Abstract
Asiatic acid (AA) is a pentacyclic triterpene derived from the traditional medicine Centella asiatica. It is known for its anti-inflammatory, antioxidant, and lipid-regulating properties. Though previous studies have suggested its potential therapeutic benefits for atherosclerosis, its pharmacological mechanism is unclear. The objective of this study was to investigate the molecular mechanism of AA in the treatment of atherosclerosis. Therefore, network pharmacology was employed to uncover the mechanism by which AA acts as an anti-atherosclerotic agent. Furthermore, molecular docking, molecular dynamics (MD) simulation, and in vitro experiments were performed to elucidate the mechanism of AA's anti-atherosclerotic effects. Molecular docking analysis demonstrated a strong affinity between AA and PPARγ. Further MD simulations demonstrated the favorable stability of AA-PPARγ protein complexes. In vitro experiments demonstrated that AA can dose-dependently inhibit the expression of inflammatory factors induced by lipopolysaccharide (LPS) in RAW264.7 cells. This effect may be mediated through the PPARγ/NF-κB signaling pathway. This research underscores anti-inflammation as a crucial biological process in AA treatments for atherosclerosis, with PPARγ potentially serving as a key target.