Although the protective effect of ginsenoside on cisplatin-induced renal injury has been extensively studied, whether ginsenoside interferes with the antitumor effect of cisplatin has not been confirmed. In this paper, we verified the main molecular mechanism of 20(R)-ginsenoside Rg3 (R-Rg3) antagonizing cisplatin-induced acute kidney injury (AKI) through the combination of in vivo and in vitro models. It is worth mentioning that the two cell models of HK-2 and HepG2 were used simultaneously for the first time to explore the effect of the activation site of tumor-associated protein p53 on apoptosis and tumor suppression. The results showed that a single injection of cisplatin (20 mg/kg) led to weight loss, the kidney index of the mice increased, and creatinine (CRE) and blood urea nitrogen (BUN) levels in mice sharply increased. Continuous administration of R-Rg3 at doses of 10 and 20 mg/kg for 10 days could significantly alleviate this symptom. Similarly, R-Rg3 treatment reduced oxidative stress damage caused by cisplatin. Moreover, R-Rg3 could observably reduce the apoptosis and inflammatory infiltration of renal tubular cells induced by cisplatin. We used western blotting analysis to demonstrate that R-Rg3 restored cisplatin-induced AKI might be related to PI3K/AKT and NF-[Formula: see text]B mediated apoptosis and inflammation pathways. In the meantime, we also verified that R-Rg3 could activate different sites of p53 to control renal cell apoptosis induced by cisplatin without affecting its antitumor effect.
Keywords: 20(R)-Ginsenoside Rg3; Acute Kidney Injury; Apoptosis; Cisplatin; NF-[Formula: see text]B; PI3K/AKT.