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.

Plants are affected by changes in light and adaptation mechanisms can affect secondary metabolite synthesis. In this study, the physiological response and regulation of the coumarin biosynthetic pathway of Angelica dahurica to different light intensities (natural light (CK), shade rate 50% (L1), shade rate 70% (L2), and shade rate 90% (L3)) were examined. The chlorophyll content, level of the enzymes of the antioxidant system, extent of lipid peroxidation, and concentrations of the osmoregulatory solute levels were determined in potted plants. Root transcriptome under different light intensities was sequenced using high-throughput technology, and differentially expressed genes (DEGs) related to coumarin biosynthesis were analyzed by quantitative real-time PCR (qRT-PCR). With increasing shade, Chl a, Chl b, Chl a + b, and Chl a/b content increased, while the Chl a/b ratio decreased. The antioxidant enzyme system activity and extent of membrane lipid peroxidation increased. The soluble protein (SP) and proline (Pro) content decreased with the reduction in the light intensity, and soluble sugar (SS) content was found to be highest at 50% shade. The RNA-seq analysis showed that 9388 genes were differentially expressed in the L3 group (7561 were upregulated and 1827 were downregulated). In both the L1 and L2 groups, DEGs were significantly enriched in “Ribosome biosynthesis”; meanwhile, in the L3 group, the DEGs were significantly enriched in “Amino and ribonucleotide sugar metabolism” in KEGG metabolic pathway analysis. Additionally, 4CL (TRINITY_DN40230_c0_g2) and COMT (TRINITY_DN21272_c0_g1) of the phenylpropanoid metabolic pathway were significantly downregulated in the L3 group. In conclusion, A. dahurica grew best under 50% shade and the secondary-metabolite coumarin biosynthetic pathway was inhibited by 90% shade, affecting the yield and quality of medicinal compounds.

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Yufeng Huang

Papers

Inhibitory mechanisms of glabridin on tyrosinase.

Effects of Light Intensity on Physiological Characteristics and Expression of Genes in Coumarin Biosynthetic Pathway of Angelica dahurica