Integrated In Silico and Network Pharmacology Assessment of Procyanidin C1 against Oxidative, Inflammatory, and Fibrogenic Targets in Hepatotoxicity

Background Hepatotoxicity arises from complex and interconnected mechanisms involving oxidative stress, inflammation, nitrosative damage, and fibrogenesis. Therapeutic strategies targeting a single pathway have shown limited success, highlighting the need for multi-target approaches. Procyanidin C1, a naturally occurring polyphenolic compound, has demonstrated antioxidant and anti-inflammatory properties, but its systems-level molecular interactions in hepatotoxicity remain insufficiently characterized. Objective This study aimed to investigate the multi-target interaction profile of procyanidin C1 against key proteins involved in hepatotoxicity using an integrated in silico and network pharmacology approach. Methods Molecular docking was performed to evaluate the binding affinity of procyanidin C1 against five hepatotoxicity-related targets: cytochrome P450 2E1 (CYP2E1), tumour necrosis factor-alpha (TNF-α), Kelch-like ECH-associated protein 1 (Keap1), inducible nitric oxide synthase (iNOS), and transforming growth factor beta-1 (TGF-β1). Binding affinities and root mean square deviation (RMSD) values were used to assess interaction strength and pose stability. Network pharmacology analysis was conducted using STRING, KEGG, Gene Ontology, Reactome, and Cytoscape to map target connectivity and pathway enrichment. Results Procyanidin C1 exhibited favorable binding across all targets, with binding energies ranging from − 7.6 to -10.6 kcal/mol and RMSD values below 2.0 Å. The strongest interaction was observed with Keap1 (-10.6 kcal/mol), followed by CYP2E1 (-9.1 kcal/mol), iNOS (-8.3 kcal/mol), TNF-α (-8.0 kcal/mol), and TGF-β1 (-7.6 kcal/mol). Network pharmacology analysis revealed that these targets converge on pathways related to antioxidant defence, inflammatory signalling, nitric oxide metabolism, xenobiotic biotransformation, apoptosis, and fibrogenesis. Conclusion The findings suggest that procyanidin C1 exhibits a multi-target interaction profile relevant to key mechanisms of hepatotoxicity, supporting its potential as a systems-level modulator of liver injury pathways and warranting further experimental validation.