PREVENTION OF OBESITY AND DEVELOPMENT OF METABOLIC SYNDROME BY MANGOSTEEN (GARCINIA MANGOSTANA L.) PERICARP ETHANOLIC EXTRACT IN MALE WISTAR RATS FED WITH HIGH-FAT DIET
Keywords:Garcinia mangostana, obesity, fatty liver, insulin resistance, resistin, adiponectin, leptin
Objective: This study was conducted to evaluate the mangosteen (Garcinia mangostana) pericarp ethanolic extract (MPEE) properties in preventing obesity as well as its associated metabolic syndrome by analyzing the liver histology and measuring resistin, leptin, and adiponectin in the rats fed high-fat diet.
Methods: The experimental study with male Wistar rats was conducted for 9 w, with rats divided into 5 treatment groups which were normal (standard diet), control (high-fat diet), dose 1 (high-fat diet, MPEE 200 mg/kg b.w.), dose 2 (high-fat diet, MPEE 500 mg/kg b.w.), and orlistat (high-fat diet, orlistat 21.6 mg/kg b.w.) groups. The fat and liver index were calculated at the last day of the experiment. The liver was collected for the histology analysis while the serum was collected for quantification of resistin, leptin, and adiponectin level by enzyme-linked immunosorbent assay (ELISA) method.
Results: MPEE significantly reduced the liver index and total fat index compared to the control group. The rats treated with MPEE have the better liver condition than untreated rats, showed by lower histopathological score and lipid droplets, as well as higher percentage of functional cytoplasm. The MPEE also able to reduce the resistin and leptin level in high-fat diet rats, and slightly increase the adiponectin level. MPEE have better activities in all parameter compared to commercially available anti-obesity drug orlistat.
Conclusion: The mangosteen pericarp ethanolic extract (MPEE) has high potential as anti-obesity drugs, clinical and toxicology studies should be pursued for further application to human.
Keywords: Garcinia mangostana, Obesity, Fatty liver, Insulin resistance, Resistin, Adiponectin, Leptin
Pedraza-ChaverrÃ J, CÃ¡rdenas-RodrÃguez N, Orozco-Ibarra M, PÃ©rez-Rojas JM. Medicinal properties of mangosteen (Garcinia mangostana). Food Chem Toxicol 2008;46:3227-39.
Akao Y, Nakagawa Y, Iinuma M, Nozawa Y. Anti-cancer effects of xanthones from pericarps of mangosteen. Int J Mol Sci 2008;9:355-70.
Cui J, Hu W, Cai Z, Liu Y, Li S, Tao W, et al. New medicinal properties of mangostins: Analgesic activity and pharmacological characterization of active ingredients from the fruit hull of Garcinia mangostana L. Pharmacol Biochem Behav 2010;95:166-72.
Liu Q, Wang Y, Lin L. New insights into the anti-obesity activity of xanthones from Garcinia mangostana. Food Funct 2015;6:383-93.
Bray GA. Obesity: the disease. J Med Chem 2006;49:4001-7.
Bunkrongcheap R, Hutadilok-Towatana N, Noipha K, Wattanapiromsakul C, Inafuku M, Oku H. Ivy gourd (Coccinia grandis L. Voigt) root suppresses adipocyte differentiation in 3T3-L1 cells. Lipids Health Dis 2014;13:88.
Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes 2008;32:1431-7.
Seidell JC, Halberstadt J. The global burden of obesity and the challenges of prevention. Ann Nutr Metab 2015;66:7-12.
Devalaraja S, Jain S, Yadav H. Exotic fruits as therapeutic complements for diabetes, obesity, and metabolic syndrome. Food Res Int 2011;44:1856-65.
Silha J, Krsek M, Skrha JV, Sucharda P, Nyomba BIG, Murphy LJ. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003;149:331-5.
Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature 2001;409:307-12.
Vendrell J, Broch M, Vilarrasa N, Molina A, Gomez JM, Gutierrez C, et al. Resistin, Adiponectin, Ghrelin, Leptin, and proinflammatory cytokines: relationships in obesity. Obes Res 2004;12:962-71.
Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptinâ€”the classical, resistinâ€”the controversial, adiponectinâ€”the promising, and more to come. Best Pract Res Clin Endocrinol Metab 2005;19:525-46.
Udani JK, Singh BB, Barrett ML, Singh VJ. Evaluation of mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding the study. Nutr J 2009;8:48.
Taher M, Amiroudine MZAM, Zakaria TMFST, Susanti D, Ichwan SJA, Kaderi MA, et al. Î±-Mangostin improves glucose uptake and inhibits adipocytes differentiation in 3T3-L1 Cells via PPARÎ³, GLUT4, and leptin expressions. J Evidence-Based Complementary Altern Med 2015;1-9. Doi.org/10.1155/ 2015/740238. [Article in Press]
Li P, Tian W, Ma X. Alpha-mangostin inhibits intracellular fatty acid synthase and induces apoptosis in breast cancer cells. Mol Cancer 2014;13:138.
Shibata M, Iinuma M, Morimoto J, Kurose H, Akamatsu K, Okuno Y, et al. Î±-Mangostin extracted from the pericarp of the mangosteen (Garcinia mangostana Linn) reduces tumor growth and lymph node metastasis in an immunocompetent xenograft model of metastatic mammary cancer carrying a p53 mutation. BMC Med 2011;9:1-18.
Adnyana IK, Elin YS, Ary Y, Finna S. Anti-obesity effect of the pomegranate leaves ethanol extract (Punica granatum L.) in high-fat diet induced mice. Int J Pharm Sci 2014;6:626-31.
Brunt EM, Tiniakos DG. Histopathology of nonalcoholic fatty liver disease. World J Gastroenterol 2010;16:5286-96.
Cipriani S, Mencarelli A, Palladino G, Fiorucci S. FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats. J Lipid Res 2010;51:771-84.
Lois K, Kumar S. Obesity and diabetes. Endocrinol Nutr 2009;4:38-42.
Stern JS, Peerson J, Mishra AT, Rao MVS, Rajeswari KP. Efficacy and tolerability of a novel herbal formulation for weight management. Obesity 2013;21:921-7.
Jung H, Kim Y, Kim I, Jeong J, Lee J, Do M, et al. The korean mistletoe (Viscum album coloratum) extract has an antiobesity effect and protects against hepatic steatosis in mice with high-fat-diet-induced obesity. Evid Based Complement Alterna Med 2013:1-9. Doi.org/10.1155/2013/168207. [Article in Press]
Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol: Mech Dis 2010;5:145-71.
Brunt EM. Pathology of nonalcoholic steatohepatitis. Hepatol Res 2005;33:68-71.
Yang SQ, Lin HZ, Lane MD, Clemens M, Diehl AM. Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci 1997;94:2557-62.
Larter CZ, Yeh MM. Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol 2008;23:1635-48.
Chivapat S, Chavalittumrong P, Wongsinkongman P, Phisalpong C, Rungsipipat A. Chronic toxicity study of Garcinia mangostana Linn. pericarp extract. Thai J Vet Med 2011;41:45-53.
Hoseen MI, Hassan MM, Abd-Alaleem DI, Faragallah EM. Serum resistin levels and haemostatic changes in experimentally induced diabetic and high fat fed rats. J Am Sci 2010;6:217-27.
Steppan CM, Shannon TB, Savitha B, Brown EJ, Banerjee RR, Wright CM. The hormone resistin links obesity to diabetes. Nat 2001;409:307-12.
Wang J, Obici S, Morgan K, Barzilai N, Feng Z, Rossetti L. Overfeeding rapidly induces leptin and insulin resistance. Diabetes 2001;50:2786-91.
Matsuzawa Y. Adiponectin: identification, physiology and clinical relevance in metabolic and vascular disease. Atheroscler Suppl 2005;6:7-14.
Mahmoud R, Elnour WA. Comparative evaluation of the efficacy of ginger and orlistat on obesity management, pancreatic lipase and liver peroxisomal catalase enzyme in male albino rats. Eur Rev Med Pharmacol Sci 2013;17:75-83.
Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941-6.
Choi YH, Bae JK, Chae H, Kim Y, Sreymom Y, Han L, et al. Î±-Mangostin regulates hepatic steatosis and obesity through SirT1-AMPK and PPARÎ³ pathway in high fat diet-induced obese mice. J Agric Food Chem 2015;63:8399-406.