Cisplatin, a proven effective chemotherapeutic agent, has been used clinically to treat malignant solid tumors, whereas its clinical use is limited by serious side effect including nephrotoxicity. Platycodin D (PD), the major and marked saponin isolated from Platycodon grandiflorum, possesses many pharmacological effects. In this study, we evaluated its protective effect against cisplatin‐induced human embryonic kidney 293 (HEK‐293) cells injury and elucidated the related mechanisms. Our results showed that PD (0.25, 0.5, and 1 μM) can dose‐dependently alleviate oxidative stress by decreasing malondialdehyde and reactive oxygen species, while increasing the levels of glutathione, superoxide dismutase, and catalase. Moreover, the elevation of apoptosis including Bax, Bad, cleaved caspase‐3,‐9, and decreased protein levels of Bcl‐2, Bcl‐XL induced by cisplatin were reversed after PD treatment. Importantly, PD pretreatment can also regulate PI3K/Akt and ERK/JNK/p38 signaling pathways. Furthermore, PD was found to reduce NF‐κB‐mediated inflammatory relative proteins. Our finding indicated that PD exerted significant effects on cisplatin induced oxidative stress, apoptosis and inflammatory, which will provide evidence for the development of PD to attenuate cisplatin‐induced nephrotoxicity.

中文翻译：

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Platycodin D通过抑制HEK-293细胞中ROS介导的氧化损伤，凋亡和炎症来抑制顺铂诱导的细胞毒性。

顺铂是一种行之有效的化学治疗药物，已在临床上用于治疗恶性实体瘤，而其临床应用受到包括肾毒性在内的严重副作用的限制。桔梗D（PD），从桔梗中分离得到的主要和标记的皂苷，具有许多药理作用。在这项研究中，我们评估了其对顺铂诱导的人类胚胎肾293（HEK-293）细胞损伤的保护作用，并阐明了相关机制。我们的结果表明，PD（0.25、0.5和1μM）可以通过减少丙二醛和活性氧的种类而剂量依赖性地缓解氧化应激，同时增加谷胱甘肽，超氧化物歧化酶和过氧化氢酶的水平。此外，PD治疗后，细胞凋亡的升高（包括Bax，Bad，裂解的caspase-3，-9和顺铂诱导的Bcl-2，Bcl-XL蛋白质水平降低）得以逆转。重要的是，PD预处理还可以调节PI3K / Akt和ERK / JNK / p38信号通路。此外，发现PD可以减少NF-κB介导的炎症相关蛋白。