Anemoside B4 attenuates nephrotoxicity of cisplatin without reducing anti-tumor activity of cisplatin

Cisplatin is a highly effective chemotherapeutic agent commonly used in the treatment of a wide variety of malignancies. However, its clinical usage is severely limited by its serious side effects, especially nephrotoxicity. Anemoside B4, is a major saponins, rich in root of Pulsatilla chinensis (Bunge), has anti-inflammation in vitro. However, the antioxidant or anti-inflammatory effects of anemoside B4 in cisplatin-induced nephrotoxicity have not been clearly demonstrated.In this study, we investigated whether anemoside B4 exhibits protective effects against cisplatin-induced nephrotoxicity involving antioxidant or anti-apoptosis effects.To clarify it, the effects of anemoside B4 on HEK 293 cell viability was measured by CCK8 kits, intracellular antioxidant capacity including glutathione reduced (GSH), catalase (CAT) were estimated using chemical kits, apoptosis rate and intracellular reactive oxygen species (ROS) was analyzed by flow cytometry, apoptosis protein was measured by western blotting. In vivo model of cisplatin-induced mice acute renal failure was performed to evaluate the properties of anemoside B4. Besides, to evaluate the effect of anemoside B4 on the anti-tumor activity of cisplatin, S180 xenograft models were used.Anemoside B4 potently increased cisplatin-treated HEK 293T cells viability on the concentration and time manners and inhibited cells apoptosis, as demonstrated by the decreased cleaved PARP protein expressions. Anemoside B4 decreased reactive oxygen species (ROS) content and improved superoxide dismutase (SOD) activity. In vivo experiment showed that pretreatment with anemoside B4 effectively adjusted body weight and kidney index, and reduced cisplatin-elevated blood urea nitrogen (BUN) and creatinine (CREA) levels, as well as ameliorated the histopathological damage. Further studies showed that anemoside B4 did not reduce antitumor activity of cisplatin in murine S180 cancer xenograft tumor models. In addition, anemoside B4 per set showed low toxicity in mice.The strong antioxidant and anti-apoptosis effects of anemoside B4 may provide therapeutic potential for cisplatin-induced nephrotoxicity without compromising its therapeutic efficiency.