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

Abstract

Context

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.

Keywords:

• Fatty liver
• hyperglycemia
• dietary fats
• inflammation
• metabolic syndrome
• diabetes
• streptozotocin

Acknowledgements

The authors thank to Nur Rahadiani, PhD, MD, and Chyswyta Chaliana for technical assistance.

Author contributions

Study design: Vivian Soetikno; Data collection: Prisma Andini, Miskiyah Iskandar, Clark Christensen Matheos, Joshua Alward Herdiman, Iqbal Kevin Kyle, Muhammad Nur Imaduddin Suma; Statistical analysis: Melva Louisa, Vivian Soetikno; Data Interpretation: Vivian Soetikno, Prisma Andini, Miskiyah Iskandar, Clark Christensen Matheos, Joshua Alward Herdiman, Iqbal Kevin Kyle, Muhammad Nur Imaduddin Suma, Melva Louisa, Ari Estuningtyas; Manuscript preparation: Vivian Soetikno; Literature search: Vivian Soetikno, Prisma Andini, Miskiyah Iskandar, Clark Christensen Matheos, Joshua Alward Herdiman, Iqbal Kevin Kyle, Muhammad Nur Imaduddin Suma, Melva Louisa, Ari Estuningtyas; Funds collection: Vivian Soetikno

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research project was financially supported by the Universitas Indonesia [Grant number: NKB-1289/UN2.RST/HKP.05.00/2020].