496CrossRefPubMedGoogle Scholar
  15. Chiba S (1997) Molecular mechanism in alpha-glucosidase and glucoamylase. Biosci Biotechnol Biochem 61(8):1233–1239CrossRefPubMedGoogle Scholar
  16. Djeridane A, Yousfi M, Nadjemi B, Boutassouna D, Stocher P, Vidal N (2006) Antioxidant activity of some Algerian medicinal plants extracts containing phenolic compounds. Food Chem 97:654–660CrossRefGoogle Scholar
  17. Gowri PM, Tiwari AK, Ali AZ, Rao JM (2007) Inhibition of alpha-glucosidase and amylase by bartogenic acid isolated from Barringtonia racemosa Roxb. seeds. Phytother Res 21(8):796–799CrossRefPubMedGoogle Scholar
  18. Hirata S, Abe T, Imoto T (1992) Effects of crude gymnemic acid on the oral glucose tolerance test in the human being. J Yonago Med Assoc 43:392–396Google Scholar
  19. Hosoyama H, Sugimoto A, Suzuki Y, Sakane I, Kakuda T (2003) Isolation and qualitative analysis of the alpha-amylase inhibitor in Lagerstroemia speciosa (L.) Pers. (Banaba). Yakugushiu Zasshi 123:599–605CrossRefGoogle Scholar
  20. Imoto T, Yamamoto FM, Miyasaka A, Hatano H (1991) High-performance liquid chromatography atmospheric pressure ionization mass spectrometry of gymnemic acids. J Chromatogr 557:383–389CrossRefGoogle Scholar
  21. Inzucchi SE (2002) Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 287(3):360–372CrossRefPubMedGoogle Scholar
  22. Kim YM, Jeong YK, Wang MH, Lee WY, Rhee HI (2005) Inhibitory effect of pine extract on alpha-glucosidase activity and postprandial hyperglycemia. Nutrition 21(6):756–761CrossRefPubMedGoogle Scholar
  23. Kimura I (2006) Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions. Yakugaku Zasshi 126(3):133–143CrossRefPubMedGoogle Scholar
  24. King H, Aubert RE, Herman WH (1998) Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 21(9):1414–1431CrossRefPubMedGoogle Scholar
  25. Kumarappan C, Mandal SC (2008) α-Glucosidase inhibitory activity and in vitro antioxidant activities of alcohol-water extract (AWE) of Ichnocarpus frutescens leaves. Med Chem Res 17:219–233CrossRefGoogle Scholar
  26. Leach MJ (2007) Gymnema sylvestre for diabetes mellitus:a systematic review. J Altern Complement Med 13(9):977–983CrossRefPubMedGoogle Scholar
  27. Lee HW, Park YS, Choi JW, Yi SY, Shin WS (2003) Antidiabetic effects of chitosan oligosaccharides in neonatal streptozotocin-induced noninsulin-dependent diabetes mellitus in rats. Biol Pharm Bull 26(8):1100–1103CrossRefPubMedGoogle Scholar
  28. Luo H, Imoto T, Hiji Y (2001a) Inhibitory effect of voglibose and gymnemic acid on maltose absorption in vivo. World J Gastroenterol 7(2):270–274PubMedGoogle Scholar
  29. Luo H, Wang LF, Imoto T, Hiji Y (2001b) Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine. World J Gastroenterol 7(1):9–15PubMedGoogle Scholar
  30. Maeda K, Kakabayashi S, Matsubara H (1985) Complete amino acid sequence of an alpha-amylase inhibitor in wheat kernel (019-inhibitor). Biochim Biophys Acta 828(3):213–221PubMedGoogle Scholar
  31. Mai TT, Thu NN, Tien PG, Van Chuyen N (2007) Alpha-glucosidase inhibitory and antioxidant activities of Vietnamese edible plants and their relationships with polyphenol contents. J Nutr Sci Vitaminol (Tokyo) 53(3):267–276CrossRefGoogle Scholar
  32. Matsui T, Ueda T, Oki T, Sugita K, Terahara N, Matsumoto K (2001) Alpha-glucosidase inhibitory action of natural acylated anthocyanins. 1. Survey of natural pigments with potent inhibitory activity. J Agr Food Chem 49(4):1948–1951CrossRefGoogle Scholar
  33. Matsui T, Ebuchi S, Kobayashi M, Fukui K, Sugita K, Terahara N (2002) Anti-hyperglycemic effect of diacylated anthocyanin from Ipomea batatas cultivar Ayamurasaki can be achieved by through the α-glucosidase inhibitory action. J Agr Food Chem 50:7244–7248CrossRefGoogle Scholar
  34. Matsui T, Ogunwande IA, Abesundara KJ, Matsumoto K (2006) Anti-hyperglycemic potential of natural products. Mini Rev Med Chem 6(3):349–356CrossRefPubMedGoogle Scholar
  35. McDougall GJ, Shpiro F, Dobson P, Smith P, Blake A, Stewart D (2005) Different polyphenolic components of soft fruits inhibit alpha-amylase and alpha-glucosidase. J Agr Food Chem 53(7):2760–2766CrossRefGoogle Scholar
  36. Ortiz-Andrade RR, Garcia-Jimenez S, Castillo-Espana P, Ramirez-Avila G, Villalobos-Molina R, Estrada-Soto S (2007) Alpha-glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent. J Ethnopharmacol 109(1):48–53CrossRefPubMedGoogle Scholar
  37. Persaud SJ, Al-Majed H, Raman A, Jones PM (1999) Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinol 163(2):207–212CrossRefPubMedGoogle Scholar
  38. Ramkumar KM, Latha M, Ashokkumar N, Pari L, Ananthan R (2005) Modulation of impaired cholinesterase activity in experimental diabetes: effect of Gymnema montanum leaf extract. J Basic Clin Physiol Pharmacol 16(1):17–35PubMedGoogle Scholar
  39. Ramkumar KM, Rajaguru P, Latha M, Ananthan R (2007a) Ethanol extract of Gymnema montanum leaves reduces glycoprotein components in experimental diabetes. Nutr Res 27(2):97–103CrossRefGoogle Scholar
  40. Ramkumar KM, Rajaguru P, Latha M, Ananthan R (2007b) Amelioration of metabolic complications associated with diabetes by Gymnema montanum in alloxan induced rats. In: Govil JN, Singh VK, Siddiqui NT (eds) Recent progress in medicinal plants, vol 18. Studium Press, Austin, pp 319–338Google Scholar
  41. Ramkumar KM, Rajaguru P, Ananthan R (2007c) Antimicrobial properties and phytochemical constituents of an antidiabetic plant Gymnema montanum. Adv Biol Res 1(1–2):67–71Google Scholar
  42. Ramkumar KM, Rajaguru P, Latha M, Ananthan R (2008a) Effect of Gymnema montanum leaves on red blood cell resistance to oxidative stress in experimental diabetes. Cell Biol Toxicol 24(3):233–241CrossRefPubMedGoogle Scholar
  43. Ramkumar KM, Vijayakumar RS, Ponmanickam P, Velayuthaprabhu S, Archunan G, Rajaguru P (2008b) Antihyperlipidaemic effect of Gymnema montanum: a study on lipid profile and fatty acid composition in experimental diabetes. Basic Clin Pharmacol Toxicol 103(6):538–545CrossRefPubMedGoogle Scholar
  44. Ramkumar KM, Manjula C, Sankar L, Suriyanarayanan S, Rajaguru P (2009) 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 47(9):2246–2256CrossRefPubMedGoogle Scholar
  45. Scheen AJ (2003) Is there a role for α-glucosidase inhibitors in the prevention of type 2 diabetes mellitus? Drugs 10:933–951CrossRefGoogle Scholar
  46. Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B (1990) Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol 30(3):281–294CrossRefPubMedGoogle Scholar
  47. Shimizu K, Ozeki M, Iino A, Nakajyo S, Urakawa N, Atsuchi M (2001) Structure-activity relationships of triterpenoid derivatives extracted from Gymnema inodorum leaves on glucose absorption. Jpn J Pharmacol 86(2):223–229CrossRefPubMedGoogle Scholar
  48. Shinde J, Taldone T, Barletta M, Kunaparaju N, Hu B, Kumar S, Placido J, Zito SW (2008) Alpha-glucosidase inhibitory activity of Syzygium cumini (Linn.) Skeels seed kernel in vitro and in Goto-Kakizaki (GK) rats. Carbohydr Res 343(7):1278–1281CrossRefPubMedGoogle Scholar
  49. Sima AA, Chakrabarti S (1992) Long-term suppression of postprandial hyperglycaemia with acarbose retards the development of neuropathies in the BB/W-rat. Diabetologia 35(4):325–330CrossRefPubMedGoogle Scholar
  50. Sugihara Y, Nojima H, Matsuda H, Murakami T, Yoshikawa M, Kimura I (2000) Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice. J Asian Nat Prod Res 2(4):321–327CrossRefPubMedGoogle Scholar
  51. Sundaram PV, Hill PG (1992) Glucose oxidase impette-serum glucose estimation. Ann NY Acad Sci 672:608–612CrossRefGoogle Scholar
  52. Tadera K, Minami Y, Takamatsu K, Matsuoka T (2006) Inhibition of alpha-glucosidase and alpha-amylase by flavonoids. J Nutr Sci Vitaminol (Tokyo) 52(2):149–153CrossRefGoogle Scholar
  53. Tiwari AK, Madhusudana Rao J (2002) Diabetes mellitus and multiple therapeutic approaches of phytochemicals: present status and future prospects. Curr Sci 83(1):30–38Google Scholar
  54. Toeller M (1994) Alpha-glucosidase inhibitors in diabetes: efficacy in NIDDM subjects. Eur J Clin Invest 24(3):31–35CrossRefPubMedGoogle Scholar
  55. van de Laar FA, Lucassen PL, Akkermans RP, van de Lisdonk EH, Rutten GE, van Weel C (2005) Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care 28(1):154–163CrossRefPubMedGoogle Scholar
  56. Xie JT, Wang A, Mehendale S, Wu J, Aung HH, Dey L, Qiu S, Yuan CS (2003) Anti-diabetic effects of Gymnema yunnanense extract. Pharmacol Res 47(4):323–329CrossRefPubMedGoogle Scholar
  57. Yoshikawa M, Nishida N, Shimoda H, Takada M, Kawahara Y, Matsuda H (2001) Polyphenol constituents from Salacia species: quantitative analysis of mangiferin with alpha-glucosidase and aldose reductase inhibitory activities. Yakugaku Zasshi 121(5):371–378CrossRefPubMedGoogle Scholar
  58. Yoshioka S (1986) Inhibitory effects of gymnemic acid and an extract from the leaves of Zizyphus jujuba on glucose absorption in the rat small intestine. J Yonago Med Assoc 37:142–145Google Scholar
  59. Youn JY, Park HY, Cho KH (2004) Anti-hyperglycemic activity of Commelina communis L.: inhibition of alpha-glucosidase. Diabetes Res Clin Pract 66(1):S149–S155CrossRefPubMedGoogle Scholar

Copyright information

© Birkhäuser Boston 2009

Authors and Affiliations

  • Kunga Mohan Ramkumar
    • 1
  • Balsamy Thayumanavan
    • 2
  • Thayumanavan Palvannan
    • 3
  • Palanisamy Rajaguru
    • 1
  1. 1.Department of BiotechnologyAnna University TiruchirappalliTiruchirappalliIndia
  2. 2.Department of Biochemistry, Centre for Plant Molecular BiologyTamilnadu Agricultural UniversityCoimbatoreIndia
  3. 3.Department of BiochemistryPeriyar UniversitySalemIndia

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