Network pharmacology, molecular docking, molecular dynamics simulation, and in vivo experiments elucidate the potential mechanisms of berberine against liver injury.

Abstract

Berberine (BBR), a compound extracted from Coptis chinensis Franch, has been used in traditional Chinese medicine to treat liver diseases due to its anti-inflammatory, antioxidant, and liver-protective properties. To explore its therapeutic effects and underlying mechanisms in CCl-induced liver injury, BBR-related targets were identified using GeneCards, TCMSP, PharmMapper, SwissTargetPrediction, and STITCH, while liver injury-related targets were collected from DisGeNET, GeneCards, TTD, and OMIM. GO and KEGG enrichment analyses were performed via DAVID, and molecular docking along with molecular dynamics simulations revealed strong, stable binding of BBR to TP53, STAT3, EGFR, IL6, CASP3, TNF, and IL-1β. These core targets were mainly enriched in TNF and p53 signaling pathways. A CCl-induced mouse liver injury model was used for in vivo validation, showing that BBR significantly reduced liver injury markers, improved histopathological changes, and downregulated expression of target genes. Together, these findings suggest that BBR alleviates liver injury by modulating inflammation and apoptosis through the TNF and p53 pathways, providing new insights into its hepatoprotective mechanisms.