Artemisinic acid inhibits melanogenesis through downregulation of C/EBP α-dependent expression of HMG-CoA reductase gene.

Jongsung Lee, Jienny Lee, Eunsun Jung, Jae Youl Cho, Deokhoon Park

Department of Dermatological Health Management, College of Health Science, Eulji University, 461-713 Gyeonggi Do, Republic of Korea. jslee@eulji.ac.kr

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2013 Jan

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Cholesterol is associated with the regulation of melanogenesis which is the major physiological defense against solar irradiation. The present study was designed to determine the effects of artemisinic acid on melanogenesis and its mechanisms of action in human epidermal melanocytes. In this study, we found that artemisinic acid inhibited melanin content. The mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were reduced by artemisinic acid treatment. Additionally, the mRNA levels of melanogenesis-related genes (c-KIT, stem cell factor (SCF), and macrophage migration inhibitory factor (MIF)) were down-regulated by artemisinic acid. Furthermore, cAMP production and protein kinase A (PKA) activity were suppressed by artemisinic acid. Moreover, attempts to elucidate a possible mechanism underlying the artemisinic acid-mediated effects revealed that artemisinic acid regulated melanogenesis by inhibiting cholesterol synthesis through downregulation of the hydroxymethylglutaryl CoA (HMG CoA) reductase gene, which was mediated through reduced expression of the CCAAT/enhancer-binding protein (C/EBP) α gene. Taken together, these findings indicate that the inhibition of melanogenesis by artemisinic acid occurs through reduced expression of the HMG CoA reductase gene, which is mediated by C/EBP α inhibition and suggest that artemisinic acid may be useful as a hyperpigmentation inhibitor. Copyright © 2012 Elsevier Ltd. All rights reserved.

Citation

Jongsung Lee, Jienny Lee, Eunsun Jung, Jae Youl Cho, Deokhoon Park. Artemisinic acid inhibits melanogenesis through downregulation of C/EBP α-dependent expression of HMG-CoA reductase gene. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2013 Jan;51:225-30