Molecular inhibitory mechanism of dihydromyricetin on mushroom tyrosinase

Abstract

Tyrosinase is the rate-limiting enzyme for controlling the production of melanin in the human body, and overproduction of melanin can lead to a variety of skin disorders. In this paper, the inhibitory kinetics of Dihydromyricetin (DHM) on tyrosinase and their binding mechanism were determined using spectroscopy, molecular docking, antioxidant assays, and chromatography. The spectroscopic results indicate that DHM reversibly inhibits tyrosinase in a mixed-type manner through a multiphase kinetic process with the IC of 849.88 μM. It is shown that DHM has a strong ability to quench the intrinsic fluorescence of tyrosinase mainly through a static quenching procedure, suggesting that a stable DHM-tyrosinase complex is generated. Molecular docking results suggest that the dominant conformation of DHM does not directly bind to the active site of tyrosinase. Moreover, the antioxidant assays demonstrate that DHM has powerful antioxidant and reducing capacity but does not have the ability to reduce dopachrome to L-DOPA. Interestingly, the results of spectroscopy and chromatography indicate that DHM is a substrate of tyrosinase but not a suicide substrate. The possible inhibitory mechanism is proposed, which will be helpful to design and search for tyrosinase inhibitors.

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

“…Remarkably, quercetin acts as a cofactor and does not inhibit monophenolase activity. The common feature of these three avonols [167][168][169][170][171][172] is that they all inhibit diphenolase activity by chelating copper in the enzyme. Furthermore, quercetin glucoside, with an IC 50 value of 1.9 mM, inhibited tyrosinase more effectively than the positive standard, kojic acid.…”

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

“…Low IC50 values against both monophenolase and diphenolase activty of mushroom tyrosinase have been very recently reported for p-coumaric and caffeic acid [66], belonging to the cinammic acid family ( Figure 7). The IC50 values together with structural formulas for other phenolic compounds widely distributed in nature that have been the subject of studies that appeared in the last five years [53,62,63,[67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82] Low IC 50 values against both monophenolase and diphenolase activty of mushroom tyrosinase have been very recently reported for p-coumaric and caffeic acid [66], belonging to the cinammic acid family ( Figure 7). Moving to simple phenols, significant inhibition activity has been described for 4-hydroxybenzyl alcohol (IC50 = 6 μM) [61] and isoeugenol (IC50 = 33.3 μM) [62], which would appear more efficient than resorcinol [55] or rhododendrol [63] themselves.…”

“…Low IC50 values against both monophenolase and diphenolase activty of mushroom tyrosinase have been very recently reported for p-coumaric and caffeic acid [66], belonging to the cinammic acid family (Figure 7). The IC50 values together with structural formulas for other phenolic compounds widely distributed in nature that have been the subject of studies that appeared in the last five years [53,62,63,[67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82] The IC 50 values together with structural formulas for other phenolic compounds widely distributed in nature that have been the subject of studies that appeared in the last five years [53,62,63,[67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82] are also reported in Figures 4-8.…”

The Binding Affinity of Small Molecules with Yam Tyrosinase (Catechol Oxidase): A Biophysical Study

“…The data obtained from these fluorescence studies also supported the competition experiments. A few reports on mushroom tyrosinase have quoted the change in fluorescence before and after the addition of inhibitors such as flavonoids [17], glycolic acid [31], and dihydromyricetin [32]. The conformational change was evaluated by measuring the fluorescence intensity of the mushroom tyrosinase after addition of condensed tannins from Ficus virens showing antityrosinase activity [33].…”