Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway.
10.1016/j.joim.2025.07.001
- Author:
Wen-Yan ZHOU
1
;
Jian-Kui DU
2
;
Hong-Hong LIU
3
;
Lei DENG
4
;
Kai MA
5
;
Jian XIAO
6
;
Sheng ZHANG
7
;
Chang-Nan WANG
8
Author Information
1. Department of Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan 750003, Ningxia Hui Autonomous Region, China.
2. Department of Physiology, Navy Medical University, Shanghai 200433, China.
3. Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
4. Department of Emergency, Affiliated Hospital of Chifeng University, Chifeng 024000, Inner Mongolia Autonomous Region, China.
5. Lab of Stress Injury, School of Life Sciences, Shanghai University, Shanghai 200444, China.
6. Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
7. Department of Critical Care Medicine, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
8. Lab of Stress Injury, School of Life Sciences, Shanghai University, Shanghai 200444, China. Electronic address: wangchangnan@shu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Baicalein;
Ferroptosis;
Hypoxia-inducible factor 1 subunit α;
Myocardial injury;
Sepsis;
miR-299b-5p
- MeSH:
Flavanones/pharmacology*;
Animals;
MicroRNAs/genetics*;
Lipopolysaccharides;
Hypoxia-Inducible Factor 1, alpha Subunit/genetics*;
Ferroptosis/drug effects*;
Mice;
Myocytes, Cardiac/metabolism*;
Signal Transduction/drug effects*;
Rats;
Male;
Mice, Inbred C57BL;
Cardiomyopathies/etiology*;
Cell Line;
Sepsis/complications*
- From:
Journal of Integrative Medicine
2025;23(5):560-575
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC).
METHODS:A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.
RESULTS:Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes.
CONCLUSION:Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
