Puerarin alleviates cisplatin-induced acute renal damage and upregulates microRNA-31-related signaling.

Abstract

Cisplatin (DDP) is a commonly used chemotherapy drug; however, the side effects associated with its use, particularly acute kidney injury (AKI), limit its clinical application. Puerarin is a natural flavonoid extracted from the Chinese medical herb Radix puerariae, which has been reported to alleviate DDP-induced nephrotoxicity. However, the mechanisms underlying puerarin regulation on microRNA (miR)-31-mediated signaling pathways in AKI remain unknown. Thus, the present study aimed to investigate the function of puerarin in a DDP-induced AKI rat model via reverse transcription-quantitative PCR and western blot analyses. The results demonstrated that DDP upregulated the levels of miR-31 in a concentration-dependent manner, both in vitro and in vivo. Furthermore, DDP significantly increased blood urea nitrogen and malondialdehyde content, serum creatinine and histopathological changes, while significantly decreasing the expression levels of superoxide dismutase, catalase and glutathione S-transferase in kidney tissues. TUNEL and western blot analyses indicated that DDP increased the expression levels of apoptotic proteins and affected the Numb/Notch1 signaling pathway, which is downstream of miR-31. The effects induced by DDP were counteracted following treatment with puerarin. Taken together, the results of the present study suggest that puerarin exhibits a renal protective effect against DDP-induced AKI by upregulating miR-31 expression and inhibiting the Numb/Notch1 signaling pathway.