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

作者：Lee Jongsung; Lee Jienny; Jung Eunsun; Cho Jae Youl; Park Deokhoon

来源：Food and Chemical Toxicology, 2013, 51: 225-230.

DOI：10.1016/j.fct.2012.10.002

• Melanogenesis
• Cholesterol
• C/EBP alpha
• HMG CoA reductase
• Artemisinic acid

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 downregulated by artemisinic acid. Furthermore, cAMP production and protein kinase A (PI(A) 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) alpha gene. %26lt;br%26gt;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 alpha inhibition and suggest that artemisinic acid may be useful as a hyperpigmentation inhibitor.

• 出版日期2013-1