The mechanisms underlying the anti-aging activity of the Chinese prescription Kangen-karyu in hydrogen peroxide-induced human fibroblasts.
Our previous study showed that Kangen-karyu extract protected against cellular senescence by reducing oxidative damage through the inhibition of reactive oxygen species generation and regulation of the antioxidative status. Although these findings suggest that Kangen-karyu could delay the aging process, the mechanisms responsible for protection against aging have rarely been elucidated. Therefore, this study was focussed on the mechanisms responsible for the anti-aging activity of Kangen-karyu extract using hydrogen peroxide (H(2)O(2))-induced human diploid fibroblasts, a well-established experimental model of cellular aging. Kangen-karyu extract exerted a protective effect against the morphological changes induced by H(2)O(2) treatment and inhibited senescence-associated beta-galactosidase activity. In addition, the beneficial effects of Kangen-karyu extract on cell viability and lifespan indicated that Kangen-karyu extract could delay the cellular aging process. The observation that Kangen-karyu extract prevented nuclear factor kappa B (NF-kappaB) translocation in response to oxidative stress suggested that Kangen-karyu exerted its anti-aging effect through NF-kappaB modulation and prevention of H(2)O(2)-induced overexpression of haem oxygenase-1 protein. Moreover, pretreatment with Kangen-karyu extract reduced overexpression of bax protein and prevented the mitochondrial membrane potential decline, suggesting that Kangen-karyu extract may protect mitochondria from mitochondrial oxidative stress and dysfunction. These findings indicate that Kangen-karyu is a promising potential anti-aging agent that may delay, or normalize, the aging process by virtue of its protective activity against oxidative stress-related conditions.
Satoh
Akiko
A
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Yokozawa
Takako
T
Kim
Young Ae
YA
Cho
Eun Ju
EJ
Okamoto
Takuya
T
Sei
Yasuo
Y
D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D053630:Depsides; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D001572:Benzofurans; D053630:Depsides; D004365:Drugs, Chinese Herbal; C468270:Kangen-karyu; D016328:NF-kappa B; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; C046833:lithospermic acid; D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1