Ethanolic extract of Melia azedarach L. induces melanogenesis through the cAMP-PKA-CREB signaling pathway

被引：6

作者：

Kim, Mi-Ok ^{[1
,2
]}

Park, Se Jung ^{[1
,2
]}

Park, See-Hyoung ^{[3
]}

Oh, Sae Woong ^{[1
,2
]}

Lee, Seung Eun ^{[1
,2
]}

Yoo, Ju Ah ^{[1
,2
]}

Kwon, Kitae ^{[1
,2
]}

Kim, Jangsoon ^{[1
,2
]}

Kim, Min Hee ^{[4
]}

Cho, Jae Youl ^{[5
]}

Lee, Jongsung ^{[1
,2
]}

机构：

[1] Sungkyunkwan Univ, Dept Integrat Biotechnol, Coll Biotechnol & Bioengn, Mol Dermatol Lab, Suwon 16419, Gyeonggi Do, South Korea

[2] Sungkyunkwan Univ, Dept Integrat Biotechnol, Coll Biotechnol & Bioengn, Biocosmet Res Ctr, Suwon 16419, Gyeonggi Do, South Korea

[3] Hongik Univ, Dept Bio & Chem Engn, Sejong 30016, South Korea

[4] Eulji Univ, Dept Phys Therapy, Coll Hlth Sci, Seongnam 13135, Gyeonggi Do, South Korea

[5] Sungkyunkwan Univ, Dept Integrat Biotechnol, Coll Biotechnol & Bioengn, Mol Immunol Lab, Suwon 16419, Gyeonggi Do, South Korea

来源：

MOLECULAR & CELLULAR TOXICOLOGY | 2019年 / 15卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Ethanolic extract of Melia azedarach L; (MAE); Melanin; cAMP; PKA; CREB; VITILIGO; TYROSINASE; ACTIVATION; RESPONSES; MITF;

D O I：

10.1007/s13273-019-0009-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

BackgroundsSince the cause of hypopigmentary skin disorders (hair graying and vitiligo) is typically unknown, there is no known cure for these disorders. Melia azedarach L. is used in Southeast Asia across China and Japan as a traditional medicine, and it has been reported to have various pharmacological properties. However, there have been no reports to demonstrate the involvement of M. azedarach L. in pigmentation. This study was conducted to investigate the effect of ethanolic extract of M. azedarach L. (MAE) on melanogenesis and to elucidate its mechanism of action in B16F10 mouse melanoma cells and human epidermal melanocytes.MethodsEffects of MAE on melanogenesis and its mechanism of action were investigated using several assays, including melanin content, cellular tyrosinase activity, real-time PCR analysis, Western blot analysis, and ELISAs for cyclic AMP (cAMP), protein kinase A (PKA), cAMP response element binding (CREB) protein, and mitogen-activated protein kinases (MAPKs).ResultsMAE increased the melanin content levels and cellular tyrosinase activity in B16F10 mouse melanoma cells and human epidermal melanocytes. In addition, the action mechanism of MAE-induced melanogenesis was examined in human epidermal melanocytes. It also upregulated the expressions of microphthalmia-associated transcription factor (MITF) gene and its downstream target genes, tyrosinase and tyrosinase-related protein (TRP) 1, but not TRP 2. MAE treatment increased the cAMP levels, PKA activity, and phosphorylation of CREB protein, its downstream signaling protein. However, MAE showed no effects on MAPKs (p42/44 MAPK, p38 MAPK, and c-Jun-N-terminal kinase (JNK)).ConclusionThese findings indicate that MAE induces melanogenesis by upregulating the MITF gene through the cAMP-PKA-CREB signaling pathway, and they suggest its potential in the treatment of hypopigmentary skin diseases.

引用

页码：75 / 83

页数：9