Integrated serum pharmacochemistry, network pharmacology and experimental verification to explore the mechanism of Angelicae Pubescentis Radix in the treatment of NASH.

This study aimed to evaluate the therapeutic potential of Angelicae Pubescentis Radix (APR) against non-alcoholic steatohepatitis (NASH) and elucidate its underlying mechanisms through an integrated approach combining network pharmacology, molecular docking and experimental validation. Serum pharmacochemistry and network pharmacology were employed to identify bioactive compounds in APR and their potential targets related to NASH. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced NASH mouse model was established to evaluate the therapeutic effects of APR. Serum analysis identified eight bioactive compounds derived from APR. The possible targets and key pathways of the components absorbed into serum of APR were predicted by network pharmacology. Molecular docking studies confirmed strong binding affinities between the core bioactive compounds and their respective targets. In vivo experiments demonstrated that APR significantly alleviated liver injury and improved serum lipid profiles in NASH mice. Furthermore, APR partially restored the mRNA levels of candidate targets and downregulated the expression of the macrophage activation marker F4/80. Additionally, APR modulated key protein expression levels in the liver, including Caspase-3, Cleaved Caspase-3, and Bcl-2, consistent with the proposed mechanism of action. These findings systematically revealed that the multi-target therapeutic effects of APR against NASH are mediated through the regulation of the apoptosis pathway, providing novel insights into the hepatoprotective mechanisms of APR. In conclusion, this study highlights the potential of APR as a promising therapeutic agent for NASH and elucidates its multi-target pharmacological mechanism, offering a foundation for further research and clinical applications.