PMID:23063590

Citation	Lee, J, Lee, J, Jung, E, Cho, JY and Park, D' (2012) Artemisinic acid inhibits melanogenesis through downregulation of C/EBP α-dependent expression of HMG-CoA reductase gene. Food Chem. Toxicol. '
Abstract	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 aremisinic acid may be useful as a hyperpigmentation inhibitor.
Links	PubMed Online version:10.1016/j.fct.2012.10.002
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:HMDH		GO:0006695: cholesterol biosynthetic process	ECO:0000314:		P		Figure 3 shows artemisinic acid treatment reduces HMG-CoA reductase amounts at the RNA and protein levels, and it causes a reduction in cholesterol synthesis; this suggests that HMG-CoA reductase plays a part in the cholesterol biosynthetic process	complete CACAO 5575
HUMAN:HMDH		GO:0045541: negative regulation of cholesterol biosynthetic process	ECO:0000314:		P		Figure 3: Artemisinic acid inhibits cholesterol synthesis by downregulating the hydroxymethylglutaryl CoA (HMG CoA) reductase gene.	complete CACAO 5357
HUMAN:HMDH	involved_in	GO:0006695: cholesterol biosynthetic process	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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