Shenqi Xiezhuo Decoction alleviates renal fibrosis in rats by ameliorating oxidative stress and inflammation through the Rap1/MAPK/FoxO3a signaling pathway
LU Xiaoyu
LIU Zhihui
LIU Ye
PANG Tianxiao
BIAN Rong
GUO Ling
HE Xuehong
Abstract：Objective To explore the mechanism of Shenqi Xiezhuo Decoction(SQXZD)for improving renal fibrosis(RF)in rats.Methods The chemical components of SQXZD were identified using UPLC-Q Exactive/MS,and component-disease target network and enrichment analyses were conducted to screen the key pathways and targets.In the animal experiment,49 male SD rats were randomized equally into blank control group,sham operation group,unilateral ureteral obstruction-induced RF model group,losartan treatment(daily dose 4.6 mg/kg)group,and low-,medium-,and high-dose SQXZD(9.7,19.4,and 38.8 g/kg,respectively)treatment groups.After 14 days'treatment,renal pathologies and collagen deposition of the rats were examined with HE and Masson staining,and serum levels of BUN,Cr,SOD,MDA,GSH-px,IL-6,and TNF-α were detected.Western blotting and qRT-PCR were used to detect renal protein and mRNA expressions of α-SMA,Col-I,NAKED2,Rap1,B-raf,Raf-1,MEK3/6,p38MAPK,MEK,ERK1/2,p-ERK1/2,FoxO3a,p-FoxO3a,and MnSOD.Results A total of 263 chemical components were identified in SQXZD.Network pharmacology revealed 170 intersecting targets between the components and RF enriched in the MAPK,Rap1,and FoxO pathways.The rat models of RF showed abnormal renal structural changes,increased fibrosis area,elevated serum BUN,Cr,MDA,IL-6,and TNF-α levels,reduced SOD and GSH-px levels,upregulated renal expressions of α-SMA,Col-I,NAKED2,Rap1,B-raf,MEK,ERK1/2,p-ERK1/2,MEK3/6,and p38MAPK,and downregulated Raf-1,FoxO3a,p-FoxO3a,and MnSOD expressions.Treatment with losartan and SQXZD(especially at the medium dose)obviously lessened renal pathologies,improved renal functions,alleviated oxidative stress and inflammation,and ameliorated abnormal changes in the Rap1/MAPK/FoxO3a signaling pathway in the rat models.Conclusion SQXZD alleviates RF and improves renal function in rats possibly by ameliorating renal oxidative stress and inflammation via regulating the Rap1/MAPK/FoxO3a signaling pathway.
Keywords：Shenqi Xiezhuo Decoctionrenal fibrosisoxidative stressinflammatory factorsRap1/MAPK/FoxO3a signaling pathway
Publication Date：2025-12-20
Online Publishing Date：2025-12-31(First online date of this platform, not the publication date of the document)
Pages：13( 2585-2597 )