title: Hydrolyzed Methylhesperidin Induces Antioxidant Enzyme Expression via the Nrf2-ARE Pathway in Normal Human Epidermal Keratinocytes.
abstract: Methylhesperidin (MHES) is a mixture of methylated derivatives of the citrus flavonoid hesperidin and is used as a food or pharmaceutical additive. Dietary MHES could be hydrolyzed by gut microflora to give aglycons. Therefore, we prepared hydrolyzed methylhesperidin (h-MHES) and assessed its pharmacological activity in human epidermal keratinocytes. h-MHES promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and the expression of cytoprotective genes (e.g., heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic subunit (GCLC)). h-MHES also increased intracellular glutathione levels and reduced UVB-induced reactive oxygen species. Moreover, h-MHES increased phosphorylation of p38 mitogen-activated protein kinase (MAPK), and a p38 MAPK inhibitor significantly attenuated h-MHES-induced HO-1 and GCLC expression. Furthermore, when we purified the components of h-MHES, we identified two methoxy-chalcones as novel Nrf2 activators. Our study demonstrates that h-MHES can induce cytoprotective gene expression and reduce oxidative stress via the Nrf2-ARE pathway in keratinocytes, suggesting that MHES may contribute to the suppression of UVB-induced skin damage in vivo.
authors: Biological Science Research, Kao Corporation , 2606 Akabane, Ichikai-machi, Haga-gun, Tochigi 321-3497, Japan.
authors: Tetsuya
authors: T
authors: Kuwano
authors: Biological Science Research, Kao Corporation , 2606 Akabane, Ichikai-machi, Haga-gun, Tochigi 321-3497, Japan.
authors: Manabu
authors: M
authors: Watanabe
authors: Biological Science Research, Kao Corporation , 2606 Akabane, Ichikai-machi, Haga-gun, Tochigi 321-3497, Japan.
authors: Daiji
authors: D
authors: Kagawa
authors: Biological Science Research, Kao Corporation , 2606 Akabane, Ichikai-machi, Haga-gun, Tochigi 321-3497, Japan.
authors: Takatoshi
authors: T
authors: Murase
mesh_terms: D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D006569:Hesperidin; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; C052037:methyl hesperidin
keywords: Nrf2; UVB; aglycon; keratinocyte; methylhesperidin