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

Arch Pharm Res. 2011 May;34(5):811-20. doi: 10.1007/s12272-011-0515-3. Epub 2011 Jun 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • 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*
  • RNA, Messenger / metabolism
  • Skin Pigmentation / drug effects
  • Ultraviolet Rays* / adverse effects


  • Antioxidants
  • Dermatologic Agents
  • Enzyme Inhibitors
  • Fungal Proteins
  • Melanins
  • RNA, Messenger
  • Nitric Oxide
  • Catalase
  • NOS2 protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Monophenol Monooxygenase
  • Glutathione
  • Ascorbic Acid