Dahuang Fuzi decoction attenuates renal fibrosis via suppression of the NF-κB pathway.

BACKGROUND

Renal fibrosis is a key pathological process in chronic kidney disease with limited treatment options. Dahuang Fuzi Decoction (DFT), a classic traditional Chinese medicine formula, shows therapeutic potential, but its anti-fibrotic mechanism remains unclear.

METHODS

The anti-fibrotic effect of DFT was assessed in a unilateral ureteral obstruction (UUO) rat model via histopathological examination and renal function tests. The underlying mechanism was investigated using an integrated strategy which included serum pharmacology with drug-containing serum from treated rats, network pharmacology to screen bioactive compounds and predict targets, and in vitro validation in angiotensin II (Ang II)-stimulated NRK-52E cells, with a focused analysis of the nuclear factor κB (NF-κB) signaling pathway.

RESULTS

DFT treatment ameliorated renal injury, reduced collagen deposition, and improved biochemical parameters in UUO rats. DFT-containing serum attenuated Ang II-induced fibrotic responses in cells. Bioinformatics and experimental validation identified the NF-κB pathway as a key target. DFT suppressed p65 nuclear translocation and downstream target gene expression in both UUO kidney tissue and Ang II-stimulated NRK-52E cells, and pharmacological activation of this pathway reversed the protective effects of DFT.

CONCLUSION

DFT alleviates renal fibrosis, at least in part by inhibiting the NF-κB signaling pathway, as validated in both UUO kidney tissue and Ang II-stimulated tubular epithelial cells, providing a pharmacological basis for its clinical application.