文献类型：期刊文献

英文题名：Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis

作者：Zhang, Lin[1];Liu, Xiaorui[1];Wang, Juan[1];Li, Zimu[1];Wang, Siqi[1];Yang, Wen[1];Hai, Yang[1,4];Liu, Dongling[1,2,3]

第一作者：张乐;张丽;张雷;张磊;张玲;张立

通信作者：Liu, DL[1];Liu, DL[2];Liu, DL[3]

机构：[1]Gansu Univ Chinese Med, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Gansu Pharmaceut Ind Innovat Res Inst, Lanzhou 730000, Gansu, Peoples R China;[3]Northwest Collaborat Innovat Ctr Tradit Chinese Me, Lanzhou 730000, Peoples R China;[4]Minist Educ, Key Lab Dunhuang Med, Lanzhou, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Pharm, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Gansu Pharmaceut Ind Innovat Res Inst, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), Northwest Collaborat Innovat Ctr Tradit Chinese Me, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：30

期号：1

起止页码：2503130

外文期刊名：REDOX REPORT

收录：;Scopus(收录号：2-s2.0-105005472330);WOS:【SCI-EXPANDED(收录号:WOS:001487466700001)】；

基金：This project was supported by the National Natural Science Foundation of China [grant number 82074419], Gansu Provincial Science and Technology Plan Project [grant number 23JRRA1203 and 23JR6KA028] and Double First-Class Major Scientific Research Project of the Gansu Provincial Department of Education (GSSYLXM-05).

语种：英文

外文关键词：KP; DOX; cardiotoxicity; cardiomyocytes; mitochondrial ROS; ferroptosis; oxidative stress; action mechanism

摘要：BackgroundDoxorubicin (DOX), a widely used chemotherapeutic agent, is limited in clinical application due to its dose-dependent cardiotoxicity. Therefore, it is crucial to explore alternative therapeutic molecules or drugs for mitigating DOX-induced cardiomyopathy (DIC). In this study aimed to explore underlying mechanisms of the cardioprotective effects of Kaempferol (KP) against DIC.MethodsH9c2 cell-based DIC model were established to explore the pharmacological mechanism. The levels of mitochondrial membrane potential, mitochondrial ROS, mitochondrial Fe2+ and lipid peroxidation were detected using JC-1, TMRE, Mito-SOX, Mito-Ferro Green and C11-BODIPY 581/591 probes. Furthermore, Western blot analysis measured the expression of key regulatory proteins, and NRF2-targeting siRNA was transfected into H9c2 cells. The nuclear translocation of NRF2 was assessed by immunofluorescence.ResultsData revealed that KP mitigated DOX-induced mitochondrial damage and ferroptosis via reducing membrane potential, mitochondrial ROS/Fe-2+, and regulating lipid metabolism. Mechanistically, Western blot analysis revealed that KP inhibited DOX-induced ferroptosis by activating NRF2/SLC7A11/GPX4 axis. Moreover, KP promoted the accumulation and nuclear translocation of NRF2 protein.ConclusionThese findings demonstrated that KP protected against DOX-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis. This provides novel insights into KP as a promising drug candidate for cardioprotection.