title: Inhibition of melanogenesis by jineol from Scolopendra subspinipes mutilans via MAP-Kinase mediated MITF downregulation and the proteasomal degradation of tyrosinase.
abstract: In this study, the authors investigated the anti-melanogenic effects of 3,8-dihydroxyquinoline (jineol) isolated from Scolopendra subspinipes mutilans, the mechanisms responsible for its inhibition of melanogenesis in melan-a cells, and its antioxidant efficacy. Mushroom tyrosinase activities and melanin contents were determined in melan-a cells, and the protein and mRNA levels of MITF, tyrosinase, TYRP-1, and TYRP-2 were assessed. Jineol exhibited significant, concentration-dependent antioxidant effects as determined by DPPH, ABTS, CUPRAC, and FRAP assays. Jineol significantly inhibited mushroom tyrosinase activity by functioning as an uncompetitive inhibitor, and markedly inhibited melanin production and intracellular tyrosinase activity in melan-a cells. In addition, jineol abolished the expressions of tyrosinase, TYRP-1, TYRP-2, and MITF, thereby blocking melanin production and interfering with the phosphorylations of ERK1/2 and p38. Furthermore, specific inhibitors of ERK1/2 and p38 prevented melanogenesis inhibition by jineol, and the proteasome inhibitor (MG-132) prevented jineol-induced reductions in cellular tyrosinase levels. Taken together, jineol was found to stimulate MAP-kinase (ERK1/2 and p38) phosphorylation and the proteolytic degradation pathway, which led to the degradations of MITF and tyrosinase, and to suppress the productions of melanin.
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Md Badrul
authors.initials: MB
authors.lastname: Alam
authors.affiliation: Department of Applied Microbiology and Biotechnology, Microbiome Laboratory, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Bajpai
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
authors.forename: JungIn
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Peijun
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Byeon
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Jeong-Sic
authors.initials: JS
authors.lastname: Ra
authors.affiliation: Department of Biological Sciences, Macquarie University, Sydney, NSW 2109, Australia.|Bio-security and Food Safety, NSW Department of Primary Industries, Elizabeth Macarthur Agricultural Institute (EMAI), Menangle, NSW 2567, Australia.
authors.forename: Rajib
authors.initials: R
authors.lastname: Majumder
authors.affiliation: Kcellbio, Seoulsoop Kolon Digital Tower, Seongsuil-ro-4-gil, Seongdong-gu 04713, Seoul, Korea.
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Kcellbio, Seoulsoop Kolon Digital Tower, Seongsuil-ro-4-gil, Seongdong-gu 04713, Seoul, Korea.
authors.forename: Jung-In
authors.initials: JI
authors.lastname: Yoon
authors.affiliation: Department of Applied Microbiology and Biotechnology, Microbiome Laboratory, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
authors.forename: Irfan A
authors.initials: IA
authors.lastname: Rather
authors.affiliation: Department of Applied Microbiology and Biotechnology, Microbiome Laboratory, Yeungnam University, Gyeongsan, Gyeongbuk 38541, Korea.
authors.forename: Yong-Ha
authors.initials: YH
authors.lastname: Park
authors.affiliation: Division of Biotechnology, College of Environmental and Bioresource Sciences, Chonbuk National University, 79 Gobong-ro, Iksan-si 570-752, Jeonbuk, Republic of Korea.
authors.forename: Kangmin
authors.initials: K
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon 34134, Korea.
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Kyungpook National University, Daegu 41566, Korea.
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001181:Arthropods / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008543:Melanins / Q000096:biosynthesis / Q000235:genetics*; D008544:Melanocytes; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase; D020928:Mitogen-Activated Protein Kinases; D046988:Proteasome Endopeptidase Complex