title: New Whitening Constituents from Taiwan-Native Pyracantha koidzumii: Structures and Tyrosinase Inhibitory Analysis in Human Epidermal Melanocytes.
abstract: Nontoxic natural products useful in skin care cosmetics are of considerable interest. Tyrosinase is a rate-limiting enzyme for which its inhibitor is useful in developing whitening cosmetics. Pyracantha koidzumii (Hayata) Rehder is an endemic species in Taiwan that exhibits tyrosinase-inhibitory activity. To find new active natural compounds from P. koidzumii, we performed bioguided isolation and studied the related activity in human epidermal melanocytes. In total, 13 compounds were identified from P. koidzumii in the present study, including two new compounds, 3,6-dihydroxy-2,4-dimethoxy-dibenzofuran (9) and 3,4-dihydroxy-5-methoxybiphenyl-2'-O-β-d-glucopyranoside (13), as well as 11 known compounds. The new compound 13 exhibited maximum potency in inhibiting cellular tyrosinase activity, the protein expression of cellular tyrosinase and tyrosinase-related protein-2, as well as the mRNA expression of Paired box 3 and microphthalmia-associated transcription factor in a concentration-dependent manner. In the enzyme kinetic assay, the new compound 13 acted as an uncompetitive mixed-type inhibitor against the substrate l-3,4-dihydroxyphenylalanine and had a Km value against this substrate of 0.262 mM, as calculated using the Lineweaver-Burk plots. Taken together, our findings show compound 13 exhibits tyrosinase inhibition in human melanocytes and compound 13 may be a potential candidate for use in cosmetics.
authors.affiliation: Department of Internal Medicine, Heping Branch, Taipei City Hospital, Taipei 100, Taiwan. lrd678@gmail.com.
authors.forename: Rong-Dih
authors.initials: RD
authors.lastname: Lin
authors.affiliation: Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. mcchen1250@tmu.edu.tw.|Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. mcchen1250@tmu.edu.tw.
authors.forename: Mei-Chuan
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. yann0119@hotmail.com.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. acnnkiey1026@gmail.com.|Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. acnnkiey1026@gmail.com.
authors.forename: Yi-Tzu
authors.initials: YT
authors.lastname: Lin
authors.affiliation: National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, Taiwan. mklu@nricm.edu.tw.
authors.forename: Mei-Kuang
authors.initials: MK
authors.lastname: Lu
authors.affiliation: Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. hsu0320@tmu.edu.tw.
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. lmh@tmu.edu.tw.|Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan. lmh@tmu.edu.tw.|Center for Reproductive Medicine &amp; Sciences, Taipei Medical University Hospital, Taipei 110, Taiwan. lmh@tmu.edu.tw.
authors.forename: Mei-Hsien
authors.initials: MH
authors.lastname: Lee
mesh_terms: D057886:Bleaching Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects; D006801:Humans; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D031991:Pyracantha / Q000737:chemistry*; D013624:Taiwan
chemical_list: D057886:Bleaching Agents; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D014442:Monophenol Monooxygenase
keywords: 3,4-dihydroxy-5-methoxybiphenyl-2′-O-β-d-glucopyranoside; Paired box 3; Pyracantha koidzumii; human epidermal melanocytes; microphthalmia-associated transcription factor; tyrosinase; tyrosinase-related proteins