Ryota Mori
Development Laboratory, SEPTEM-SOKEN Co., Ltd.,
Masamichi Ishigami
Development Laboratory, SEPTEM-SOKEN Co., Ltd.,
Masanori Okada
Development Laboratory, SEPTEM-SOKEN Co., Ltd.,
Hitoshi Masaki
Tokyo University of Technology

[Abstract]
Polymethoxyflavonoids (PMFs), rich contained in particularly peel of citrus, have attracted attention about many usability on living body such as curative properties against diabetes and overweight, whitening ability of skin. PMFs have been also reported about antioxidant properties; however they are regarded no antioxidant effect directly because of non-reduced structure. On the other hand, Keap1-Nrf2 pathway plays an important role in a defense mechanism against oxidative stress in cells. In this study, we focused on Keap1-Nrf2 signaling pathway, and examined the expression and activity of antioxidant protein with cultured keratinocytes. Of PMFs, sinensetin, tangeretin and nobiletin were tested. HaCaT keratinocytes treated with PMFs showed a significant suppression of increase in intracelluar oxidative stress level by hydrogen peroxide. Moreover, HaCaT keratinocytes treated with PMFs were observed nuclear translocation of Nrf2 and exhibited significant increase in gene expression of gamma-glutamylcysteine synthetase (GCS), is the first enzyme of the cellular glutathione (GSH) biosynthetic pathway, and cellular total GSH amount. Thus, it is likely that antioxidant effect of PMFs derives from increase in cellular GSH via Keap1-Nrf2 signaling pathway. Out of PMFs used this study, tangeretion and nobiletin were recognized a higher increase in cellular GSH. It is probable that PMFs are useful as anti-aging material because oxidative stress is believed to involve one of the causes of skin aging.