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The purpose of this study was to determine the inhibitory action of protocatechuic aldehyde (PCA) on tyrosinase activity. PCA is one of the compounds found in the root of Salvia miltiorrhiza. Our study documented that PCA has a potent inhibitory effect on tyrosinase, which catalyzes the rate-limiting step of melanin biosynthesis. Although melanin biosynthesis has an essential function normally in human skin for defense against ultraviolet light of the sun, its abnormal activity as seen in pigmentation disorder could lead to serious medical problems. Our data showed that PCA, with concentrations ranging from 1×10^-5M to 8×10^-5M, exhibited dose-dependent inhibition of the enzyme activity with 50% of inhibition at 19.92×10^-6M. A further kinetic analysis on PCA inactivation of tyrosinase activity revealed a competitive inhibition of the enzyme at the L-tyrosine binding site. The findings of our present study merit further research on the applicability of PCA as a potential agent for treatment of pigmentation disorder.

Ligusticum sinensis Oliv. (LSO) is an herbal drug commonly used as a topical treatment of epidermal hyperdepigmentation in Chinese medicine. However, the mechanism underlying the depigmentation by LSO is still unclear. The purpose of this study was to investigate the effects of LSO on the process of melanogenesis and its possible underlying mechanism. Suppressed DOPA oxidase activity of mushroom tyrosinase was first noted when incubated with aqueous extracts of LSO, demonstrating the direct inhibitory effect of LSO on mushroom tyrosinase. Further experiments were carried out in murine B16/F10 melanoma cells and the effects of LSO extract on melanin formation, tyrosinase activity and tyrosinase gene expression were tested. Under conditions without affecting the viability of murine B16/F10 melanoma cells, LSO extract significantly reduced the cellular melanin content in a dose-dependent manner. The DOPA oxidase activity of tyrosinase in B16/F10 cells was dose-dependently inhibited by LSO treatment, possibly mediated by the suppressed tyrosinase mRNA expression in LSO-treated B16/F10 cells. In conclusion, the inhibitory effect of LSO on melanogenesis is likely associated with decreased DOPA oxidase activity of tyrosinase that is most likely the result of the down-regulation of tyrosinase mRNA expression.

Down-regulation of melanin synthesis and\or melanin transfer are\is required for recovery of pigmentary disorders. It is known that direct inhibitors of tyrosinase, the key enzyme in melanin synthesis, such as hydroquinone with a phenol structure, suppress melanin synthesis. We screened some herbal monomers using human melanocytes and found that paeonol, a major phenolic component of Moutan Cortex, down-regulated melanin synthesis. The melanin synthesis and tyrosinase activity were inhibited by paeonol in a dose-dependent manner. The expression levels of tyrosinase mRNA and protein were also reduced by paeonol. We further studied the inhibitory effects of paeonol on melanin transfer in co-culture of melanocytes and keratinocytes. More than 50% of inhibition of melanin transfer was observed at concentration of 200 μM of paeonol and the increased melanin transfer induced by SLIGRL, the PAR-2 activating peptide, was also reduced by paeonol. However, paeonol did not influence the expression level of PAR-2 mRNA in co-culture cells. These results indicate that the depigmenting effect of paeonol might be due to its down-regulation of melanogenesis and melanin transfer.

For cosmetic reasons, the demand for effective and safe skin-whitening agents is high. Since the key enzyme in the melanin synthetic pathway is tyrosinase, many depigmenting agents in the treatment of hyperpigmentation act as tyrosinase inhibitors. In this study, we have investigated the hypo-pigmentary mechanism of royal jelly in a mouse melanocyte cell line, B16F1. Treatment of B16F1 cells with royal jelly markedly inhibited melanin biosynthesis in a dose-dependent manner. Decreased melanin content occurred through the decrease of tyrosinase activity. The mRNA levels of tyrosinase were also reduced by royal jelly. These results suggest that royal jelly reduces melanin synthesis by down-regulation of tyrosinase mRNA transcription and serves as a new candidate in the design of new skin-whitening or therapeutic agents.

Three cationic zinc phthalocyanines (ZnPcs), tetrakis-(3-methylpyridyloxy)-, tetrakis-(3-hexyl-pyridyloxy)-, and tetrakis-(3-dodecylpyridyloxy)phthalocyaninezinc (ZnPcMe, ZnPcHe and ZnPcDo) have been studied as advanced fluorescent contrast agents for pigmented melanoma tumor. UV-vis spectroscopic properties of the monomers were investigated. Their photophysical behavior as a substantial part of dye-induced fluorescence was evaluated. The selective accumulation and labeling capacity towards B16F0 pigmented melanoma tumor were determined. Melanin containing cells were isolated and incubated with ZnPcs at several time intervals (1, 1.5 and 6 h) following the kinetics of cellular uptake. The highest accumulation was found for ZnPcHe. A lower uptake was detected for the more lipophilic ZnPcDo and more hydrophilic ZnPcMe. The fluorescence diagnostic potential of ZnPcs towards pigmented melanoma by using an argon-dye laser detection set-up was demonstrated.

Background: Skin cutaneous melanoma (SKCM) is a highly aggressive form of skin cancer characterized by rapid metastasis and poor prognosis. PRAME (Preferentially Expressed Antigen in Melanoma) is an oncogene overexpressed in various cancers, including melanoma, and is implicated in tumorigenesis and immune evasion. Understanding the spatial expression patterns of PRAME in SKCM can provide insights into the disease mechanism and therapeutic targets. Aim of the Study: This study aims to spatially resolve the transcriptomic profile of PRAME in SKCM and evaluate the therapeutic potential of selected dermato-oncology agents through molecular docking. Methods: Spatial transcriptomics was performed on SKCM tissue samples from 30 patients to map PRAME expression. Differential expression analysis and spatial clustering were conducted. Molecular docking using HDock assessed the binding affinities of PRAME with dermato-oncology agents: vemurafenib, dioxybenzone and octocrylene, as well as their conjugates (O-D: octocrylene-dioxybenzone, O-V: octocrylene-vemurafenib and D-V: dioxybenzone-vemurafenib). Chemsketch facilitated the creation of conjugates, and Pymol was used for visualization. Results: PRAME was significantly upregulated in SKCM tissues, with a mean expression level of 8.5 TPM compared to 1.2 TPM in normal tissues ($p$ < 0.001). HDock analysis revealed that dioxybenzone had a binding energy of –106.08 kcal/mol, octocrylene –107.04 kcal/mol, and vemurafenib –114.15 kcal/mol. The conjugates showed improved binding affinities: O-D had –142.93 kcal/mol, O-V had –152.69 kcal/mol and D-V had –184.53 kcal/mol, with D-V showing the most substantial binding affinity. Conclusion: Spatial transcriptomic profiling highlights PRAME as a key biomarker in SKCM. The molecular docking results indicate that D-V conjugates (dioxybenzone-vemurafenib) possess the highest binding affinity (–184.53 kcal/mol), suggesting a promising therapeutic potential for SKCM treatment. These findings support further investigation into D-V conjugates as targeted treatments for melanoma. Future Prospects: Future research should focus on in vivo validation of the identified therapeutic agents and exploring the role of PRAME in SKCM pathogenesis. Additionally, combining spatial transcriptomics with other omics data could enhance our understanding of the tumor microenvironment and lead to novel therapeutic approaches.