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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.

SUBMITTER: Wu Z

PROVIDER: S-EPMC7444337 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Wu Zhen Z Li Chunfeng C Li Qiang Q Li Jing J Lu Xin X

Experimental and therapeutic medicine 20200729 4

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 <i>Radix puerariae</i>, 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 in ...[more]

PMID: 32855680

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Project description:Puerarin was a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen). In present study effect of puerarin on cisplatin nephrotoxicity was evaluated. Rat model of nephrotoxicity was established by a single intraperitoneal injection of cisplatin (7mg/kg). Puerarin was administrated through caudal vein injection once per day at the dose of 10mg/kg, 30mg/kg and 50mg/kg. Biochemical assays showed that after cisplatin treatment the serum urea and creatinine increased significantly compared with control (P<0.05). Cisplatin treatment significantly increased xanthine oxidase (XO) activity and malondialdehyde (MDA) formation, and significantly decreased the levels and /or activities of enzymatic and non-enzymatic antioxidants (GSH, GPx, GST, GR, SOD, CAT), in the kidney tissues. Renal levels of TNF-α and IL-6, two important inflammatory cytokines, were also upregulated by cisplatin. Histopathological examination indicated that cisplatin treatment resulted in severe necrosis and degeneration, hyaline casts in the tubules, intertubular hemorrhage, congestion and swelling in glomerulus and leukocytes infiltration in the kidney tissues. Western blot results demonstrated that cisplatin increased TLR4 and NF-κB protein expression in the kidney tissues. However, all these changes induced by cisplatin were significantly attenuated by puerarin treatment in dose-dependent manner, which indicated the renal protective effect of puerarin. Cell culture experiments illustrated that puerarin alone treatment concentration-dependently inhibited COLO205 and HeLa tumor cell growth and dose-dependently promoted the antitumor activity of cisplatin in COLO205 and HeLa tumor cells. The promotion effects might be attributed to suppression of cisplatin-increased NF-κB p65 expression by puerarin. Taken together, findings in this study suggested that puerarin exhibited renal protection against cisplatin nephrotoxicity via inhibiting TLR4/NF-κB signaling, with no inhibition but promotion effect on the antitumor activity of cisplatin. Puerarin might be a promising adjuvant agent for cisplatin chemotherapy.

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

Publications

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

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