Scoparone alleviates nonalcoholic fatty liver disease by modulating the PPARα signaling pathway

Scoparone (Scop), a natural compound derived from Artemisia capillaris Thunb, has demonstrated efficacy in improving nonalcoholic fatty liver disease (NAFLD). This study aims to explore the underlying mechanism. NAFLD was induced by a high-fat diet in C57BL/6J mice, followed by an 8-week treatment with Scop. The effect of Scop on mice NAFLD was assessed. mRNA sequencing of liver tissues was performed to identify potential targets, which were validated through in vitro experiments using palmitic acid-induced AML12 hepatocytes. The results demonstrated that Scop promoted lipid metabolism, insulin sensitivity, and liver function, and alleviated inflammation in NAFLD mice. mRNA sequencing identified the peroxisome proliferator-activated receptor α (PPARα) signaling pathway as a target of Scop, which was further confirmed by in vivo and in vitro experiments. Molecular docking studies showed that Scop could bind stably to human PPARα. In summary, Scop was proven to alleviate lipid metabolism dysfunction and inflammation by targeting the PPARα signaling pathway, which provides a basis for its potential application in NAFLD treatment.