Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that threatens public health, and current therapies remain limited. This study investigated the protective effect of magnesium isoglycyrrhizinate (MGL), a novel compound, against free fatty acid (FFA)-induced lipotoxicity in a cellular model of steatosis. Methods: HepG2 cells were incubated with 1 mmol/l FFAs together with MGL for 24 h. Cell viability was assessed using the MTT assay. Cell apoptosis was determined by Hoechst staining. Intracellular lipids were measured by flow cytometry using Nile red. Mitochondrial function was analyzed by detecting transmembrane potential, cytochrome c release and reactive oxygen species’ production. Results: MGL protected cell viability and dramatically decreased FFA-induced cell apoptosis and lipid accumulation. MGL was found to inhibit mitochondrial transmembrane polarization, and decrease mitochondrial cytochrome c release and the generation of reactive oxygen species. Conclusion: This study demonstrated that MGL attenuates FFA-induced lipotoxicity by reducing mitochondrial damage, which indicates a promising therapeutic intervention for NAFLD.

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