Panaxatriol saponins exert anti-renal fibrosis by suppressing TNF-α mediated inflammation and TGF-β1/Smad3 signaling pathway.

Renal fibrosis is a key pathological process in the progression of chronic kidney disease (CKD). Panaxatriol saponins (PTS), the main bioactive compounds extracted from Panax notoginseng (Burk.) F.H. Chen, have demonstrated antioxidative and anti-inflammatory activities. This study aimed to investigate the potential protective effects of PTS against renal fibrosis and explore the underlying pharmacological mechanisms. A unilateral ureteral obstruction (UUO) model was established in Sprague-Dawley (SD) rats to induce renal fibrosis. Histopathological changes were assessed using hematoxylin and eosin (HE) staining, Masson's trichrome staining, and transmission electron microscopy (TEM). Network pharmacology and molecular docking approaches were employed to identify potential signaling molecules through which PTS may mitigate renal fibrosis. Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry were utilized to validate the involvement of specific signaling pathways in PTS-mediated anti-fibrotic effects. Our data demonstrated that PTS alleviated renal dysfunction and provided protective effects against renal fibrosis, primarily through the TNF-α and TGF-β1 signaling pathways. Moreover, PTS treatment significantly downregulated pro-inflammatory cytokines such as TNF-α, IL-6, and Smad3 activity. Additionally, PTS inhibited the expression of key fibrosis markers, including α-SMA, collagen I, and fibronectin. Our study suggests that PTS exert a prevention effect in renal fibrosis by blocking the TGF-β1/Smad3 signaling pathway.