Beneficiary Effect of Tinospora cordifolia Against High-fructose Diet Induced Abnormalities in Carbohydrate and Lipid Metabolism in Wistar Rats

Abstract

High intake of dietary fructose has been shown to exert a number of adverse metabolic effects in humans and experimental animals. The present study was designed to investigate the effect of the aqueous extract of Tinospora cordifolia stem (TCAE) on the adverse effects of fructose loading toward carbohydrate and lipid metabolism in rats. Adult male Wistar rats of body weight around 200 g were divided into four groups, two of which were fed with starch diet and the other two with high fructose (66%) diet. Plant extract of TC (400 mg/kg/day) was administered orally to each group of the starch fed rats and the high-fructose fed rats. At the end of 60 days of experimental period, biochemical parameters related to carbohydrate and lipid metabolism were assayed. Hyperglycemia, hyperinsulinemia, hypertriglyceridemia, insulin resistance, and elevated levels of hepatic total lipids, cholesterol, triglycerides, and free fatty acids (p<0.05) observed in fructose-fed rats were completely prevented with TCAE treatment. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase) and lipid metabolism (fatty acid synthetase, lipoprotein lipase, and malic enzyme) as observed in the high fructose-fed rats were prevented with TCAE administration. In conclusion, our findings indicate improvement of glucose and lipid metabolism in high-fructose fed rats by treatment with Tinospora cordifolia, and suggest that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

Key words

insulin resistance - metabolic syndrome - diabetes mellitus - adipose tissue - medicinal plants - alternative medicines

References

• 1 Guzman-Maldonado H, Paredes-Lopez O. Amylolytic enzymes and products derived from starch: a review.  Crit Rev Food Sci Nutr. 1995;  35 373-403
• 2 Putnam JJ, Allshouse JE. Food consumption, prices, and expenditures, 1970–97. Washington, DC: Economic Research Service, US Department of Agriculture 1999
• 3 Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ. Fructose, weight gain, and the insulin resistance syndrome.  Am J Clin Nutr. 2002;  76 911-922
• 4 Tordoff MG, Alleva AM. Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight.  Am J Clin Nutr. 1990;  51 963-969
• 5 Schwarz J-M, Neese RA, Turner SM, Nguyen C, Hellerstein MK. Effect of fructose ingestion on glucose production (GP) and de novo lipogenesis (DNL) in normal and hyperinsulinemic obese humans.  Diabetes. 1994;  43 ((Suppl)) 52A
• 6 Thorburn AW, Storlein LH, Jemkins AB, Khouri S, Kraegen EW. Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats.  Am J Clin Nutr. 1989;  49 1155-1163
• 7 Reddy SS, Karuna R, Baskar R, Saralakumari D. Prevention of insulin resistance by ingesting aqueous extract of Ocimum sanctum to fructose-fed rats.  Horm Metab Res. 2008;  40 44-49
• 8 Beck-Nielsen H, Pedersen O, Lindskov HO. Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects.  Am J Clin Nutr. 1980;  33 273-278
• 9 Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats.  Hypertension. 1987;  10 512-516
• 10 Dills  Jr  WL. Protein fructosylation: fructose and the Mailard reaction.  Am J Clin Nutr. 1993;  58 779S-787S
• 11 Davail S, Rideau N, Bernadet MD, André JM, Guy G, Hoo-Paris R. Effects of dietary fructose on liver steatosis in overfed mule ducks.  Horm Metab Res. 2005;  37 32-35
• 12 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease.  Diabetes. 1988;  37 1595-1607
• 13 Faure P, Rossini E, Wiernsperger N, Richard MJ, Favier A, Halimi S. An insulin sensitizer improves the free radical defense system potential and insulin sensitivity in high fructose-fed rats.  Diabetes. 1999;  48 353-357
• 14 Verma S, Bhanot S, McNeill JH. Antihypertensive effects of metformin in fructose-fed hyperinsulinemic, hypertensive rats.  J Pharmacol Exp Ther. 1994;  271 1334-1347
• 15 Faure P, Rossini E, Lafond JL, Richard MJ, Favier A, Halimi S. Vitamin E improves the free radical defense system potential and insulin sensitivity of rats fed high fructose diets.  J Nutr. 1997;  127 103-107
• 16 Yagi N, Takasu N, Higa S, Ishikawa K, Murakami K, Mimura G. Effect of troglitazone, a new oral antidiabetic agent, on fructose-induced insulin resistance.  Horm Metab Res. 1995;  27 439-441
• 17 Hollenberg NK. Considerations for management of fluid dynamic issues associated with thiazolidinediones.  Am J Med. 2003;  115 S111-S115
• 18 Panchabhai TS, Kulkarni UP, Rege NN. Validation of therapeutic claims of Tinospora cordifolia: a review.  Phytother Res. 2008;  22 425-441
• 19 Singh SS, Pandey SC, Srivastava S, Gupta VS, Patro B, Gosh AC. Chemistry and medicinal properties of Tinospora cordifolia (guduchi).  Indian J Pharmacol. 2003;  35 83-91
• 20 Grover JK, Vats V, Rathi SS. Anti-hyperglycemic effect of Eugenia jambalona and Tinospora cordifolia in experimental diabetes and their effects on key metabolic enzymes involved in carbohydrate metabolism.  J Ethnopharmacol. 2000;  73 461-470
• 21 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin-phenol reagent.  J Biol Chem. 1951;  193 265-275
• 22 Singleton VL, Orthofer R, Lamuela-Raventós RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu Reagent.  Methods Enzymol. 1999;  299 152-178
• 23 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
• 24 Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues.  J Biol Chem. 1957;  226 497-597
• 25 Duncombe WG. The calorimetric micro-determination of long-chain fatty acids.  Biochem J. 1963;  88 7-10
• 26 Connerty HV, Briggs AR, Eaton  Jr  EH. Simplified determination of the lipid components of blood serum.  Clin Chem. 1961;  7 37-53
• 27 Carrol NV, Longley RW, Roe JH. The determination of glycogen in liver and muscle by use of anthrone reagent.  J Biol Chem. 1956;  220 583
• 28 Brandstrup N, Kirk JE, Bruni C. The hexokinase and phosphoglucoisomerase activities of aortic and pulmonary artery tissue in individuals of various ages.  J Gerontol. 1957;  12 166-171
• 29 Sadava D, Alonso D, Hong H, Barrett PD. Effect of Methadone addiction on glucose metabolism in rats.  General Pharmac. 1997;  28 27-29
• 30 King J. In: Practical Clinical Enzymology. London: Van Nostrand Co. 1965: 85-234
• 31 Sutherland EW. Polysaccharide phosphorylase, liver. In: Colowick SP, Kaplan NO (ed) Methods in Enzymol Vol 2. New York: Academic Press 1955: 215-218
• 32 Beutler E. In: Red cell metabolism, a manual of biochemical methods 2nd ed. New York: Grune and Stratton 1975: 66
• 33 Adelman RA, Spoiler PD, Weinhouse S. Dietary and hormonal regulation of enzymes of fructose metabolism in rat liver.  J Biol Chem. 1966;  241 5467
• 34 Geer BW, Krochko D, Oliver MJ, Walker VK, Williamson JH. A comparative study of the NADP- malic enzymes from Drosophila and chick liver.  Comp Biochem Physiol. 1980;  65B 25-34
• 35 Gibson DM, Hubbard DD. Incorporation of malonyl Co-A into fatty acids by liver in starvation and alloxan diabetes.  Biochem Bio-phys Res Commun. 1960;  3 531
• 36 Shirai K, Jackson RL. Lipoprotein lipase- catalyzed hydrolysis of p-nitrophenyl butyrate. Interfacial activation by phospholipid vesicles.  J Biol Chem. 1982;  257 1253-1258
• 37 Mayes PA. Intermediary metabolism of fructose.  Am J Clin Nutr. 1993;  58 ((Suppl)) 754S-765S
• 38 Parniak MA. Enhancement of glycogen concentrations in primary cultures of rat hepatocytes exposed to glucose and fructose.  Biochem J. 1988;  251 795-802
• 39 Hers HG, Stalmans W, de Wuif H, Laloux M, Hue L. The control of glycogen metabolism in the liver. In: Lundquist F, Tygstrup N (ed) Regulation of hepatic metabolism. Copenhagen: Munksgaard 1974: 237-249
• 40 Chevalier MM, Wiley JH, Leveille GA. Effect of dietary fructose on fatty acid synthesis in adipose tissue and liver of the rat.  J Nutr. 1972;  102 337-342
• 41 Prince PS, Menon VP, Gunasekaran G. Hypolipidaemic action of Tinospora cordifolia roots in alloxan diabetic rats.  J Ethnopharmacol. 1999;  64 53-57
• 42 Zhang W, Xu YC, Guo FJ, Meng Y, Li ML. Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus.  Chin Med J (Engl). 2008;  121 2124-2128
• 43 Turner N, Li JY, Gosby A, To SW, Cheng Z, Miyoshi H, Taketo MM, Coney GJ, Kraegen EW, James DE, Hu L-H, Li J, Ye J-M. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I.  Diabetes. 2008;  57 1414-1418
• 44 Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states.  Diabetes. 2006;  55 2256-2264
• 45 Kizelsztein P, Govorko D, Komarnytsky S, Evans A, Wang Z, Cefalu WT, Raskin I. 20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model.  Am J Physiol Endocrinol Metab. 2009;  296 E433-E439
• 46 Yoshida T, Otaka T, Uchiyama M, Ogawa S. Effect of ecdysterone on hyperglycemia in experimental animals.  Biochem Pharmacol. 1971;  20 3263-3268
• 47 Niu HS, Hsu FL, Liu IM, Cheng JT. Increase of beta-endorphin secretion by syringin, an active principle of Eleutherococcus senticosus, to produce antihyperglycemic action in type 1-like diabetic rats.  Horm Metab Res. 2007;  39 894-898
• 48 Rege NN, Thatte UM, Dahanukar SA. Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine.  Phytother Res. 1999;  13 275-291

Correspondence