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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences Advance Access originally published online on July 8, 2009
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2009 64A(10):1031-1038; doi:10.1093/gerona/glp088
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© The Author 2009. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

Deceleration of Senescence in Normal Human Fibroblasts by Withanone Extracted From Ashwagandha Leaves

Nashi Widodo1,2, Navjot Shah1,3, Didik Priyandoko1,3, Tetsuro Ishii3, Sunil C. Kaul1 and Renu Wadhwa1

1 National Institute of Advanced Industrial Science & Technology (AIST), Tsukuba, Ibaraki, Japan
2 Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Malang, Indonesia
3 Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan

Address correspondence to Renu Wadhwa, PhD, National Institute of Advanced Industrial Science & Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan. Email: renu-wadhwa{at}aist.go.jp


  Abstract

Ashwagandha is an Ayurvedic shrub that forms a common ingredient of health supplements, tonics, and Indian home remedies designed to promote health and quality of life. Though sustained through experience and history, there are only a limited laboratory studies and experimental evidence to its effects. In our efforts to characterize Ashwagandha activities and their molecular mechanisms, we initially prepared leaf extract of Ashwagandha (i-Extract) that showed tumor-inhibitory activity. In the present study, we demonstrate that a major component of i-Extract and withanone (i-Factor) protected the normal human fibroblasts against the toxicity caused by withaferin A. It increased the in vitro division potential of normal human cells that appeared to be mediated by decreased accumulation of molecular damage, downregulation of the senescence-specific β-galactosidase activity and the senescence marker protein, p21WAF-1, protection against oxidative damage, and induction of proteasomal activity. To the best of our knowledge, we provide the first example of phytochemical(s) (i-Extract and withanone) that have both anticancer and antiaging activities and point to the molecular link between aging and cancer.

Keywords Ashwagandha; Extract; Human fibroblasts; Oxidative damage; Proteasomal activity; Senescence

Received: December 8, 2008; Accepted: June 10, 2009

Decision Editor: Huber R. Warner, PhD


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