title: Discovery of highly potent tyrosinase inhibitor, T1, with significant anti-melanogenesis ability by zebrafish in vivo assay and computational molecular modeling.
abstract: Tyrosinase is involved in melanin biosynthesis and the abnormal accumulation of melanin pigments leading to hyperpigmentation disorders that can be treated with depigmenting agents. A natural product T1, bis(4-hydroxybenzyl)sulfide, isolated from the Chinese herbal plant, Gastrodia elata, is a strong competitive inhibitor against mushroom tyrosinase (IC50 = 0.53 μM, Ki = 58 ± 6 nM), outperforms than kojic acid. The cell viability and melanin quantification assay demonstrate that 50 μM of T1 apparently attenuates 20% melanin content of human normal melanocytes without significant cell toxicity. Moreover, the zebrafish in vivo assay reveals that T1 effectively reduces melanogenesis with no adverse side effects. The acute oral toxicity study evidently confirms that T1 molecule is free of discernable cytotoxicity in mice. Furthermore, the molecular modeling demonstrates that the sulfur atom of T1 coordinating with the copper ions in the active site of tyrosinase is essential for mushroom tyrosinase inhibition and the ability of diminishing the human melanin synthesis. These results evident that T1 isolated from Gastrodia elata is a promising candidate in developing pharmacological and cosmetic agents of great potency in skin-whitening.
authors.affiliation: 1] The School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan [2] Department of Chinese Medicine, E-Da hospital, Kaohsiung, Taiwan.
authors.forename: Wang-Chuan
authors.initials: WC
authors.lastname: Chen
authors.affiliation: 1] National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan [2] Institute of Biotechnology, National Changhua University of Education, Changhua, Taiwan.
authors.forename: Tien-Sheng
authors.initials: TS
authors.lastname: Tseng
authors.affiliation: Institute of Biotechnology, National Changhua University of Education, Changhua, Taiwan.
authors.forename: Nai-Wan
authors.initials: NW
authors.lastname: Hsiao
authors.affiliation: National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
authors.forename: Yun-Lian
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.affiliation: 1] The School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan [2] Department of Chinese Medicine, E-Da hospital, Kaohsiung, Taiwan.
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: 1] Antibody and Hybridoma Core Facility, Taipei Medical University, Taipei, Taiwan [2] The Center of Translational Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lee
authors.affiliation: 1] National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan [2] Institute of Biotechnology, National Changhua University of Education, Changhua, Taiwan.
authors.forename: Hui-Hsiung
authors.initials: HH
authors.lastname: Lin
authors.affiliation: National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
authors.forename: Keng-Chang
authors.initials: KC
authors.lastname: Tsai
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D020128:Inhibitory Concentration 50; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D023382:Toxicity Tests, Acute; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008543:Melanins; D014442:Monophenol Monooxygenase