Panax notoginseng saponins ameliorate renal interstitial fibrosis in a rat model of chronic kidney disease via the TLR4/NF-?B signaling pathway

Background: Renal interstitial fibrosis (RIF) is a core pathological process in the progression of chronic kidney disease (CKD), but effective therapeutic drugs are currently lacking. Panax notoginseng saponins (PNS) exhibit potential anti-inflammatory and anti-fibrotic effects, yet their mechanism of action in RIF remains unclear. Objectives: This study aims to investigate the ameliorative effects of Panax notoginseng saponins (PNS) on renal interstitial fibrosis in a rat model of chronic kidney disease (CKD) and to elucidate whether these effects are mediated through the regulation of the TLR4/NF-?B signaling pathway. Methods: A rat model of CKD was established, with experimental groups including a healthy control group, a model group, PNS treated group, TAK 242 group, LPS group and combination groups (PNS+TAK 242 and PNS+LPS). Renal pathology and fibrosis were evaluated by HE and Masson staining, while the expression of fibrosis markers and TLR4/NF ?B pathway molecules was analyzed via RT qPCR and Western blot. Results: (1) Compared with the model group, PNS treatment significantly alleviated renal tissue damage and reduced the fibrotic area, while also downregulating the gene and protein expression of fibrosis markers, TLR4 and Rel (which encodes NF-?B p65); (2) he TLR4 inhibitor TAK-242 exhibited anti-fibrotic effects similar to those of PNS and the combination of PNS and TAK-242 yielded the most pronounced therapeutic outcomes. Conclusion: PNS significantly alleviates renal interstitial fibrosis in the CKD model rats and its mechanism is associated with the inhibition of the TLR4/NF-?B signaling pathway, thereby downregulating the expression of downstream pro fibrotic factors.