Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date. This review has focused on the tyrosinase inhibitors discovered from all sources and biochemically characterised in the last four decades.

https://northumbria-test.eprints-hosting.org/id/document/268389

A comprehensive review on tyrosinase inhibitors.

Melanogenesis is the process for the production of melanin, which is the primary cause of human skin pigmentation. Skin-whitening agents are commercially available for those who wish to have a lighter skin complexions. To date, although numerous natural compounds have been proposed to alleviate hyperpigmentation, insufficient attention has been focused on potential natural skin-whitening agents and their mechanism of action from the perspective of compound classification. In the present article, the synthetic process of melanogenesis and associated core signaling pathways are summarized. An overview of the list of natural skin-lightening agents, along with their compound classifications, is also presented, where their efficacy based on their respective mechanisms of action on melanogenesis is discussed.

/pdf/natural-skin-whitening-compounds-for-the-treatment-of-33i5hgpqh5.pdf

Natural skin-whitening compounds for the treatment of melanogenesis (Review).

Synthesis, antioxidant and anti-tyrosinase activity of 1,2,4-triazole hydrazones as antibrowning agents.

Licorice is extensively applied in food as well as herbal medicine across the world, possessing a substantial share in the global market. It has made great progress in chemical and pharmacological research in recent years. Currently, Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., and Glycyrrhiza glabra L. were officially used as Gan-Cao according to the Chinese Pharmacopoeia. Accumulating evidence demonstrated three varieties of licorice have their own special compounds except for two quality markers set by Pharmacopoeia, providing great possibility for better understanding their characteristics, evaluating quality of each species and studying biosynthesis mechanisms of species-specific compounds. As a special "guide drug" in clinic, licorice plays an important role in Chinese herbal formulas. The interaction between licorice with other ingredients and their metabolism in vivo should also be taken into consideration. In addition, draft genome annotation, and success of the final step of glycyrrhizin biosynthesis have paved the way for biosynthesis of other active constituents in licorice, a promising beginning of solving source shortage. Accordingly, we comprehensively explored the nearly 400 chemical compounds found in the three varieties of licorice so far, systematically excavated various pharmacological activities, including metabolism via CYP450 system in vivo, and introduced the complete biosynthesis pathway of glycyrrhizin in licorice. The review will facilitate the further research toward this herbal medicine.

A Comprehensive Review for Phytochemical, Pharmacological, and Biosynthesis Studies on Glycyrrhiza spp.

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.

https://www.mdpi.com/1420-3049/23/1/106/pdf

Synergistic Promotion on Tyrosinase Inhibition by Antioxidants

Inhibitory mechanisms of glabridin on tyrosinase.

Phloretin as both a substrate and inhibitor of tyrosinase: Inhibitory activity and mechanism

The related structure-activity relationships of cinnamic acid and its derivates have not been studied in details yet. Herein, antityrosinase and antioxidant activities of 18 compounds were evaluated. The results demonstrated that the substituents on the phenyl ring of cinnamic acid led to the enhancement of the inhibition on monophenolase and the weakening of the inhibition on diphenolase. Among these tested compounds, 9 was first discovered as a tyrosinase inhibitor in a reversible competitive manner with IC50 value of 68.6 ± 4.2 µm. Docking results demonstrated 9 located into the catalytic center of tyrosinase. Antioxidant assay indicated that only 1 hydroxyl group on the phenyl ring was not enough to possess the radical scavenging activity, and the number of hydroxyl groups may be more important. This study will be helpful in the development of new cinnamic acid derivates as tyrosinase inhibitors and antioxidants with higher efficacy.

Structure-activity relationships of antityrosinase and antioxidant activities of cinnamic acid and its derivatives.

Tyrosinase is a key metalloenzyme for the biosynthesis of melanin that plays a critical role in the prevention of skin damage caused by ultraviolet (UV) radiation. However, the overproduction of melanin may cause a variety of skin diseases. Due to the toxicity and inefficiency of existing tyrosinase inhibitors, it is urgent to identify safe and potent alternatives from natural sources. Theaflavin, a single-component extracted from black tea, has been found to possess a variety of pharmacological activities. Herein, the inhibition kinetics of theaflavin on tyrosinase and inhibitory mechanism were determined using spectroscopy, molecular docking, and zebrafish model. The results showed that theaflavin inhibited the diphenolase activity of tyrosinase in a reversible mixed type manner with IC50 of 229.75 μmol/L and hindered the synthesis of melanin in zebrafish. This may be due to the formation of eight hydrogen bonds and hydrophobic effects between theaflavin and tyrosinase according to the results of molecular docking. To study the possible effects on the prevention of free radical-mediated skin cancer and photoaging caused by UV radiation, the antioxidation and UV filter properties of theaflavin were further verified. This study demonstrates that theaflavin is a potential multifunctional compound that can be used in cosmetic and medicinal products.

Evaluation of antityrosinase activity and mechanism, antioxidation, and UV filter properties of theaflavin.

The invention provides a slow-release microneedle as well as a preparation method thereof. The preparation method comprises the following steps: preparing a soluble microneedle, preparing a coating layer, and drying and molding the product. According to the technical scheme, an ultrasonic atomization microneedle coating mode is adopted, and a uniform coating layer is formed on the surface of the soluble microneedle by using a water-insoluble high polymer material; the thickness of the coating layer can be adjusted through the number of times of ultrasonic atomization and the ultrasonic atomization time, and medicine in the soluble microneedle can gradually permeate to the outside through holes in the coating layer. Due to the obstruction of the coating layer, the release speed of the medicine becomes slow, so that the slow release effect of the medicine in the soluble microneedle is realized. Meanwhile, in the storing, transporting and using process, the coating layer can isolate the medicine from moisture in the air, the protection effect is achieved, and therefore the mechanical strength of the microneedle and the stability of the medicine are guaranteed.

Jianmin Chen

Papers

Inhibitory mechanisms of glabridin on tyrosinase.

Phloretin as both a substrate and inhibitor of tyrosinase: Inhibitory activity and mechanism

Structure-activity relationships of antityrosinase and antioxidant activities of cinnamic acid and its derivatives.

Evaluation of antityrosinase activity and mechanism, antioxidation, and UV filter properties of theaflavin.

Slow-release microneedle as well as preparation method and equipment thereof