急性肾损伤
药理学
氧化应激
细胞凋亡
体内
肾缺血
肾
炎症
程序性细胞死亡
顺铂
缺氧(环境)
医学
缺血
再灌注损伤
化学
癌症研究
生物
免疫学
生物化学
内科学
化疗
氧气
有机化学
生物技术
作者
Run-run Shan,Ju-tao Yu,Shaofei Zhang,Manman Xie,Rui Hou,Chun-Ya Xie,Ze-hui Dong,Qin Yang,Xiaowei Hu,Yuhang Dong,Yao Zhang,Xiu-Feng Luo,Zong-Yu Cui,Xiaoying Li,Yunchang Xie,Jiagen Wen,Mingming Liu,Juan Jin,Qi Chen,Xiao‐Ming Meng
出处
期刊:Phytomedicine
[Elsevier]
日期:2024-01-01
卷期号:123: 155252-155252
标识
DOI:10.1016/j.phymed.2023.155252
摘要
Acute kidney injury (AKI) has high morbidity and mortality, which is manifested by inflammation and apoptosis. Effective treatment methods for AKI are currently lacking.This study demonstrated the protecting effects of Madecassoside (MA) in the cisplatin- and hypoxia-reoxygenation-induced renal tubular epithelial cells in vitro and AKI mice in vivo.In vivo AKI mouse models were established by inducing them with cisplatin and renal ischemia-reperfusion. In vitro injury models of mouse renal tubular epithelial cells were established by inducing them with cisplatin and hypoxia and reoxygenation, respectively. The mechanism of MA effects was further explored using molecular docking and RNA-sequencing.MA could significantly reduce kidney injury in the cisplatin-and renal ischemia-reperfusion (IRI)-induced AKI. Further validation in the two cellular models also showed that MA had protect effects. MA can alleviate AKI in vitro and in vivo by inhibiting inflammation, cell apoptosis, and oxidative stress. MA exhibited high permeability across the Caco-2 cell, can enter cells directly. Through RNA-seq and molecular docking analysis, this study further demonstrated that MA inhibits its activity by directly binding to JNK kinase, thereby inhibiting c-JUN mediated cell apoptosis and improving AKI. In addition, MA has better renal protective effects compared to curcumin and JNK inhibitor SP600125.The results demonstrate that MA might be a potential drug for the treatment of AKI and act through the JNK/c-JUN signaling pathway.
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