Deceleration of senescence in normal human fibroblasts by withanone extracted from ashwagandha leaves.
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 beta-galactosidase activity and the senescence marker protein, p21(WAF-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.
Widodo
Nashi
N
National Institute of Advanced Industrial Science & Technology, Tsukuba, Ibaraki, Japan.
Shah
Navjot
N
Priyandoko
Didik
D
Ishii
Tetsuro
T
Kaul
Sunil C
SC
Wadhwa
Renu
R
D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018929:Cell Culture Techniques; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D032341:Withania; D054358:Withanolides / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C493956:CDKN1A protein, human; C539004:CDKN2AIP protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010936:Plant Extracts; D016601:RNA-Binding Proteins; D054358:Withanolides; D001616:beta-Galactosidase; D046988:Proteasome Endopeptidase Complex; C030693:Ashwagandha