A famous rhizoma dioscoreae herbal formula (Wubi Shanyao pill) delays renal aging in natural aging mice

Background Renal aging is particularly important in systemic organ injuries caused by aging, characterized by the accumulation of p53 and the consequent cell cycle arrest and apoptosis. Wubi Shanyao pills (WBSY), a classic formula based on traditional Chinese medicine theory, have been widely used to treat patients with spleen-kidney deficiency for centuries. In this study, we investigated the retarding effect of WBSY on kidney natural aging process and its possible molecular mechanisms. Objective This study aimed to evaluate the efficacy of WBSY in delaying the natural aging process of kidneys and to elucidate the underlying molecular mechanisms involving the p53 signaling pathway. Methods We treated the natural aging BALB/c mice by intragastrical administration of WBSY (0.375, 0.75 and 1.5 g/kg/d) for 10 weeks and investigated the effect of WBSY on aging symptoms and renal function. In addition, the detection of senescence and injure in mouse kidneys via hematoxylin and eosin (H&E), immunofluorescence (IF), senescence-associated β-galactosidase (SA-β-Gal) and TdT-mediated dUTP nick end labeling (TUNEL) staining. Finally, by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) staining and western blotting (WB), we examined the expression levels of senescence-associated biomarkers and p53 signaling pathways (including the cell cycle and apoptosis pathways) in the kidneys of mice. Results The findings showed that treatment of WBSY significantly improved the aging-induced physiological changes and renal injury in aging mice. Meanwhile, WBSY treatment delayed telomere shortening as well as down regulated the positive expression of β-galactosidase, phosphorylated histone H2AX (γ-H2AX), p16 and p19 in the kidney tissues. Furthermore, mechanistic investigations revealed that WBSY treatment reduced p53 expression at both the transcriptional and translational levels, thereby down-regulating its downstream p21, Bcl-2 associated X (Bax) and Caspase-3 expression, while up-regulating cyclin dependent kinase 2 (CDK2), retinoblastoma (Rb) and B-cell lymphoma-2 (Bcl-2) expression. Conclusion Taken together, WBSY inhibited factors related to aging, cell cycle and apoptosis, and ameliorated kidney aging in naturally aged mice.