Novel Furocoumarin Derivatives Stimulate Melanogenesis in B16 Melanoma Cells by Up-Regulation of MITF and TYR Family via Akt/GSK3 beta/beta-Catenin Signaling Pathways
Niu, C (Niu, Chao)[ 1 ]; Yin, L (Yin, Li)[ 1,2 ]; Aisa, HA (Aisa, Haji Akber)[ 1 ]
2018
发表期刊INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN1422-0067
卷号19期号:3页码:1-19
摘要

The extracts of Ficuscarica L. and Psoralen corylifolia L. are traditional Uygur medicines for the treatment of vitiligo, and its active ingredients furocoumarins, were are found to be the most effective agents against this skin disorder nowadays. Therefore, a series of novel easter derivatives (8a-8p) of furocoumarin were designed and synthesized based on our previous research to improve this activity in the present study. The synthesized derivatives were biologically evaluated for melanin synthesis in murine B16 cells and the SAR (structure-activity relationship) was summarized. Eight derivatives were more potent than positive control (8-MOP, 8-methoxypsoralan), especially compounds 8n (200%) and 8o (197%), which were nearly 1.5-fold potency when compared with 8-MOP (136%). Furthermore, the signaling pathway by which 8n activates the melanin biosynthesis was defined. Our results showed that it not only elevated the melanin content, but also stimulated the activity of tyrosinasein a concentration-dependent manner. Increasing of phosphorylation of Akt (also named PKB, protein kinase B) and non-activated GSK3 beta (glycogen synthase kinase 3 beta), which inhibited the degradation of B-catenin were observed through Western blot analysis. The accumulation of beta-catenin probably led to the activation of transcription of MITF (microphthalmia-associated transcription factor) and TYR (tyrosinase) family, as well as the subsequent induction of melanin synthesis.

关键词Vitiligo Furocoumarin Melanogenesis Sar Akt/gsk3 Beta/beta-catenin Signaling Pathways
DOI10.3390/ijms19030746
收录类别SCI
WOS记录号WOS:000428309800103
引用统计
文献类型期刊论文
条目标识符http://ir.xjipc.cas.cn/handle/365002/5618
专题省部共建新疆特有药用资源利用重点实验室
资源化学研究室
通讯作者Aisa, HA (Aisa, Haji Akber)[ 1 ]
作者单位1.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, State Key Lab Basis Xinjiang Indigenous Med Plant, Key Lab Plant Resources & Chem Arid Zone, Urumqi 830011, Peoples R China
2.Univ Chinese Acad Sci, Beijing 101408, Peoples R China
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Niu, C ,Yin, L ,Aisa, HA . Novel Furocoumarin Derivatives Stimulate Melanogenesis in B16 Melanoma Cells by Up-Regulation of MITF and TYR Family via Akt/GSK3 beta/beta-Catenin Signaling Pathways[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2018,19(3):1-19.
APA Niu, C ,Yin, L ,&Aisa, HA .(2018).Novel Furocoumarin Derivatives Stimulate Melanogenesis in B16 Melanoma Cells by Up-Regulation of MITF and TYR Family via Akt/GSK3 beta/beta-Catenin Signaling Pathways.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,19(3),1-19.
MLA Niu, C ,et al."Novel Furocoumarin Derivatives Stimulate Melanogenesis in B16 Melanoma Cells by Up-Regulation of MITF and TYR Family via Akt/GSK3 beta/beta-Catenin Signaling Pathways".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 19.3(2018):1-19.
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