Puerarin inhibits SiO2-induced pulmonary epithelial-mesenchymal transition via suppressing NF-κB activation: Insights from network pharmacology and experiment validation

Silicosis is a progressive and irreversible occupational pulmonary fibrotic disease for which no clinically available agents can effectively reverse established fibrosis. Puerarin (PUE), a natural isoflavonoid, has previously been demonstrated to exert protective effects against silicosis; however, its underlying protective mechanisms remain poorly understood. In the present study, we integrated network pharmacology, molecular docking, molecular dynamics simulations, and in vitro experiments to elucidate the therapeutic targets and mechanisms of PUE against SiO₂-induced pulmonary fibrosis. Network pharmacological analysis identified 227 potential targets of PUE for silicosis treatment. The IL-17 signaling pathway emerged as the most significantly enriched pathway, with core targets including IL6, TNF, Akt1, IL1B, ALB, EGFR, CASP3, MMP9, NF-κB1, and MAPK3. Molecular docking revealed that PUE exhibited the lowest binding energy with NF-κB1, and molecular dynamics simulations further confirmed a stable binding affinity between PUE and NF-κB1. In the SiO₂-induced BEAS-2B cell model, PUE treatment markedly inhibited NF-κB p65 phosphorylation, downregulated the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, and reversed epithelial-mesenchymal transition (EMT). Collectively, this study provides experimental evidence that the anti-fibrotic effect of PUE may be mediated by binding to NF-κB1, thereby inhibiting NF-κB signaling activation, attenuating SiO₂-induced EMT, and suppressing inflammatory responses. These findings lay a theoretical foundation for the further development of PUE as a potential therapeutic agent for silicosis.