Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway.
10.1016/j.joim.2024.09.001
- Author:
Pan ZHAI
1
;
Xiao-Hu OUYANG
1
;
Meng-Ling YANG
1
;
Lan LIN
1
;
Jun-Yi LI
1
;
Yi-Ming LI
2
;
Xiang CHENG
3
;
Rui ZHU
4
;
De-Sheng HU
5
Author Information
1. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
2. Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei Province, China.
3. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.
4. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. Electronic address: zhur@hust.edu.cn.
5. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; China-Russia Medical Research Center for Stress Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. Electronic address: desheng.hu@hust.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
Apoptosis;
Luteolin;
Myocardial ischemia/reperfusion injury;
Network pharmacology;
Oxidative stress;
P53 signaling pathway
- MeSH:
Luteolin/pharmacology*;
Animals;
Myocardial Reperfusion Injury/metabolism*;
Oxidative Stress/drug effects*;
Tumor Suppressor Protein p53/genetics*;
Apoptosis/drug effects*;
Mice;
Signal Transduction/drug effects*;
Male;
Disease Models, Animal;
Mice, Inbred C57BL;
Myocardial Infarction/prevention & control*;
Reactive Oxygen Species/metabolism*
- From:
Journal of Integrative Medicine
2024;22(6):652-664
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:Myocardial ischemia/reperfusion injury (MIRI) is an obstacle to the success of cardiac reperfusion 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 validate 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 elevation in HR-incubated HL1 cells in vitro. Finally, the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model, and both luteolin and the p53 inhibitor pifithrin-α demonstrated a similar therapeutic effect in the MIRI mice.
CONCLUSION:Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway. Please cite this article as: Zhai P, Ouyang XH, Yang ML, Lin L, Li JY, Li YM, Cheng X, Zhu R, Hu DS. Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway. J Integr Med. 2024; 22(6): 652-664.
