Abstract
Objective:Myocardial ischemia/reperfusion injury(MIRI)is an obstacle to the success of cardiac reperfu-sion therapy.This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.Methods:Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery,and administered luteolin.The myocardial infarct size,myocardial enzyme levels,and cardiac function were measured.Latent targets and signaling pathways were screened using network pharmacology and molecular docking.Then,proteins related to the p53 signaling pathway,apoptosis and oxidative stress were measured.Hypoxia/reoxygenation(HR)-incubated HL1 cells were used to val-idate the effects of luteolin in vitro.In addition,a p53 agonist and an inhibitor were used to investigate the mechanism.Results:Luteolin reduced the myocardial infarcted size and myocardial enzymes,and restored cardiac function in MIRI mice.Network pharmacology identified p53 as a hub target.The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties.Additionally,luteolin halted the activation of p53,and prevented both apoptosis and oxidative stress in myocardial tissue in vivo.Furthermore,luteolin inhibited cell apoptosis,JC-1 monomer formation,and reactive oxygen species ele-vation in HR-incubated HL1 cells in vitro.Finally,the p53 agonist NSC319726 downregulated the protec-tive attributes of luteolin in the MIRI mouse model,and both luteolin and the p53 inhibitor pifithrin-αdemonstrated a similar therapeutic effect in the MIRI mice.Conclusion:Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apop-tosis and oxidative stress through its targeting of the p53 signaling pathway.
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