Fu-Gan-Hua-Xian Decoction Attenuates Liver Fibrosis via Circadian Clock Regulation

Abstract Objective: This study aimed to explore the antifibrotic effects of Fu-Gan-Hua-Xian decoction (FGHXT) in a CCl4-induced liver fibrosis rat model and to determine whether its therapeutic benefits are associated with the regulation of circadian clock genes Clock and Bmal1. Methods:A liver fibrosis model was established using CCl4 induction in rats, followed by FGHXT intervention. Liver histopathology was assessed by H&E and Masson staining. The expression levels of fibrosis markers (LN, Col IV, and PC III) and circadian clock genes Clock and Bmal1 were analyzed using RT-PCR and Western blot. Results: Compared with the control group, Clock (p<0.01) and Bmal1 (p<0.05) expression were significantly downregulated in the model group, indicating circadian rhythm disruption in liver fibrosis. FGHXT administration significantly upregulated Clock and Bmal1 expression, suggesting a restoration of circadian function. Additionally, fibrosis markers (LN, Col IV, and PC III) were markedly reduced in the FGHXT-treated group. Histological analysis revealed a decrease in collagen deposition and inflammatory cell infiltration, further confirming the antifibrotic effects of FGHXT. Conclusion: Our findings suggest that FGHXT alleviates liver fibrosis by modulating circadian clock genes Clock and Bmal1, potentially through the TGF-β1 signaling pathway. These results provide novel insights into the circadian-based mechanisms underlying the antifibrotic effects of FGHXT, highlighting its potential as a therapeutic strategy for liver fibrosis.