Decoding Schisandra chinensis Bioactives and Multitarget Action against Drug-Induced Liver Injury via Integrated Spectrum–Effect, Network Pharmacology, and Molecular Modeling

Abstract Drug-induced liver injury (DILI) continues to rise globally, underscoring an urgent need for effective and safe therapeutic strategies. Schisandra chinensis, a dual-purpose food and medicinal herb in traditional Chinese practice, exhibits notable hepatoprotective activity and favorable safety characteristics. However, its bioactive constituents and underlying anti-DILI mechanisms remain insufficiently defined, limiting its translational potential. This study integrates spectrum–effect correlation analysis, network pharmacology, molecular docking, and molecular dynamics to systematically elucidate the material basis and polypharmacological mechanisms underlying the anti-DILI activity of S. chinensis. Spectrum–effect relationship analysis identified schisandrin B, schisandrol B, and schisandrin A as key bioactive markers associated with therapeutic efficacy. Network pharmacology further elucidated the interactions between common peak components and DILI-related targets, identifying AKT1, STAT3, JUN, and TNF as key nodes in the protein–protein interaction network and schisandrol B, schisantherin B, schisandrol A, and schisandrin B as core bioactive constituents. Based on these findings, molecular docking and molecular dynamics simulations were performed to validate the interactions between schisandrin B or schisandrol B and the core targets. The simulations demonstrated stable binding interactions and favorable binding affinities, supporting their roles as primary functional constituents.