HuangxueYishen Decoction Attenuates Chronic Kidney Disease: Associated with Inhibition of p38 MAPK Pathway Phosphorylation Activation

In clinical practice, Huangxueyishen decoction (HXYS) has been proven effective in treating chronic kidney disease (CKD). Nevertheless, the potential mechanisms remain unclear. The study aims to investigate the protective effect and possible mechanism of HXYS attenuating CKD in rats via pharmacological and proteomic methods. Rats were randomly divided into the Normal control group, CKD Model group, Valsartan group, HXYS-Low, and High dose group. The pharmaceutical efficacy of HXYS was evaluated in terms of 24-hour proteinuria and blood biochemical indexes. Hematoxylin and eosin (H&E) and Masson's trichrome staining (MASSON) were used to observe the renal pathological changes. The Label-free quantitative proteomics was applied to detect differentially expressed proteins (DEPs) and conduct biological function and pathway enrichment analysis. Western blot was used to analyze and validate the protein expression changes. HXYS significantly reduced 24-hour proteinuria (UTP), serum creatinine (SCr), and blood urea nitrogen (BUN) while increasing serum albumin (Alb) (P < 0.01), improving renal function in CKD rats. Histopathological analysis showed reduced tubular damage and fibrosis. The low-dose HXYS group demonstrated the most significant therapeutic effects, delaying CKD progression. 431 differentially expressed proteins (DEPs) were identified, with key changes in oxidative stress, apoptosis, and the mitogen-activated protein kinase (MAPK) signaling pathway regulation. The therapeutic effect of HXYS on CKD is accompanied by the inhibition of the MAPK signaling pathway, including p38, JNK, and ERK phosphorylation. This study confirmed the therapeutic effect of HXYS, screened the potential biomarkers, and verified the possible pathways of action of HXYS.