title: Proanthocyanidins purified from fruit pericarp of Clausena lansium (Lour.) Skeels as efficient tyrosinase inhibitors: structure evaluation, inhibitory activity and molecular mechanism.
abstract: Fruit pericarp of Clausena lansium (Lour.) Skeels, a food waste, was selected as a raw material for proanthocyanidins. The proanthocyanidins' structures were integrally analyzed using three methods: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), high performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS) and13C nuclear magnetic resonance (NMR). The results elucidated that these compounds were composed of prodelphinidin (75%) and procyanidin (25%) with a degree of polymerization (DP) up to the 20-mers. They were proved to be remarkable, reversible and mixed competitive inhibitors of tyrosinase according to results from enzyme experiments. The IC50values were calculated to be 23.6 ± 1.2 and 7.0 ± 0.2 μg mL-1for the monophenolase and diphenolase activities, respectively. In addition, the proanthocyanidins had a good inhibitory effect on cell proliferation, cellular tyrosinase activity and melanin production of B16mouse melanoma cells. Chelation between the hydroxyl group on the B ring of the proanthocyanidins and dicopper irons of the enzyme provided one of the feasible mechanisms for the inhibition on the basis of fluorescence quenching and molecular docking analyses. This research would supply the scientific basis to these compounds application in the pharmaceutical, insecticides, and preservative fields.
authors.affiliation: College of Life Science and Key Laboratory of Poyang Lake Wetland and Watershed Research, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, China. chaiweiming@jxnu.edu.cn zouzhr@163.com and Key Laboratory of Small Functional Organic Molecule, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.
authors.forename: Wei-Ming
authors.identifier: http://orcid.org/0000-0001-9163-8138
authors.initials: WM
authors.lastname: Chai
authors.affiliation: College of Life Science and Key Laboratory of Poyang Lake Wetland and Watershed Research, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, China. chaiweiming@jxnu.edu.cn zouzhr@163.com.
authors.forename: Mei-Zhen
authors.initials: MZ
authors.lastname: Lin
authors.affiliation: Zigong Innovation Center of Zhejiang University, Zigong, Sichuan 643000, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Feng
authors.affiliation: College of Life Science and Key Laboratory of Poyang Lake Wetland and Watershed Research, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, China. chaiweiming@jxnu.edu.cn zouzhr@163.com.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Zou
authors.affiliation: College of Life Science and Key Laboratory of Poyang Lake Wetland and Watershed Research, Ministry of Education, Jiangxi Normal University, Nanchang, Jiangxi 330022, China. chaiweiming@jxnu.edu.cn zouzhr@163.com.
authors.forename: Ying-Xia
authors.initials: YX
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002477:Cells / Q000187:drug effects / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D054700:Clausena / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D044945:Proanthocyanidins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D044945:Proanthocyanidins; D014442:Monophenol Monooxygenase