Effect of salidroside on ferroptosis in myocardial cell injury induced by doxorubicin and the mechanism of Nrf2/HO-1 signaling pathway
ZHANG Yongjie
WANG Xing
ZHANG Minglei
QI Guibin
ZHANG Zhiliang
GAO Jianbu
Abstract：Objective To explore the protective effect of salidroside on doxorubicin-induced myocardial cell injury and its impact on ferroptosis and the nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling path-way.Methods The human cardiomyocyte AC16 cell lines were selected and divided into the control group(normal culture),the model group(1 μmol/L doxorubicin treatment),the salidroside group(1 μmol/L doxorubicin plus 100 μmol/L salidroside treatment),and the inhibitor group(1 μmol/L doxorubicin plus 100 μmol/L salidroside plus 10 μmol/L Nrf2 inhibitor ML385 treatment).Cell viability was assessed using the CCK-8 assay.Intracellular iron ion content was measured using an iron ion de-tection kit.The level of malondialdehyde(MDA)in cells was determined using a MDA detection kit.Reactive oxygen species(ROS)levels in cells were detected using flow cytometry.Western blot and qPCR were used to measure the protein and mRNA expression levels of Nrf2,HO-1,glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and Kelch-like ECH-associated protein 1(Keap1)in cells.Results(1)The cell viability,iron ion content,MDA content,and ROS fluores-cence intensity in the four groups showed statistically significant differences(F=24.788,18.940,39.366,5.767,all P＜0.05).The cell viability in the salidroside group((80.35±10.68)%)was higher than that in the model group((50.32±12.32)%)and the inhib-itor group((61.26±8.65)%)(both P＜0.05);the iron ion content,MDA content and ROS fluorescence intensity in the salidroside group were lower than those in the model group and the inhibitor group(all P＜0.05).(2)PCR results showed that the mRNA levels of HO-1,GPX4,SLC7A11 and Keap1 in the four groups were all statistically significant different(F=48.107,23.978,53.938,127.176,all P＜0.001).The mRNA levels of HO-1,GPX4 and SLC7A11 in the salidroside group were higher than those in the model group and the inhibitor groups(all P＜0.05),while the mRNA level of Keap1 in the salidroside group was lower than that in the model group and the inhibitor group(both P＜0.05).(3)Western blot results showed that the protein expression levels of Nrf2,HO-1,GPX4,SLC7A11 and Keap1 in the four groups were all statistically significant different(F=730.392,596.727,147.094,106.472,131.976,all P＜0.05).The protein expression levels of Nrf2,HO-1,GPX4 and SLC7A11 in the salidroside group were higher than those in the model group(all P＜0.05),and the protein expression level of Keap1 was lower than that in the model group(P＜0.05).The protein expression levels of Nrf2,HO-1 and SLC7A11 in the inhibitor group were lower than those in the salidroside group(all P＜0.05),while the protein expression level of Keap1 was higher than that in the salidroside group(P＜0.05).Conclusion Salidroside can effectively reduce doxorubicin-induced myocardial cell injury,improve cell via-bility,and inhibit ferroptosis-related indicators.
Keywords：salidrosidedoxorubicincardiomyocytesferroptosisnuclear factor-erythroid 2-related factor 2heme oxygenase-1
Publication Date：2025-12-25
Online Publishing Date：2026-01-07(First online date of this platform, not the publication date of the document)
Pages：5( 1599-1603 )