Inhibitory mechanisms of glabridin on tyrosinase.
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin in the human body. Overproduction of melanin could lead to a variety of skin disorders. Glabridin, an isoflavan, isolated from the root of Glycyrrhiza glabra Linn, has exhibited several pharmacological activities, including excellent inhibitory effects on tyrosinase. In this paper, the inhibitory kinetics of glabridin on tyrosinase and their binding mechanisms were determined using spectroscopic, zebrafish model and molecular docking techniques. The results indicate that glabridin reversibly inhibits tyrosinase in a noncompetitive manner through a multiphase kinetic process with the IC50 of 0.43μmol/L. It has been shown that glabridin had a strong ability to quench the intrinsic fluorescence of tyrosinase mainly through a static quenching procedure, suggesting a stable glabridin-tyrosinase complex may be generated. The results of molecular docking suggest that glabridin did not directly bind to the active site of tyrosinase. Moreover, according to the results of zebrafish model system, glabridin shows no effects on melanin synthesis in zebrafish but presents toxicity to zebrafish embryo. The possible inhibitory mechanisms, which will help to design and search for tyrosinase inhibitors especially for glabridin analogues, were proposed.
College of Pharmaceutical and Medical technology, Putian University, Fujian, China. Electronic address: chenjianmin1985@sina.com.
Jianmin
J
Chen
College of Pharmaceutical and Medical technology, Putian University, Fujian, China.
Xiaojing
X
Yu
College of Pharmaceutical and Medical technology, Putian University, Fujian, China.
Yufeng
Y
Huang
D000364:Agaricus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D008543:Melanins / Q000378:metabolism; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D015027:Zebrafish
D004791:Enzyme Inhibitors; D007529:Isoflavones; D008543:Melanins; D010636:Phenols; D014442:Monophenol Monooxygenase; C107601:glabridin
Fluorescence quenching; Glabridin; Inhibitory mechanisms; Molecular docking; Tyrosinase; Zebrafish model