Alpha-Mangosteen lessens high-fat/high-glucose diet and low-dose streptozotocin induced-hepatic manifestations in the insulin resistance rat model

• Main Authors: Vivian Soetikno (Author), Prisma Andini (Author), Miskiyah Iskandar (Author), Clark Christensen Matheos (Author), Joshua Alward Herdiman (Author), Iqbal Kevin Kyle (Author), Muhammad Nur Imaduddin Suma (Author), Melva Louisa (Author), Ari Estuningtyas (Author)
• Format: Book
• Published: Taylor & Francis Group, 2023-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1080/13880209.2023.2166086; 1744-5116; 1388-0209
• Keywords: Fatty liver; hyperglycemia; dietary fats; inflammation; metabolic syndrome; diabetes; Therapeutics. Pharmacology; RM1-950
• Source: Pharmaceutical Biology, Vol 61, Iss 1, Pp 241-248 (2023)

AbstractContext α-Mangosteen (α-MG) attenuates insulin resistance (IR). However, it is still unknown whether α-MG could alleviate hepatic manifestations in IR rats.Objective To investigate the effect of α-MG on alleviating hepatic manifestations in IR rats through AMP-activated protein kinase (AMPK) and sterol-regulatory element-binding protein-1 (SREBP-1) pathway.Materials and methods IR was induced by exposing male Sprague-Dawley rats (180-200 g) to high-fat/high-glucose diet and low-dose injection of streptozotocin (HF/HG/STZ), then treated with α-MG at a dose of 100 or 200 mg/kg/day for 8 weeks. At the end of the study (11 weeks), serum and liver were harvested for biochemical analysis, and the activity of AMPK, SREBP-1c, acetyl-CoA carboxylase (ACC), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, insulin receptor substrate (IRS)-1, Bax and liver histopathology were analyzed.Results α-MG at both doses significantly lowered ALT, AST, triglyceride, and cholesterol total by 16.5, 15.7, 38, and 36%, respectively. These beneficial effects of α-MG are associated with the downregulation of the IR-induced inflammation in the liver. Furthermore, α-MG, at both doses, activated AMPK by 24-29 times and reduced SREBP-1c by 44-50% as well as ACC expression by 19-31% similar to metformin. All treatment groups showed liver histopathology improvement regarding fat deposition in the liver.Conclusions Based on the findings demonstrated, α-MG protected against HF/HG/STZ-induced hepatic manifestations of the IR rats, at least in part via the modulation of the AMPK/SREBP-1c/ACC pathway and it could be a potential drug candidate to prevent IR-induced hepatic manifestations.