Alpha Mangostin and Xanthone from Mangosteen (Garcinia mangostana L.) Role on Insulin Tolerance and PPAR-γ in Preclinical Model Diabetes Mellitus


insulin tolerance

How to Cite

Welly Ratwita, Elin Yulinah Sukandar, NengFisheriKurniati , & I Ketut Adnyana. (2018). Alpha Mangostin and Xanthone from Mangosteen (Garcinia mangostana L.) Role on Insulin Tolerance and PPAR-γ in Preclinical Model Diabetes Mellitus. Journal of Pharmacy and Nutrition Sciences, 8(3), 83–90.


Objective: This research elaborated role of alpha mangostin and xanthone on insulin resistance and peroxisome proliferator–activated receptor (PPAR)-γ by measuring blood glucose level and PPAR- γ expression on adipocyte cell culture.

Methods: Insulin tolerance test were conducted using male wistar rat divided into 9 groups, which were normal, control (D-Glucose induced only), glibenclamide, various doses of a-mangostin and xanthone (5, 10, 20 mg/kgbw). All group induced by D-glucose 3 g/kg orally 30 minutes later. Blood glucose levels changes were observed at 90th and 150th minute. While other study observed PPAR-γ expression on adipocyte cell culture that treated with a-mangostin/xanthone/pioglitazone in various concentration.

Results: KITT in all treatment groups were significantly different (p<0.05) when compared to the positive control group, except xanthone 5 mg/kgbw. This suggests that a-mangostin 5, 10 and 20 mg/kgbw, xanthone 10 and 20 mg/kgbw, as well as metformin, have the effect of lowering insulin resistance in white rats given a 10-day fatty emulsion. Almost similar with thiazolinedione, alpha mangostin and xanthone increase PPAR-g expression in adipocyte when the concentration bigger. But xanthone effect not as good as α-mangostin or thiazolinedione effect.

Conclusion: Alpha mangostin and xanthone are two substances that showed potential effect to improve insulin tolerance by increasing PPAR-g in adipocyte.


Gorelick J, Kitron A, et al. Anti-diabetic activity of Chiliadenus iphionoides. Journal of Ethnopharmacology 2011; 137(3): 1245-1249.

Yu Z, Yin Y, Zhao W, Liu J, Chen F. Anti-diabetic activity peptides from albumin against ?-glucosidase and ?-amylase. Journal of Food Chemistry 2012; 135: 2078-2085.

Yu Z, Yin Y, et al. Characterization of ACE-inhibitory peptide associated with antioxidant and anticoagulation properties. Journal of Food Science 2011; 76 (8): 1149-1155.

Yu Z, Yin Y, et al. Novel peptides derived from egg white protein inhibiting alpha-glucosidase. Food Chemistry 2011; 129(4): 1376-1382.

Orme CM, Bogan JS. Sorting out diabetes. Science 2009; 324: 1155-1156.

Yu Z, Yin Y, Zhao W, Liu J, Chen F. Anti-diabetic activity peptides from albumin against ?-glucosidase and ?-amylase. Food Chemistry 2012; 135: 2078-2085.

Shepherd PR, Kahn BB, Glucose transporters and insulin action, implication for insulin resistance and diabetes mellitus. The New England Journal of Medicine 1999; 341(4): 248-256.

Klaus S. Adipose tissue as a regulator of energy balance. Curr Drug Targets 2004; 5: 241-250.

Faraj M, Lu HL, Cianflone K. Diabetes, lipids, and adipocyte secretagogues. Biochem Cell Biol 2004; 82: 170-190.

Das M, Gabriely I, Barzilai N. Caloric restriction, body fat and ageing in experimental models. Obes Rev 2004; 5: 13-19.

Fluck CE, Slotboom J, Nuoffer JM, Kreis R, Boesch C, Mullis PE. Normal hepatic glycogen storage after fasting and feeding in children and adolescents with type 1 diabetes. Pediatr Diabetes 2003; 4: 70-76.

El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 2004; 126: 460-468.

Cohen SE, Tseng YH, Michael MD, Kahn CR. Effects of insulin-sensitizing agents in mice with hepatic insulin resistance. Diabetologia 2004; 47: 407-411.

Wright EM, Turk E, Zabel B, Mundlos S, Dyer J. Molecular genetics of intestinal glucose transport. J Clin Invest 1991; 88: 1435-40.

DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev 1997; 5: 177-269.

Taher M, Amiroudine MZAM, Zakaria TMFST, Susanti D, Ichwan SJA, Kaderi MA, Ahmed OU, Zakaria ZA. ?-Mangostin improves glucose uptake and inhibits adipocytes differentiation in 3T3-L1 Cells via PPAR-?, GLUT-4, and leptin expressions. Evidence-Based Complementary and Alternative Medicine 2015; 2015: 1-9.

Aisha A, Abu-Salah K, Siddiqui M, Ismail Z, Majid A. Quantification of ?-, ?- dan ?-mangostin in Garcinia mangostana fruit rind extracts by a reverse phase high performance liquid chromatography. Journal of Medicinal Plants Research 2012; 6(29): 4526-4534.

Chaverri J, Rodr?guez N, Ibarra M, Rojas J. Medical properties of mangosteen (Garcinia mangostana). Food and Chemical Toxicology 2008; 46: 3227-3239.

Reddy J, Ravikumar N, Gaddamanugu G, Naresh K, Rajan S, Solomon K. Synthesis, crystal structure, spectral charac-terization and fluorescence studies of salts of ?-mangostin with APIs. Journal of Molecular Structure 2013: 137-143.

Ryu H, Cho J, Long M, Yuk H, Kim Y, Jung S, Lee B, Park K. ?-glukosidase inhibition and antihyperglycemic activity of prenylated xanthones from Garcinia mangostana. Journal of Phytochemistry 2011; 72: 2148-2154.

Ai J, Wang N, Yang M, Du ZM, Zhang YC, Yang BF. Development of Wistar rat model of insulin resistance, World Journal of Gastroenterology 2005; 11(24): 3675-3679.

Winzell MS, Ahre´n B. The high-fat diet-fed mouse a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 2004; 53(3): 215-19.

Gregoire FM, Smas CM, Sul HS. Understanding adipocyte differentiation. American Physiological Society Journal 1998; 78(3): 783-809.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods 1993; 65(2): 55-63.

Susantia D, Amiroudineb MZAM, Rezalic MF, Taherb M. Friedelin and lanosterol from Garcinia prainiana stimulated glucose uptake and adipocytes differentiation in 3T3-L1 adipocytes. Natural Product Research 2013; 27(4-5): 417-424.

Shin E, Choi KM, Yoo HS, Lee CK, Hwang BY, Lee MK. Inhibitory effects of coumarins from the stem barks of Fraxinus rhynchophylla on adipocyte differentiation in 3T3-L1 cells. Biological and Pharmaceutical Bulletin 2010; 33(9): 1610-1614.

Matsuura N, Gamo K, Miyachi H, Iinuma M, Kawada T, Takahashi N, Akao Y, Tosa H. ?-Mangostin from Garcinia mangostana Pericarps as a dual agonist that activates both PPAR-? and PPAR-?. Biosci Biotechnol Biochem 2013; 77(12): 2430-2435.

Dubois M, Pattou F, Kerr-Conte J, Gmyr V, Vandewalle B, Deremaux P, Auwerx J, Schoonjans K, Lefebvre J. Expression of peroxisome proliferator-activated receptor ? (PPAR-?) in normal human pancreatic islet cells. Diabetologia 2000; 43: 1165-1169.

Hoftnann CA, Colca JR. New oral thiazolidinedione antidiabetic agents act as insulin sensitizers. Diabetes Care 1992; 15: 1075-1078.

Willson TM, Cobb JE, Cowan DJ, Wiethe RW, Correa ID, Prakash SR, Beck KD, Moore LB, Kliewer SA, Lehmann JM. The structure-activity relationship between peroxisome proliferator-activated receptor ? agonist and the antihyperglycemic activity of thiazolidinediones. J Med Chem 1996; 39: 665-668.

Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM. mPPAR72, tissue specific regulator of an adipocyte enhancer. Genes Dev 1994; 8: 1224-1234.

Hotamisligil GS, Spiegelman BM. Tumor necrosis factor ?: a key component. Diabetes 1997; 46.

Hofmann C, Lorenz K, Braithwaite SS, Colca JR, Palazuk BJ, Hotamisligil GS, Spiegelman BM. Altered gene expression for tumor necrosis factor-? and its receptors during drug and dietary modulation of insulin resistance. Endocrinology 1994; 134: 264-270.

Zncke YF, Hallakou RS, Doare L, Foufelle F, Kergoat M, Guerre-Millo M, Berthault MF, Dugail I, Morin J, Auwerx J, Ferre P. Pioglitazone induces in vivo adipocyte differentiation in the obese. Diabetes 1997; 1393-1399.

Lehmann JM, Moore LB, Smith-Oliver TA, Wilkinson WO, Wilson TM, Kliewer SA. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor ? (PPAR-?). J Biol Chem 1995; 270: 12953-12956.

Kletzien RF, Clarke SD, Ulrich RG. Enhancement of adipocyte differentiation by an insulin-sensitizing agent. Mol Pharmacol 1992; 41: 393-398.

Sandouk T, Reda D, Hofmann C. Antidiabetic agent pioglitazone enhances adipocyte differentiation of 3T3-F442A cells. Am J Physiol 1993; 264: 1600-1608.

Brun RP, Tontonoz P, Forman BM, Ellis R, Chen J, Evans RM, Spiegelman BM. Differential activation of adipogenesis by multiple PPAR isoforms. Genes Dev 1996; 10: 974-984.

Ratwita W, Sukandar EY, Adnyana IK, Kurniati NF, Alpha mangostin and xanthone from mangosteen (Garcinia mangostana l.) role on glucose tolerance and glucose transporter-4 in diabetes mellitus. International Journal of Pharmacognosy and Phytochemical Research 2017; 9(9): 1206-1212.

Taher M, Amiroudine MZAM, Syafiq TMF, Zakaria T, Susanti D, Ichwan SJA, Kaderi MA, Ahmed QU, Zakaria ZA. ?-Mangostin improves glucose uptake and inhibits adipocytes differentiation in 3T3-L1 cells via PPAR-?, GLUT-4, and leptin expressions. Evidence-Based Complementary and Alternative Medicine 2015; 1-9.

Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell 2001; 104(4): 531-543.

Yun JW. Possible anti-obesity therapeutics from nature-a review. Phytochemistry 2010; 71(14-15): 1625-1641.

V´azquez-Vela MEF, Torres N, Tovar AR. White adipose tissue as endocrine organ and its role in obesity. Archives of Medical Research 2008; 39(8): 715-728.

Brun RP, Spiegelman BM. PPAR-gamma and the molecular control of adipogenesis. Journal of Endocrinology 1997; 155(2): 217-218.

Choi SS, Cha BY, Iida K. Artepillin C. as a PPAR-? ligand, enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. Biochemical Pharmacology 2011; 81(7): 925-933.

Huang C, Zhang Y, Gong Z. Berberine inhibits 3T3-L1 adipocyte differentiation through the PPAR? pathway. Biochemical and Biophysical Research Communications 2006; 348(2): 571-578.

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Copyright (c) 2018 Welly Ratwita , Elin Yulinah Sukandar , Neng Fisheri Kurniati  , I Ketut Adnyana