Molecular mechanisms of Picroside II in fatty liver. Proposed mechanism of action of Picroside II on FFA accumulation, oxidative stress and mitochondrial dysfunction: Picroside II attenuated FFA accumulation in HepG2 cells by downregulation of FATP5, SREBP-1 and SCD, hence decreasing fatty acid uptake and lipid synthesis. Picroside II decreases the production of ROS, increases the levels of antioxidants (glutathione, Manganese superoxide dismutase and Catalase). Picroside II improves mitochondrial functions by increasing ATP production, decreasing ΔΨM loss and increasing cytochrome c expression. (The figure is adopted and modified further from; Dhami-Shah H, Vaidya R, Talwadekar M, Shaw E, Udipi S, Kolthur-Seetharam U, Vaidya ADB. Intervention by Picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells. J Ayurveda Integr Med. 2021 Jul–Sep; 12(3):465–473′). FFA, Free Fatty Acid; FATP5, Fatty Acid Transporter Protein 5; SREBP-1, Sterol Regulatory Element-Binding Protein-1; SCD, Stearoyl CoA Desaturase; ROS, Reactive Oxygen Species; ATP, Adenosine Triphosphate; ΔΨM, Mitochondrial Membrane Potential.