Integrating Network Pharmacology and Molecular Docking to Decipher the Anti-fibrotic Role of Fuzheng Xiezhuo Decoction Via NLRP3/TNF-α/IL-6 Pathway in Renal Fibrosis.

INTRODUCTION:The aim is to study the effect of Fuzheng Xiezhuo Decoction (FZXZD) on renal fibrosis (a marker of chronic kidney disease). METHODS:Network pharmacology and molecular docking are used to explore the active components and targets of FZXZD, and then to explore the key pathways or mechanisms of its anti-renal fibrosis. Verification is carried out with an adenine-induced renal fibrosis rat model. RESULTS:Network pharmacology and molecular docking studies have found that the NLRP3/TNF-α/IL-6 axis is the key target of FZXZD in anti-renal fibrosis. Animal experiments show that in adenine-induced nephropathy rats, FZXZD treatment improves renal function parameters and alleviates renal injury. H&E and Masson staining were performed for histopathological examination, and it was found that FZXZD could effectively reduce renal tissue damage and slow down the progression of fibrosis. Immunohistochemical analysis further confirmed that it could inhibit the expression of fibrosis markers αSMA and collagen I. Western blot results showed that FZXZD down-regulated the protein levels of fibrosis mediators (TGF-β and Smad2/3) and inflammatory cytokines (NLRP3, TNF-α, and IL-6). DISCUSSION:FZXZD exerts anti-fibrosis through a dual mechanism, inhibiting the NLRP3/TNF-α/IL-6 inflammatory axis and inhibiting the TGF-β/Smad fibrosis pathway. These findings establish NLRP3/TNF-α/IL-6 as new targets for the treatment of renal fibrosis. CONCLUSION:FZXZD inhibits the TGF-β pathway and regulates the NLRP3 pathway to reduce the release of inflammatory cytokines, thereby alleviating renal fibrosis (RF) and then relieving inflammation and renal fibrosis. This study shows that the NLRP3/TNF-α/IL-6 signaling axis is a promising mechanism of action for FZXZD in the treatment of renal fibro.