Synergistic Promotion on Tyrosinase Inhibition by Antioxidants

Abstract

When exposed to ultraviolet radiation, the human skin produces profuse reactive oxygen species (ROS), which in turn activate a variety of biological responses. Mounting ROS levels activate tyrosinase by mobilizing α-melanocyte-stimulating hormone in the epidermis and finally stimulates the melanocytes to produce melanin. Meanwhile, the Keap1-Nrf2/ARE pathway, which removes ROS, is activated at increased ROS levels, and antioxidant compounds facilitates the dissociation of Nrf2. In this study, we explored the possible suppressing effects of antioxidant compounds and tyrosine inhibitors on melanin formation and the promotory effects of these compounds on ROS scavenging. The antioxidant activity of glabridin (GLA), resveratrol (RES), oxyresveratrol (OXYR), and phenylethylresorcinol (PR) were investigated via the stable free radical 2,2-diphenyl-1-picrylhydrazyl method. The inhibitory effects of the four compounds and their mixtures on tyrosinase were evaluated. l-Tyrosine or 3-(3,4-dihydroxyphenyl)-l-alanine (l-DOPA) was used as a substrate. The results showed that all mixtures did not exhibit synergistic effects with the l-tyrosine as a substrate, suggesting that l-tyrosine is not suitable as a substrate. However, the mixtures of “GLA:RES,” “GLA:OXYR,” “OXYR:RES,” and “PR:RES” demonstrated synergistic effects (CI < 0.9, p < 0.05), whereas “GLA:RES” and “PR:OXYR” indicated an additive effect (0.9 ditive1, p < 0.05). Furthermore, we used a molecular docking strategy to study the interactions of the four compounds with tyrosinase and l-DOPA. The molecular docking result is consistent with that of the experiment. Finally, we selected RES + OXYR and used PIG1 cells to verify whether OXYR synergistically promotes RES activity on tyrosinase. The two agents had a synergistic inhibitory effect on tyrosinase activity. These results provided a novel synergistic strategy for antioxidants and tyrosinase inhibitors, and this strategy is useful in skin injury treatment.

Polyphenol Profile and Biological Activity Comparisons of Different Parts of Astragalus macrocephalus subsp. finitimus from Turkey

“…In fact, the greatest positive correlation occurred among tyrosinase and antioxidant properties. The existence of an interesting relationship between antioxidant defense systems and melanogenesis is well documented [ 76 ]. In fact, by reacting with toxic ROS result in the restriction of radical chain propagation, eventually preventing the skin from damage.…”

“…In fact, by reacting with toxic ROS result in the restriction of radical chain propagation, eventually preventing the skin from damage. Besides, the cytoprotective antioxidants can be increased by antioxidant molecules thanks to the nuclear accumulation of Nrf2, which is a main transcription factor for the oxidative stress regulation in human skin tissues such as melanocyte, keratinocytes, and dermal fibroblasts [ 76 ].…”

Achillea millefolium L. and Achillea biebersteinii Afan. Hydroglycolic Extracts–Bioactive Ingredients for Cosmetic Use

“…The inhibition of the monophenolase activity of mushroom tyrosinase by Achillea HG extracts was performed based on the protocol described by Wang and co-workers [ 47 ] with some modifications. 80 μL of phosphate buffer (100 mM, pH = 6.8) was mixed with 20 μL of diluted sample and 20 μL mushroom tyrosinase (500 U) and pre-incubated for 10 min at room temperature.…”

A comprehensive review on tyrosinase inhibitors

“…Synergistic strategy for tyrosinase inhibitors is a useful strategy for the improvement of their inhibitory activities. Based on the findings, the mixtures of glabridin:resveratrol, glabridin:oxyresveratrol, resveratrol:oxyresveratrol, phenylethylresorcinol:resveratrol 441 , oxyresveratrol:dioscin 442 , aloesin:arbutin 443 , 4-methyl catechol: catechol 444 , 3-(2,4-dihydroxyphenyl)propionic acid:l-ascorbic acid 445 , dihydromyricetin:vitamin D3 37 , linderanolide B combined with arbutin, 1-phenyl-2-thiourea or kojic acid 446 , have shown synergistic effect on tyrosinase. These studies may provide a scientific strategy for screening effective tyrosinase inhibitors.…”