Anti-hepatic Fibrosis Potential of Ailanthone, A Quassinoid Isolated from Ailanthus altissima

Ailanthone is an active ingredient isolated from Ailanthus altissima (Mill.) Swingle, Simaroubaceae, which is a traditional medicine widely used in the treatment of liver ailments. Ailanthone has been found to suppress the occurrence and progression of hepatic fibrosis, yet the molecular mechanism of its anti-hepatic fibrosis activity remains unclear. Thus, we aimed to perform in vitro experiments and network pharmacology to investigate the anti-hepatic fibrosis effect and potential mechanism of ailanthone. In this study, we explored the drug-likeness, bioavailability, and hepatotoxic parameters of ailanthone using the SwissADME, ADMETlab, and ProTox-II servers. We also assessed the anti-hepatic fibrosis activity of ailanthone using hepatic stellate cells. Finally, we demonstrated the potential targets and pharmacological mechanisms of ailanthone against hepatic fibrosis through network pharmacology and molecular docking. Ailanthone exhibited favorable drug-likeness and bioavailability as well as inactive hepatotoxic properties. In addition, it exerted significant inhibitory and pro-apoptotic effects on hepatic stellate-T6 cells in a dose-dependent manner. Network pharmacology and molecular docking indicated that these effects can be achieved by modulating the expression of targets (including epidermal growth factor receptor, insulin-like growth factor I, fibroblast growth factor 2, hepatocyte growth factor receptor, and mammalian target of rapamycin) on the phosphatidylinositol 3-kinase-protein kinase B pathway. This work provided theoretical support for advancing ailanthone as a possible anti-fibrotic agent.