title: Suppression of melanin synthesis by the phenolic constituents of sappanwood (Caesalpinia sappan).
abstract: Sappanwood (Caesalpinia sappan Linn.) is used as an herbal medicine. It is sometimes used to treat skin damage or as a facial cleanser. In the present study, the methanol (MeOH) extract of sappanwood was found to inhibit melanin synthesis in cultured human melanoma HMV-II cells stimulated with forskolin, and six active compounds (1-5 and 7) were isolated from the extract along with a non-active compound (6). Compounds 2-7 were identified as sappanchalcone (2), 3'-deoxy-4-O-methylsappanol (3), brazilein, (4), brazilin (5), sappanol (6), and 4-O-methylsappanol (7). Compound 1 was a new compound, and its structure was determined to be (6aS,11bR)-7,11b-dihydro-6H-indeno[2,1-c]chromene-3,6a,10,11-tetrol by spectroscopic analyses. Among the six active compounds, brazilin (5) (EC50: 3.0 ± 0.5 µM) and 4-O-methylsappanol (7) (EC50: 4.6 ± 0.7 µM) strongly suppressed melanin synthesis in HMV-II cells. Bioactive compounds showed moderate cytotoxicities against HMV-II cells with IC50 values of 83.1 ± 4.0 µM (for 2), 72.0 µM ± 2.4 (for 3), 33.8 ± 1.1 µM (for 4), 18.4 ± 0.8 µM (for 5), and 20.2 ± 0.8 (for 7), respectively. Brazilin (5) selectively suppressed the expression of mRNAs for tyrosinase-related protein (TYRP) 2 and tyrosinase but did not influence the expression of TYRP1. These results suggest that brazilin (5) is a new class of melanin inhibitor and that sappanwood could be used as a cosmetic material.
authors.affiliation: Pharmacognosy and Chemistry of Natural Products, School of Pharmacy and Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mitani
authors.forename: Fumihide
authors.initials: F
authors.lastname: Takano
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kawabata
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: Allam
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ota
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yahagi
authors.forename: Chikai
authors.initials: C
authors.lastname: Sakurada
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiya
authors.forename: Tomihisa
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000032:analysis / Q000494:pharmacology*; D029911:Caesalpinia / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007192:Indenes / Q000032:analysis / Q000494:pharmacology*; D008543:Melanins / Q000032:analysis / Q000096:biosynthesis*; D008545:Melanoma / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D007192:Indenes; D008543:Melanins; D010636:Phenols; D010936:Plant Extracts; C050295:brazilein