title: Tyrosol and its analogues inhibit alpha-melanocyte-stimulating hormone induced melanogenesis.
abstract: Melanin is responsible for skin color and plays a major role in defending against harmful external factors such as ultraviolet (UV) irradiation. Tyrosinase is responsible for the critical steps of melanogenesis, including the rate-limiting step of tyrosine hydroxylation. The mechanisms of action of skin hypopigmenting agents are thought to be based on the ability of a given agent to inhibit the activity of tyrosinase and, hence, down regulate melanin synthesis. Tyrosol and its glycoside, salidroside, are active components of Rhodiola rosea, and in our preliminary study we found that Rhodiola rosea extract inhibited melanogenesis. In this study, we examined the effects of tyrosol and its analogues on melanin synthesis. We found that treatment of B16F0 cells to tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), 2-hydroxyphenylacetic acid (7), or salidroside (11) resulted in a reduction in melanin content and inhibition of tyrosinase activity as well as its expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5) and 2-hydroxyphenylacetic acid (7) suppressed MC1R expression. Tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) inhibited α-MSH induced TRP-1 expression, but salidroside (11) did not. All the compounds did not affect MITF and TRP-2 expression. Furthermore, we found that the cell viability of tyrosol (1), 4-hydroxyphenylacetic acid (5), 3-hydroxyphenylacetic acid (6), and 2-hydroxyphenylacetic acid (7) at concentrations below 4 mM and salidroside (11) at concentrations below 0.5 mM were higher than 90%. The compounds exhibited metal-coordinating interactions with copper ion in molecular docking with tyrosinase. Our results suggest that tyrosol, 4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, 2-hydroxyphenylacetic acid, and salidroside are potential hypopigmenting agents.
authors.affiliation: Department of Cosmeceutics, China Medical University, Taichung 404, Taiwan. hmchiang@mail.cmu.edu.tw.
authors.forename: Kuo-Ching
authors.initials: KC
authors.lastname: Wen
authors.forename: Chih-Shiang
authors.initials: CS
authors.lastname: Chang
authors.forename: Yin-Chih
authors.initials: YC
authors.lastname: Chien
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Wang
authors.forename: Wan-Chen
authors.initials: WC
authors.lastname: Wu
authors.forename: Chin-Sheng
authors.initials: CS
authors.lastname: Wu
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Chiang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D051379:Mice; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry*; D029771:Rhodiola / Q000737:chemistry / Q000378:metabolism; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D008543:Melanins; D010936:Plant Extracts; C011867:4-hydroxyphenylethanol; D000521:alpha-MSH; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; D010626:Phenylethyl Alcohol