title: Hyperpigmentation mechanism of methyl 3,5-di-caffeoylquinate through activation of p38 and MITF induction of tyrosinase.
abstract: Methyl 3,5-di-caffeoylquinate (3,5-diCQM) has been used for the treatment of various diseases in oriental medicine, but its effect on melanogenesis has not been reported yet. In this study, the molecular mechanism of 3,5-diCQM-induced melanogenesis was investigated. It was found that 3,5-diCQM induced synthesis of melanin pigments in murine B16F10 melanoma cells in a concentration-dependent manner. Treatment of cells with 3,5-diCQM for 48 h increased extracellular and intracellular melanin production and tyrosinase activity. The expressions of tyrosinase, tyrosinase-related protein 1 (TRP1), and TRP2 were up-regulated in a dose-dependent manner 48 h after 3,5-diCQM treatment. Western blot analysis showed that 3,5-diCQM increased the phosphorylation of p38 mitogen-activated protein kinase and cAMP responsive element binding as well as the expression of microphthalmia-associated transcription factor. In addition, 3,5-diCQM-stimulated cAMP production, and 3,5-diCQM-induced tyrosinase activity and melanin synthesis were attenuated by H89, a protein kinase A inhibitor. These results suggested that 3,5-diCQM-mediated activation of the p38 pathway may represent a novel approach for an effective therapy for vitiligo and hair graying.
authors.affiliation: Research Institute for Biological Functions, Chubu University, Kasugai, Aichi 487-8501, Japan.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Research Institute for Biological Functions, Chubu University, Kasugai, Aichi 487-8501, Japan Department of Research and Development, Erina Co., Inc., Minato-ku, Tokyo 105-0021, Japan.
authors.forename: Je-Tae
authors.initials: JT
authors.lastname: Woo
authors.affiliation: KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, Republic of Korea.
authors.forename: Ik-Soo
authors.initials: IS
authors.lastname: Lee
authors.affiliation: Research Institute for Biological Functions, Chubu University, Kasugai, Aichi 487-8501, Japan bycha@isc.chubu.ac.jp.
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Cha
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002726:Chlorogenic Acid / Q000031:analogs & derivatives; D004789:Enzyme Activation; D004790:Enzyme Induction; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000502:physiology*; D014442:Monophenol Monooxygenase / Q000096:biosynthesis*; D010859:Pigmentation Disorders / Q000139:chemically induced*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D002109:Caffeic Acids; D051739:Microphthalmia-Associated Transcription Factor; D011801:Quinic Acid; D002726:Chlorogenic Acid; C478100:3,4-di-O-caffeoylquinic acid; D014442:Monophenol Monooxygenase; D048051:p38 Mitogen-Activated Protein Kinases
keywords: melanogenesis; methyl 3,5-di-caffeoylquinate (3,5-diCQM); microphthalmia-associated transcription factor (MITF); p38 mitogen-activated protein kinase (p38 MAPK); tyrosinase