通过抗肿瘤药物如顺铂引起的急性肾损伤（AKI）是目前没有有效治疗的严重并发症，导致化疗的减少或中断。天然产物或草药逐渐被认为是对顺铂诱导的AKI具有多重靶向、多效性和较少抵抗性的有前途的药剂。在这项研究中，我们研究了从香茅的根茎中提取的天然黄酮类化合物及最聚香，对于实验室内和实验室外的AKI模型的影响。我们首先在小鼠中进行了药代动力学研究，并发现了使用最聚香后的相对稳定的状态和一小部分转化成了最聚激素。我们发现，最聚香（10μM）和最聚激素（10μM）都显著抑制了顺铂对不死近端肾小管上皮细胞系HK-2的损伤。在通过单次顺铂注射（15mg/kg）诱导的AKI小鼠中，口服最聚香（50mg/kg ）不论是在顺铂注射前还是后，都显著改善了肾功能，减轻了肾组织损伤。我们证明了最聚香抑制了顺铂处理的小鼠和HK-2细胞中的氧化应激并诱导自噬，从而增加了小管细胞的存活力并减少了免疫反应以减轻疾病的进展。此外，最聚香的治疗显著改善了体内体外的缺血再灌注性肾损伤。我们得出结论认为，最聚香是治疗各种AKI的一种有前途的天然产物。这项研究对其在保健产品中的推广具有重要意义，并有助于突破顺铂在临床中的限制使用。©2023年作者、上海中药研究所中科院和中国药理学会独家许可。

Acute kidney injury (AKI) caused by anti-tumor drugs, such as cisplatin, is a severe complication with no effective treatment currently, leading to the reduction or discontinuation of chemotherapy. Natural products or herbal medicines are gradually considered as promising agents against cisplatin-induced AKI with the advantages of multi-targeting, multi-effects, and less resistance. In this study, we investigated the effects of kaempferide, a natural flavonoid extracted from the rhizome of Kaempferia galanga, in experimental AKI models in vitro and in vivo. We first conducted pharmacokinetic study in mice and found a relative stable state of kaempferide with a small amount of conversion into kaempferol. We showed that both kaempferide (10 μM) and kaempferol (10 μM) significantly inhibited cisplatin-caused injuries in immortalized proximal tubule epithelial cell line HK-2. In AKI mice induced by injection of a single dose of cisplatin (15 mg/kg), oral administration of kaempferide (50 mg/kg) either before or after cisplatin injection markedly improved renal function, and ameliorated renal tissue damage. We demonstrated that kaempferide inhibited oxidative stress and induced autophagy in cisplatin-treated mice and HK-2 cells, thus increasing tubular cell viability and decreasing immune responses to attenuate the disease progression. In addition, treatment with kaempferide significantly ameliorated ischemia-reperfusion-induced renal injury in vitro and in vivo. We conclude that kaempferide is a promising natural product for treating various AKI. This study has great implications for promotion of its use in healthcare products, and help to break through the limited use of cisplatin in the clinic.© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.