Inhibition of UVA-mediated melanogenesis by ascorbic acid through modulation of antioxidant defense and nitric oxide system

• Published in: Archives of pharmacal research Vol. 34; no. 5; pp. 811 - 820
• Main Authors: Panich, Uraiwan, Tangsupa-a-nan, Vanida, Onkoksoong, Tasanee, Kongtaphan, Kamolratana, Kasetsinsombat, Kanda, Akarasereenont, Pravit, Wongkajornsilp, Adisak
• Format: Journal Article
• Language: English
• Published: Heidelberg Pharmaceutical Society of Korea 01-05-2011; 대한약학회
• Subjects: Antioxidants - pharmacology; Ascorbic Acid - pharmacology; Catalase - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - radiation effects; Dermatologic Agents - pharmacology; Enzyme Inhibitors - metabolism; Fungal Proteins - antagonists & inhibitors; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - radiation effects; Glutathione - metabolism; Humans; Medicine; Melanins - metabolism; Melanocytes - drug effects; Melanocytes - metabolism; Melanocytes - radiation effects; Melanoma - prevention & control; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - genetics; Monophenol Monooxygenase - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Oxidative Stress - drug effects; Pharmacology/Toxicology; Pharmacy; RNA, Messenger - metabolism; Skin Pigmentation - drug effects; Ultraviolet Rays - adverse effects; 약학; Ascorbic acid; Melanogenesis; Ultraviolet A; Nitric oxide; Antioxidant defense
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-011-0515-3

Ascorbic 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.