title: Manassantin B inhibits melanosome transport in melanocytes by disrupting the melanophilin-myosin Va interaction.
abstract: Human skin hyperpigmentation disorders occur when the synthesis and/or distribution of melanin increases. The distribution of melanin in the skin is achieved by melanosome transport and transfer. The transport of melanosomes, the organelles where melanin is made, in a melanocyte precedes the transfer of the melanosomes to a keratinocyte. Therefore, hyperpigmentation can be regulated by decreasing melanosome transport. In this study, we found that an extract of Saururus chinensis Baill (ESCB) and one of its components, manassantin B, inhibited melanosome transport in Melan-a melanocytes and normal human melanocytes (NHMs). Manassantin B disturbed melanosome transport by disrupting the interaction between melanophilin and myosin Va. Manassantin B is neither a direct nor an indirect inhibitor of tyrosinase. The total melanin content was not reduced when melanosome transport was inhibited in a Melan-a melanocyte monoculture by manassantin B. Manassantin B decreased melanin content only when Melan-a melanocytes were co-cultured with SP-1 keratinocytes or stimulated by α-MSH. Therefore, we propose that specific inhibitors of melanosome transport, such as manassantin B, are potential candidate or lead compounds for the development of agents to treat undesirable hyperpigmentation of the skin.
authors.affiliation: R&D Center, AmorePacific Corporation, Giheung-gu, Yongin-si, Gyeonggi-do, Korea.
authors.forename: Huikyoung
authors.initials: H
authors.lastname: Chang
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Choi
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Joo
authors.forename: Daegun
authors.initials: D
authors.lastname: Kim
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D058965:MART-1 Antigen / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020460:Melanosomes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000378:metabolism; D024701:Myosin Type V / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D032134:Saururaceae / Q000737:chemistry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005663:Furans; D058965:MART-1 Antigen; D008543:Melanins; D010936:Plant Extracts; C482885:manassantin B; D014442:Monophenol Monooxygenase; D024701:Myosin Type V