Network pharmacology-guided investigation of Fuzheng Yanggan Huaxian decoction in a CCL4-induced hepatic fibrosis mouse model: involvement of the TLR4-MAPK/NF-κB signaling axis and intestinal barrier.

OBJECTIVE

This study employed a carbon tetrachloride (CCl4)-induced hepatic fibrosis mouse model to investigate the therapeutic effects and mechanisms of Fuzheng Yanggan Huaxian Decoction (FZYGHX).

METHODS

Network pharmacology analysis was conducted to identify the Toll-like receptor 4 (TLR4)-mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway as a key regulatory axis, which was subsequently validated through in vivo experiments.

RESULTS

FZYGHX treatment preserved liver morphology, reduced serum aspartate aminotransferase and alanine aminotransferase levels, and mitigated histopathological damage. Histological assessments demonstrated improved liver architecture, reduced fibrosis, and suppressed collagen deposition. Mechanistically, FZYGHX attenuated hepatic inflammation by downregulating macrophage marker F4/80 and pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha. Furthermore, FZYGHX reinforced intestinal barrier function by upregulating tight junction (TJ) proteins (zonula occludens-1 (ZO-1), claudin-1, and occludin), while decreasing serum lipopolysaccharide (LPS) and hepatic LPS-binding protein (LBP) levels. The FITC-dextran assay confirmed restoration of mucosal barrier integrity.

CONCLUSION

These findings suggest that the anti-fibrotic effects of FZYGHX are mediated, at least in part, by inhibition of the TLR4-MAPK/NF-κB pathway and enhancement of intestinal barrier function.