title: Constituents from the Formosan apple reduce tyrosinase activity in human epidermal melanocytes.
abstract: Tyrosinase is a copper-containing monooxygenase that catalyzes melanin synthesis in skin melanocytes. Herein, 13 compounds from the Formosan apple (Malus doumeri var. formosana), an indigenous Taiwanese plant, were isolated and identified. The active constituents were identified as 3-hydroxyphloretin (7) and catechol (9); they exhibited potent hydroxyl radical-scavenging (IC(50) values, 0.6 and 1.1 microM) and cellular tyrosinase-reducing activities (IC(50) values, 32 and 22 microM) in human epidermal melanocytes. In addition, we evaluated the level of several tyrosinase-related proteins by Western blot analysis. In contrast to 3-hydroxyphloretin (7), which showed no effect on the level of these proteins, catechol (9) reduced their activity and the expression of the respective genes, as determined by quantitative real-time PCR. In a kinetic analysis of mushroom tyrosinase, 3-hydroxyphloretin (7) was a competitive inhibitor. These two constituents exhibited metal-coordinating interactions with copper ions in a virtual model of molecular docking with human tyrosinase. Thus, 3-hydroxyphloretin (7) and catechol (9) were the most active constituents from the Formosan apple; they exhibited anti-oxidant and tyrosinase reducing activities, suggesting their possible use as cosmetic agents.
authors: Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, 250 Wu Hsing Street, Taipei 110, Taiwan.
authors: Yi-Pei
authors: YP
authors: Lin
authors: Feng-Lin
authors: FL
authors: Hsu
authors: Chien-Shu
authors: CS
authors: Chen
authors: Ji-Wang
authors: JW
authors: Chern
authors: Mei-Hsien
authors: MH
authors: Lee
mesh_terms: D000363:Agaricales / Q000201:enzymology; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015153:Blotting, Western; D002396:Catechols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D003198:Computer Simulation; D016166:Free Radical Scavengers / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D027845:Malus / Q000737:chemistry*; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects*; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010693:Phloretin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry
chemical_list: C521865:3-hydroxyphloretin; D000975:Antioxidants; D002396:Catechols; D016166:Free Radical Scavengers; D008543:Melanins; D010936:Plant Extracts; D014442:Monophenol Monooxygenase; C034221:catechol; D010693:Phloretin