Uraiwan PanichVanida Tangsupa-A-NanTasanee OnkoksoongKamolratana KongtaphanKanda KasetsinsombatPravit AkarasereenontAdisak WongkajornsilpMahidol University2018-05-032018-05-032011-05-01Archives of Pharmacal Research. Vol.34, No.5 (2011), 811-82019763786025362692-s2.0-79960228052https://repository.li.mahidol.ac.th/handle/20.500.14594/11556Ascorbic acid (AA) has been well known as a skin whitening agent, although attempts have been made to evaluate its protective role against ultraviolet (UV)-induced skin hyperpigmentation or increased melanin production. While melanogenesis is a defense mechanism of the skin against UV irradiation, melanin overproduction may also contribute to melanoma initiation. UVA might play a role in melanogenesis through promoting oxidative stress, which occurs as the result of increased formation of oxidants and/or reactive nitrogen species (RNS) including nitric oxide (NO). Therefore, we investigated the antimelanogenic effect of AA (7.5-120 μM) in association with its inhibitory effect on UVA-induced oxidant formation, NO production through endothelial and inducible NO synthases (eNOS and iNOS) activation and impairment of antioxidant defense using G361 human melanoma cells. Our study demonstrated a comparable ability of AA with that of kojic acid, a well-known tyrosinase inhibitor in inhibiting mushroom tyrosinase. Melanin content was reduced by AA, but neither tyrosinase activity nor mRNA levels were reduced by AA at non-cytotoxic concentrations in UVA-irradiated G361 cells. AA was shown to inhibit UVA-mediated catalase (CAT) inactivation, glutathione (GSH) depletion, oxidant formation and NO production through suppression of eNOS and iNOS mRNA. We report herein that AA can protect against UVA-dependent melanogenesis possibly through the improvement of antioxidant defense capacity and inhibition of NO production through down-regulation of eNOS and iNOS mRNA. © 2011 The Pharmaceutical Society of Korea and Springer Netherlands.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1007/s12272-011-0515-3