Alpha-Mangostin Improves Cardiac Hypertrophy and Fibrosis and Associated Biochemical Parameters in High-Fat/High-Glucose Diet and Low-Dose Streptozotocin Injection-Induced Type 2 Diabetic Rats

Vivian Soetikno; Andriyani Murwantara; Prisma Andini; Fabrian Charlie; Gilbert Lazarus; Melva Louisa; Wawaimuli Arozal

doi:10.2147/JEP.S233111

Alpha-Mangostin Improves Cardiac Hypertrophy and Fibrosis and Associated Biochemical Parameters in High-Fat/High-Glucose Diet and Low-Dose Streptozotocin Injection-Induced Type 2 Diabetic Rats

J Exp Pharmacol. 2020 Jan 28:12:27-38. doi: 10.2147/JEP.S233111. eCollection 2020.

Authors

Vivian Soetikno¹, Andriyani Murwantara², Prisma Andini², Fabrian Charlie², Gilbert Lazarus³, Melva Louisa¹, Wawaimuli Arozal¹

Affiliations

¹ Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, 10430, Indonesia.
² Graduate Course, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.
³ Undergraduate Course, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.

Abstract

Purpose: The aim of present study was to analyze the effect of alpha-mangostin on cardiac hypertrophy and fibrosis and biochemical parameters in high-fat/high-glucose diet and low-dose streptozotocin injection (HF/HG/STZ)-induced type 2 diabetic rats.

Methods: Diabetes was induced in male Wistar rats by giving a combination of high-fat/high-glucose (HF/HG) diet for 3 weeks and followed by low-dose streptozotocin intraperitoneal injection (STZ; 35 mg/kg) at Week-3 and the HF/HG diet was continued until 8 weeks. The diabetic rats were then divided into four groups (each, n=6): untreated diabetic group (HF/HG/STZ); diabetic group treated with metformin 200 mg/kg/day (HF/HG/STZ+Metformin); diabetic group treated with alpha-mangostin 100 mg/kg/day (HF/HG/STZ+AM100); and diabetic group treated with alpha-mangostin 200 mg/kg/day (HF/HG/STZ+AM200) and all were given by oral gavage for 8 weeks. We also included a control group (C) treated with AM200 (C+AM200). The role of alpha-mangostin was assessed through its effect on blood glucose levels, HOMA-IR, blood pressure, body weight, pro-inflammatory cytokines in cardiac tissue, serum aminotransferases (ALT and AST), lipid profiles (cholesterol and triglyceride), blood urea nitrogen (BUN), uric acid, cardiac hypertrophy and fibrosis.

Results: Diabetic rats treated with alpha-mangostin in both doses for 8 weeks showed decrease in blood glucose levels, HOMA-IR, and blood pressure. Alpha-mangostin treatment also prevented HF/HG/STZ-induced changes in the activities of ALT, AST, BUN, uric acid, lipid profiles, and pro-inflammatory cytokines, which were comparable with the standard drug metformin, while alpha-mangostin did not show any significant effects on control rats (p>0.05). The cardiac hypertrophy and fibrosis were also attenuated in diabetic rats treated with alpha-mangostin in both doses.

Conclusion: These data suggest that administration of alpha-mangostin can effectively attenuate diabetes-induced alteration in cardiac hypertrophy and fibrosis as well as biochemical parameters in HF/HG/STZ rats.

Keywords: cardiomyopathy; diabetes mellitus; dietary fats; hyperglycemia; hyperinsulinemia; insulin resistance.