Arctiin attenuated NASH by inhibiting glycolysis and inflammation via FGFR2/CSF1R signaling.

The present work was conducted to evaluate the pharmacological effect of Arctiin(ARC) on high fat diet(HFD)-induced Non-alcoholic steatohepatitis(NASH) and investigate its potential mechanism. The network pharmacology and bioinformatic analyses predicted that FGFR2 might be the potential target of ARC. Palmitic acid(PA)-induced AML12 cell was employed as the in vitro model. ARC reduced the levels of ALT, AST, TC, TG, and attenuated histopathological alteration. ARC inhibited inflammatory cytokines, inflammatory molecules, downregulated the expressions of FGFR2/CSF1R, inhibited glycolysis and promoted oxidative phosphorylation both in vivo and in vitro. ARC enhanced mitochondrial membrane potential and reduced oxidative stress. The application of FGFR2-OE plasmid, CSF1R-OE plasmid, CSF1R inhibitor PLX indicated that ARC attenuated glycolysis and inflammation in PA-induced AML12 cells via FGFR2/CSF1R signaling. HIF1A was proved to be involved in this process using HIF1A agonist DEF and HIF1A inhibitor PX478. Molecular docking and molecular dynamic suggested that ARC might combine with FGFR2. In conclusion, the present study demonstrated that ARC ameliorated NASH by inhibiting glycolysis and inflammation via FGFR2/CSF1R signaling.