Constituents from the Formosan apple reduce tyrosinase activity in human epidermal melanocytes.
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.
Lin
Yi-Pei
YP
Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, 250 Wu Hsing Street, Taipei 110, Taiwan.
Hsu
Feng-Lin
FL
Chen
Chien-Shu
CS
Chern
Ji-Wang
JW
Lee
Mei-Hsien
MH
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
C521865:3-hydroxyphloretin; D000975:Antioxidants; D002396:Catechols; D016166:Free Radical Scavengers; D008543:Melanins; D010936:Plant Extracts; D014442:Monophenol Monooxygenase; C034221:catechol; D010693:Phloretin