Abstract
Renal fibrosis represents a common pathological pathway in various chronic kidney diseases (CKD). Jiawei Fangji Huangqi decoction (JFH) is a traditional Chinese herbal formula and has been clinically prescribed in China. The aim of this study was to determine the role of JFH in renal fibrosis using a unilateral ureteral obstruction (UUO) mouse model and explore its underlying mechanisms. In UUO mice, JFH was found to inhibit the accumulation of extracellular matrix (ECM) proteins, as demonstrated by Masson staining, and reduce the expression of fibrotic markers and TGF-β1 in obstructed kidneys, as confirmed by Western blotting analysis. JFH was closely correlated with the amelioration of epithelial-mesenchymal transition (EMT) as shown by Western blotting analysis. Mechanistic investigations via network pharmacology analysis indicated that inflammatory pathways represent downstream targets of JFH in renal fibrosis. Quantitative PCR analysis revealed that the pro-inflammatory cytokines TNF-α and IFN-γ were upregulated by UUO surgery, whereas JFH treatment significantly attenuated their expression in fibrotic kidneys. The anti-inflammatory effect of JFH was shown by inactivation of the NF-κB signaling pathway and reduced expression of the macrophage marker F4/80 and the M1 polarization marker CD86 in UUO-induced renal tissues. Furthermore, JFH was found to inactivate the NLRP3 inflammasome, as reflected by decreased expression of NLRP3 and IL-1β, which correlated with reduced expression of the transcriptional factor STAT1 in obstructed kidneys. In conclusion, JFH alleviates renal fibrosis by inhibiting TGF-β1, EMT and inflammation, highlighting the therapeutic potential of JFH for treating CKD patients, particularly those with prominent inflammatory responses.