Understanding the inhibitory mechanism of tea polyphenols against tyrosinase using fluorescence spectroscopy, cyclic voltammetry, oximetry, and molecular simulations

Abstract

Inhibiting the activity of tyrosinase is a very effective and safe way to prevent enzymatic browning in food and to resist pests in agriculture. Tea polyphenols (TPs), regarded as safe and non-toxic food additives, have been reported due to their potential inhibitory capability against tyrosinase, but their ambiguous inhibitory mechanisms have severely limited their application. In the present work, fluorescence spectroscopy, cyclic voltammetry (CV), oximetry and molecular simulation approaches were employed to shed light on the underlying inhibitory mechanisms of TPs with different structures including (+)-catechin, (À)-epicatechin gallate (ECG) and (À)-epigallocatechin gallate (EGCG) against tyrosinase. Fluorescence spectra show that the three TPs are capable of binding tyrosinase with a molar proportion of 1 : 1. The analysis of CV curves and oxygen utilization suggests that these three TPs can be oxidized by tyrosinase, revealing that these three TPs are suicide inhibitors of tyrosinase. Furthermore, ECG and catechin make tyrosinase irreversibly inactivated due to their catechol group (ring B) being catalyzed by tyrosinase through a cresolase-like pathway, while EGCG inhibits the activity of tyrosinase by competing with or delaying the oxidation of substrate. Molecular simulations further confirm that ring B of ECG and catechin makes a significant contribution to tyrosinase inhibitory activities, and has a direct interaction with the coupled binuclear copper ions in the optimal orientation required by the cresolase-like pathway.

Natural and synthetic flavonoid derivatives as new potential tyrosinase inhibitors: a systematic review

“…153 Kaempferol, myricetin, quercetin, isorhamnetin, galangin, morin, and their glycosides are the prevalent naturally occurring avonols, mostly found as O-glycosides. [154][155][156][157][158][159][160] So far, several avonols such as quercetin from Olea europaea, kaempferol from Hypericum laricifolium, and Crocus sativus, quercetin-4 0 -O-beta-D-glucoside from Parornix bifurca, quercetin glucopyranoside and kaempferol glucopyranoside from mulberry leaves, morin and 2,3-cis-dihydromorin, 2,3-transdihydromorin from Chloropsis cochinchinensis, were found to act as tyrosinase inhibitors (Table 12). Moreover, it was reported that three 3-hydroxyavones including kaempferol, galangin, and quercetin inhibit the L-DOPA oxidation process catalyzed by tyrosinase, and apparently, this TI activity arises from their Cu 2+ chelating ability.…”

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

“…A significant melanogenesis inhibition potential has been reported also for galangin (IC 50 = 3.55 µM) [52], isoliquiritigenin (IC 50 = 4.85 µM) [53], kaempferol (IC 50 = 5.5 µM) [54], and dihydromorin (IC 50 = 9.4 µM) [55], belonging to different flavonoid subfamilies, but all characterized by at least one resorcinol moiety. IC50 values in the range 20-150 µM have instead been reported for catechins [56][57][58][59]. Among natural phenolic compounds acting as tyrosinase inhibitors (Supplementary Materials, Table S1), flavonoids are the most representative class.…”

A comprehensive review on tyrosinase inhibitors

“…Additionally, further improvements of in vitro detection methods for rapidly screening tyrosinase inhibitors may be achieved through using virtual screening 30 and construction of quantitative structure–activity relationship (QSAR) models of inhibitors 31 , 32 . Thus, a combination of bioinformatics simulation and biological in vitro analysis will be useful to understand the functional mechanisms of the tested compounds 9 , 21 , 27 , 33–48 . Lately, Gao et al.…”