Abstract This study employed a combined network toxicology and pharmacology research strategy to investigate the molecular mechanisms of perfluorooctane sulfonate (PFOS)-induced hepatic fibrosis (HF) and evaluate the intervention effects of Andrographis paniculata (AP). Potential targets of PFOS and HF were retrieved from the CTD and GEO databases, while active components and targets of AP were screened using the TCMSP platform. Protein–protein interaction (PPI) network, enrichment analysis, and molecular docking were then applied to identify key targets and pathways. The results identified 249 shared targets between PFOS and HF, significantly enriched in inflammatory response, oxidative stress, and the TNF/NF-κB signaling pathway. Core targets such as IL1B, CXCL8, EGFR, and PTGS2 were identified by PPI analysis, and molecular docking confirmed strong binding affinity between PFOS and these proteins. Additionally, 49 common targets were found between AP and HF, mainly involved in PPAR and MAPK signaling pathways and arachidonic acid metabolism, with high binding activity to AP's active components. In summary, PFOS may be involved in hepatic fibrosis by regulating inflammation- and oxidative stress-related pathways via targets such as EGFR and PTGS2, whereas AP may counteract this effect through multi-target mechanisms that suppress inflammation, alleviate oxidative stress, and inhibit abnormal extracellular matrix deposition. These findings offer a theoretical foundation for understanding PFOS hepatotoxicity and supporting the clinical application of AP.
Wang et al. (Fri,) studied this question.