Abstract
PURPOSE: The objective of this study is to investigate the efficacy of the Shenlian (SL) decoction on regulating cellular pyroptosis and macrophage M1 polarization in the treatment of diabetic nephropathy (DN), and to elucidate its mechanism of action through the use of animal and cellular experiments. METHODS: The potential targets for SL decoction were predicted using the TCMSP and Swiss Target databases. The differential genes for DN were obtained using the GeneCards database, and potential mechanisms for the treatment of DN with SL decoction were explored through enrichment analysis. The efficacy of SL decoction in the treatment of DN and its regulation of macrophage polarization and pyroptosis were evaluated in vivo using db/db mice. The RAW264.7 cell line and the TCMK-1 cell line were cultured in vitro. The objective was to investigate the effect of SL decoction on the inhibition of M1 macrophage polarization and scorched death of renal tubular epithelial cells (TECs). RESULTS: The results of the enrichment analysis indicated that the Toll-like signaling pathway was a principal pathway in the treatment of DN with SL decoction. The results of animal and cellular experiments demonstrated that SL decoction has the potential to enhance renal function in patients with DN, while simultaneously reducing the concentration of serum inflammatory factors. Additionally, it was observed that SL decoction could inhibit the infiltration of macrophages and the polarization of macrophages into the M1 phenotype. Furthermore, the activation of the TLR4 signaling pathway and the pyroptosis of renal tubular cells were also inhibited by SL decoction. CONCLUSION: This study employed network pharmacology and in vivo and in vitro experiments to confirm that SL decoction can improve renal function in patients with DN. The results demonstrated that the mechanism of action of SL decoction is related to regulating the M1 polarization of macrophages in the DN kidney and inhibiting the pyroptosis of renal TECs.