γ-Mangostin ameliorates free fatty acid-induced lipid accumulation via the SIRT1/LKB1/AMPK pathway in HepG2 and L02 cells.

Lipid accumulation is a typical characteristic of nonalcoholic fatty liver disease (NAFLD). The inhibition of lipid accumulation is regarded as a potential treatment for NAFLD. In this study, we investigated the effects of gamma-mangostin or alpha-mangostin on lipid accumulation in a cell model. Analysis of the inhibitory effects of gamma-mangostin on lipid accumulation revealed that it downregulated NAFLD-related biochemical parameters and stimulated the SIRT1/LKB1/AMPK pathway. Consequently, it suppressed lipid synthesis and enhanced fatty acid oxidation. Moreover, we demonstrated that the blockage of AMP-activated protein kinase (AMPK) by the pharmacological inhibitor Compound C abrogated the promoting effect of AMPK. Similar results were also observed for alpha-mangostin. The effects of alpha-mangostin on lipid accumulation were inferior to those of gamma-mangostin. The differences in CPT1A activity might be originated from their different chemical structures. Our results suggested that gamma-mangostin and alpha-mangostin can be exploited as potential candidates for NAFLD treatment.