Abstract
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.
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References
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):43–49
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):183–189
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):27–32
Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL (2004) Neonatal streptozotocin-induced rat model of Type 2 diabetes mellitus: a glance. Ind J Pharmacol 6(4):217–221
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):295–300
Bergmeyer HU, Bernt E (1974) Methods of enzymatic analysis, 2nd edn. Academic Press, New York, pp 1205–1215
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
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 181:775–780
Bonner Weir S, Trent DF, Honey RN, Weir GC (1981) Response of neonatal rat islets to streptozotocin. Limited β-cell regeneration and hyperglycemia. Diabetes 30:64–69
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):421–440
Burits M, Bucar F (2000) Antioxidant activity of Nigella sativa essential oil. Phytother Res 14(5):323–328
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):240–248
Chakrabarti R, Rajagopalan R (2002) Diabetes and insulin resistance associated disorders: disease and the therapy. Curr Sci 83(12):1533–1538
Chattopadhyay RR (1998) Possible mechanism of antihyperglycemic effect of Gymnema sylvestre leaf extract, part I. Gen Pharmacol 31(3):495–496
Chiba S (1997) Molecular mechanism in alpha-glucosidase and glucoamylase. Biosci Biotechnol Biochem 61(8):1233–1239
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 97:654–660
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):796–799
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 43:392–396
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 123:599–605
Imoto T, Yamamoto FM, Miyasaka A, Hatano H (1991) High-performance liquid chromatography atmospheric pressure ionization mass spectrometry of gymnemic acids. J Chromatogr 557:383–389
Inzucchi SE (2002) Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 287(3):360–372
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):756–761
Kimura I (2006) Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions. Yakugaku Zasshi 126(3):133–143
King H, Aubert RE, Herman WH (1998) Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 21(9):1414–1431
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 17:219–233
Leach MJ (2007) Gymnema sylvestre for diabetes mellitus:a systematic review. J Altern Complement Med 13(9):977–983
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):1100–1103
Luo H, Imoto T, Hiji Y (2001a) Inhibitory effect of voglibose and gymnemic acid on maltose absorption in vivo. World J Gastroenterol 7(2):270–274
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):9–15
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):213–221
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):267–276
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):1948–1951
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 50:7244–7248
Matsui T, Ogunwande IA, Abesundara KJ, Matsumoto K (2006) Anti-hyperglycemic potential of natural products. Mini Rev Med Chem 6(3):349–356
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):2760–2766
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):48–53
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):207–212
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):17–35
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):97–103
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 319–338
Ramkumar KM, Rajaguru P, Ananthan R (2007c) Antimicrobial properties and phytochemical constituents of an antidiabetic plant Gymnema montanum. Adv Biol Res 1(1–2):67–71
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):233–241
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):538–545
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):2246–2256
Scheen AJ (2003) Is there a role for α-glucosidase inhibitors in the prevention of type 2 diabetes mellitus? Drugs 10:933–951
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):281–294
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):223–229
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):1278–1281
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):325–330
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):321–327
Sundaram PV, Hill PG (1992) Glucose oxidase impette-serum glucose estimation. Ann NY Acad Sci 672:608–612
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):149–153
Tiwari AK, Madhusudana Rao J (2002) Diabetes mellitus and multiple therapeutic approaches of phytochemicals: present status and future prospects. Curr Sci 83(1):30–38
Toeller M (1994) Alpha-glucosidase inhibitors in diabetes: efficacy in NIDDM subjects. Eur J Clin Invest 24(3):31–35
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):154–163
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):323–329
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):371–378
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 37:142–145
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–S155
Acknowledgment
K. M. Ramkumar is grateful to the Council of Scientific and Industrial Research, New Delhi, for awarding him a Senior Research Fellowship.
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Ramkumar, K.M., Thayumanavan, B., Palvannan, T. et al. Inhibitory effect of Gymnema Montanum leaves on α-glucosidase activity and α-amylase activity and their relationship with polyphenolic content. Med Chem Res 19, 948–961 (2010). https://doi.org/10.1007/s00044-009-9241-5
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DOI: https://doi.org/10.1007/s00044-009-9241-5