Unveiling the mechanism of madecassic acid in nonalcoholic fatty liver disease: a network pharmacology and experimental validation

Madecassic acid (MA), a triterpenoid derived from Centella asiatica, exhibits diverse pharmacological properties. Despite its potential, the mechanisms underlying its effects on insulin resistance and lipid metabolism remain unclear. This study aimed to elucidate the pharmacological properties of MA in nonalcoholic fatty liver disease (NAFLD) via network pharmacology and experimental validation. A network pharmacology analysis was conducted to identify potential therapeutic targets of MA in NAFLD. Target genes were retrieved from GeneCards and other relevant databases, and a component–target–disease network was constructed. Furthermore, the effect of MA on the in vitro model of NAFLD, insulin resistance, and oxidative stress were determined in HepG2 and Raw 264.7 cells. Network pharmacology analysis revealed that MA involves anti-inflammation and lipid metabolic pathways. Experimental validation confirmed the ability of MA to suppress proinflammatory gene expression (IL-6, Tnf-α, Mcp-1), reduce oxidative stress, and modulate lipid metabolism dysregulation by ameliorating Srebp-1c and Fasn overexpression, preventing Cpt-1 downregulation, and enhancing glucose utilization. Our findings suggest that MA is a potential therapeutic option for NAFLD and its associated complications.