title: Photoprotection by dietary phenolics against melanogenesis induced by UVA through Nrf2-dependent antioxidant responses.
abstract: Dietary phenolics may play a protective role in UV-mediated skin pigmentation through their antioxidant and UV-absorbing actions. In this study, we investigated whether genetic silencing of Nrf2, regulating the transcription of antioxidant genes, affected melanogenesis in primary human epidermal melanocytes (HEMn) and B16F10 melanoma cells subjected to UVA (8J/cm(2)) exposure. Then, we explored the antimelanogenic actions of phenolics; caffeic acid (CA) and ferulic acid (FA) providing partial UVA protection; quercetin (QU) and rutin (RU) providing strong UVA protection and; avobenzone (AV), an efficient UVA filter, in association with modulation of Nrf2-mediated antioxidant defenses in response to UVA insults in B16F10 cells. Upon oxidative insults, Nrf2 silencing promoted melanogenesis in both HEMn and B16F10 cells irradiated with UVA. Stimulation of melanogenesis by UVA correlated with increased ROS and oxidative DNA damage (8-OHdG), GSH depletion as well as a transient downregulation of Nrf2 nuclear translocation and of Nrf2-ARE signaling in B16F10 cells. All test compounds exerted antimelanogenic effects with respect to their abilities to reverse UVA-mediated oxidative damage as well as downregulation of Nrf2 activity and its target antioxidants (GCLC, GST and NQO1) in B16F10 cells. In conclusion, defective Nrf2 may promote melanogenesis under UVA irradiation through oxidative stress mechanisms. Compounds with antioxidant and/or UVA absorption properties could protect against UVA-induced melanogenesis through indirect regulatory effect on Nrf2-ARE pathway.
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Anyamanee
authors.initials: A
authors.lastname: Chaiprasongsuk
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Tasanee
authors.initials: T
authors.lastname: Onkoksoong
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Thanyawan
authors.initials: T
authors.lastname: Pluemsamran
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors.forename: Saowalak
authors.initials: S
authors.lastname: Limsaengurai
authors.affiliation: Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: uraiwan.pan@mahidol.ac.th.
authors.forename: Uraiwan
authors.initials: U
authors.lastname: Panich
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000494:pharmacology*; D053898:Biosynthetic Pathways / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019587:Dietary Supplements; D055785:Gene Knockdown Techniques; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D008543:Melanins; D051267:NF-E2-Related Factor 2; D010636:Phenols; D020011:Protective Agents; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D014442:Monophenol Monooxygenase; D003849:Deoxyguanosine; D005978:Glutathione
keywords: Antioxidant; Melanogenesis; Nuclear factor E2-related factor 2 (Nrf2); Phenolics; Ultraviolet A