title: Chemical constituents derived from Artocarpus xanthocarpus as inhibitors of melanin biosynthesis.
abstract: Twenty-four compounds, including the previously unknown artoxanthocarpuone A, artoxanthocarpuone B, hydroxylakoochin A, methoxylakoochin A, epoxylakoochin A, and artoxanthol, were isolated and characterized spectroscopically. Among them, artoxanthol is stilbene oligomer presumably constructed in a 5,11,12-triphenyl hexahydrochrysene scaffold by a Diels-Alder type of reaction, for which a biosynthetic pathway is proposed. Artoxanthol, alboctalol, steppogenin, norartocarpetin, resveratrol, oxyresveratrol, and chlorophorin potently inhibited mushroom tyrosinase activity with IC50 values from 0.9 to 5.7 μM that were all far stronger than the positive controls. Artoxanthocarpuone A, artoxanthocarpuone B, methoxylakoochin A, lakoochin A, cudraflavone C, artonin A, resveratrol, and chlorophorin reduced tyrosinase activity and inhibited α-melanocyte-stimulating hormone-induced melanin production in B16F10 melanoma cells without affecting cell proliferation. Collectively, the results suggest that the constituents of Artocarpus xanthocarpus have potential to be used as depigmentation agents.
authors.affiliation: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Jin
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Cha-Chi
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Tajen University, Pingtung County 907, Taiwan.
authors.forename: Tzy-Ming
authors.initials: TM
authors.lastname: Lu
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Jih-Heng
authors.initials: JH
authors.lastname: Li
authors.affiliation: School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Ih-Sheng
authors.initials: IS
authors.lastname: Chen
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Research Center for Natural Products and Drug Development, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address: hhko@kmu.edu.tw.
authors.forename: Horng-Huey
authors.initials: HH
authors.lastname: Ko
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D031622:Artocarpus / Q000737:chemistry*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008543:Melanins; D013267:Stilbenes; D014442:Monophenol Monooxygenase
keywords: Artocarpus xanthocarpus; Chinese herb; Hexahydrochrysene; Melanin; Moraceae; Oligomer of stilbene; Tyrosinase