Apigenin alleviates oxidative stress-induced myocardial injury by regulating SIRT1 signaling pathway

被引:30
作者
Xu, Kun [1 ]
Yang, Yao [1 ]
Lan, Ming [1 ]
Wang, Jiannan [1 ]
Liu, Bing [1 ]
Yan, Mingjing [1 ,2 ]
Wang, Hua [1 ]
Li, Wenlin [1 ]
Sun, Shenghui [1 ]
Zhu, Kaiyi [3 ]
Zhang, Xiyue [1 ]
Hei, Mingyan [3 ]
Huang, Xiuqing [1 ]
Dou, Lin [1 ]
Tang, Weiqing [1 ]
He, Qing [1 ]
Li, Jian [1 ]
Shen, Tao [1 ,2 ]
机构
[1] Chinese Acad Med Sci, Beijing Hosp, Inst Geriatr Med, Beijing Inst Geriatr, Beijing 100730, Peoples R China
[2] Peking Univ, Sch Clin Med 5, Beijing 100730, Peoples R China
[3] Capital Med Univ, Beijing Childrens Hosp, Neonatal Ctr, Dept Neonatol, Beijing 100045, Peoples R China
基金
北京市自然科学基金; 中国国家自然科学基金;
关键词
Apigenin; Isoproterenol; Hypoxia; reoxygenation; SIRT1; Oxidative stress; Apoptosis; HEART;
D O I
10.1016/j.ejphar.2023.175584
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Apigenin is a natural flavonoid which is widely found in vegetables and fruits. However, the mechanism apigenin in oxidative stress-induced myocardial injury has not been fully elucidated. We established isoproterenol (Iso)-induced myocardial injury mouse model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell injury model, followed by pretreatment with apigenin to explore its protective effects. Apigenin can significantly alleviate isoproterenol-induced oxidative stress, cell apoptosis and myocardial remodeling in vivo. Apigenin pretreatment can also significantly improve cardiomyocyte morphology, decrease H/R induced oxidative stress, and attenuate cell apoptosis and inflammation in vitro. Further mechanism study revealed that apigenin treatment reversed isoprenaline and H/R-induced decrease of Sirtuin1 (SIRT1). Molecular docking results proved that apigenin can form hydrogen bond with 230 Glu, a key site of SIRT1 activation, indicating that apigenin is an agonist of SIRT1. Moreover, SIRT1 knockdown by siRNA significantly reversed the protective effect of apigenin in H/R-induced myocardial injury. In conclusion, apigenin protects cardiomyocyte function from oxidative stress-induced myocardial injury by modulating SIRT1 signaling pathway, which provides a new potential therapeutic natural compound for the clinical treatment of cardiovascular diseases.
引用
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页数:10
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