A novel synthetic Piper amide derivative NED-180 inhibits hyperpigmentation by activating the PI3K and ERK pathways and by regulating Ca2+ influx via TRPM1 channels
- Authors
- Hwang, Eunson; Lee, Taek Hwan; Lee, Wook-Joo; Shim, Won-Sik; Yeo, Eui-Ju; Kim, Sanghee; Kim, Sun Yeou
- Issue Date
- Jan-2016
- Publisher
- WILEY
- Keywords
- Piper amides; melanogenesis; TRPM1; skin lightening agent
- Citation
- PIGMENT CELL & MELANOMA RESEARCH, v.29, no.1, pp.81 - 91
- Journal Title
- PIGMENT CELL & MELANOMA RESEARCH
- Volume
- 29
- Number
- 1
- Start Page
- 81
- End Page
- 91
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8695
- DOI
- 10.1111/pcmr.12430
- ISSN
- 1755-1471
- Abstract
- Piper amides have a characteristic, unsaturated amide group and exhibit diverse biological activities, including proliferation and differentiation of melanocytes, although the molecular mechanisms underlying its antimelanogenesis effect remain unknown. We screened a selected chemical library of newly synthesized Piper amide derivatives and identified (E)-3-(4-(tert-butyl) phenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl) acrylamide (NED-180) as one of the most potent compounds in suppressing melanogenesis. In murine melan-a melanocytes, NED-180 downregulated the expression of melanogenic regulatory proteins including tyrosinase, Tyrp1, Dct, and MITF. PI3K/ Akt-dependent phosphorylation of GSK3b by NED-180 decreases MITF phosphorylation and inhibits melanogenesis without any effects on cytotoxicity and proliferation. Furthermore, topical application of NED-180 significantly ameliorated UVB-induced skin hyperpigmentation in guinea pigs. Interestingly, data obtained using calcium imaging techniques suggested that NED-180 reduced the TPA-induced activation of TRPM1 (melastatin), which could explain the NED-180-induced inhibition of melanogenesis. All things taken together, NED-180 triggers activation of multiple pathways, such as PI3K and ERK, and inhibits TRPM1/TRPV1, leading to inhibition of melanogenesis.
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Collections - 의과대학 > 의예과 > 1. Journal Articles
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