1. Withaferin A inhibits apoptosis via activated Akt-mediated inhibition of oxidative stress.
- Author
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Yan Z, Guo R, Gan L, Lau WB, Cao X, Zhao J, Ma X, Christopher TA, Lopez BL, and Wang Y
- Subjects
- Animals, Antioxidants metabolism, Cell Proliferation drug effects, Cells, Cultured, Female, Myocardial Reperfusion Injury metabolism, Myocardial Reperfusion Injury pathology, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Apoptosis drug effects, Gene Expression Regulation drug effects, Myocardial Reperfusion Injury drug therapy, Myocytes, Cardiac drug effects, Oxidative Stress drug effects, Proto-Oncogene Proteins c-akt metabolism, Withanolides pharmacology
- Abstract
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 (H
2 O2 )-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 H2 O2 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
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