Withaferin A inhibits apoptosis via activated Akt-mediated inhibition of oxidative stress

Withaferin A (WFA), a withanolide derived from medicinal plant Withania somnifera, possesses anti-tumorigenic and immunomodulatory activities against various cancer cells. However, the role of WFA in myocardial ischemia reperfusion (MI/R) injury remains unclear. In the present study, we determined w...

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Bibliographic Details
Published in:Life sciences (1973) 2018-10, Vol.211, p.91-101
Main Authors: Yan, Zheyi, Guo, Rui, Gan, Lu, Lau, Wayne Bond, Cao, Xiaoming, Zhao, Jianli, Ma, Xinliang, Christopher, Theodore A., Lopez, Bernard L., Wang, Yajing
Format: Article
Language:English
Subjects:
Akt
AKT protein
Antioxidant
Antioxidants
Apoptosis
Cancer
Cardiomyocytes
Cardiovascular diseases
Caspase
Caspase-3
Heart
Heart diseases
Herbal medicine
Hydrogen peroxide
Immunomodulation
Injuries
Ischemia
Ischemia/reperfusion
Medicinal plants
Myocardial ischemia
Oxidative stress
Reperfusion
Superoxide dismutase
Withaferin A
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Summary:Withaferin A (WFA), a withanolide derived from medicinal plant Withania somnifera, possesses anti-tumorigenic and immunomodulatory activities against various cancer cells. However, the role of WFA in myocardial ischemia reperfusion (MI/R) injury remains unclear. In the present study, we determined whether WFA may regulate cardiac ischemia reperfusion injury and elucidate the underlying mechanisms. We demonstrated that WFA enhanced H9c2 cells survival ability against simulated ischemia/reperfusion (SI/R) or hydrogen peroxide (H2O2)-induced cell apoptosis. In addition, the enhanced oxidative stress induced by SI/R was inhibited by WFA. Among the multiple antioxidant molecules determined, antioxidants SOD2, SOD3, Prdx-1 was obviously upregulated by WFA. When Akt inhibitor IV was administrated, WFA's suppression effect on oxidative stress was obviously abolished. Additional experiments demonstrated that WFA successfully inhibited H2O2 induced upregulation of SOD2, SOD3, and Prdx-1, ameliorated cardiomyocyte caspase-3 activity via an Akt dependent manner. Collectively, these results support the therapeutic potential of WFA against cardiac ischemia reperfusion injury and highlight the application of WFA in cardiovascular diseases holding great promise for the future.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2018.09.020