Jijun Wu1,
Yingli Zhou2 ,
Ming Guo1,
Jie Yang1,
Feifei Wu1,
Jialin Wang1
1Department of Cardiology, Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, Zhejiang Province 310000, China;
2Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou, Zhejiang Province 310000, China.
For correspondence:- Yingli Zhou
Email: ylzhou5701@163.com Tel:+8657187814481
Accepted: 16 July 2022
Published: 28 August 2022
Citation:
Wu J, Zhou Y, Guo M, Yang J, Wu F, Wang J.
Tectorigenin ameliorates myocardial cell injury caused by hypoxia/reoxygenation by inhibiting autophagy via activation of PI3K/AKT/mTOR pathway. Trop J Pharm Res 2022; 21(8):1601-1606
doi:
10.4314/tjpr.v21i8.4
© 2022 The authors.
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Abstract
Purpose: To investigate the protective role of tectorigenin in myocardial ischaemia/reperfusion.
Methods: Myocardial cells (H9c2) were treated with different concentrations of tectorigenin and exposed to hypoxia/reoxygenation. Cell viability and apoptosis were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) staining, respectively. Oxidative stress and inflammation were evaluated using enzyme-linked immunosorbent assay (ELISA), while autophagy and the underlying mechanisms of action were evaluated by Western blot.
Results: Tectorigenin enhanced the proliferative activity of H9c2 under hypoxia/reoxygenation conditions, and significantly reduced the apoptotic activity (p < 0.001) through decrease in Bax and increase in Bcl-2. Tectorigenin also significantly up-regulated SOD (superoxide dismutase) and GSH (glutathione) levels (p < 0.01), and down-regulated MDA (malondialdehyde) and MPO (myeloperoxidase) in hypoxia/reoxygenation-induced H9c2. TNF-α (tumor necrosis factor-α), IL(interleukin)-1β, and IL-6 levels were also inhibited by tectorigenin by down-regulating p-p65. Hypoxia/reoxygenation-induced increase in p62 and decrease in Beclin-1 and LC3-II/LC3-I were reversed by tectorigenin. Protein expressions of p-mTOR, p-AKT, and p-PI3K in hypoxia/reoxygenation-induced H9c2 were elevated by tectorigenin.
Conclusion: Tectorigenin exerts anti-oxidant, anti-inflammatory, and anti-autophagic effects on hypoxia/reoxygenation-induced H9c2 through the activation of PI3K/AKT/mTOR pathway, thus suggesting that it is a potential agent for the management of myocardial ischaemia/reperfusion.
Keywords: Tectorigenin, Oxidative stress, Inflammation, Autophagy, Hypoxia/reoxygenation, Myocardial cells, PI3K/AKT/mTOR