Back to Search
Start Over
Withaferin A inhibits apoptosis via activated Akt-mediated inhibition of oxidative stress.
- Source :
-
Life sciences [Life Sci] 2018 Oct 15; Vol. 211, pp. 91-101. Date of Electronic Publication: 2018 Sep 10. - Publication Year :
- 2018
-
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 <subscript>2</subscript> O <subscript>2</subscript> )-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 H <subscript>2</subscript> O <subscript>2</subscript> 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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 211
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 30213729
- Full Text :
- https://doi.org/10.1016/j.lfs.2018.09.020