In vitro and in vivo evidence of tyrosinase inhibitory activity of a synthesized (Z)‐5‐(3‐hydroxy‐4‐methoxybenzylidene)‐2‐thioxothiazolidin‐4‐one (5‐HMT)

Tyrosinase is a key enzyme that catalyses the initial rate‐limiting steps of melanin synthesis. Due to its critical role in melanogenesis, various attempts were made to find potent tyrosinase inhibitors although many were not safe and effective in vivo. We evaluated tyrosinase inhibitory activity of six compounds. Among them, (Z)‐5‐(3‐hydroxy‐4‐methoxybenzylidene)‐2‐thioxothiazolidin‐4‐one (5‐HMT) had the greatest inhibitory effect and potency as the IC₅₀ value of 5‐HMT was lower than that of kojic acid, widely‐known tyrosinase inhibitor. Based on in silico docking simulation, 5‐HMT had a greater binding affinity than kojic acid with a different binding conformation in the tyrosinase catalytic site. Furthermore, its skin depigmentation effect was confirmed in vivo as 5‐HMT topical treatment significantly reduced UVB‐induced melanogenesis in HRM2 hairless mice. In conclusion, our study demonstrated that 5‐HMT has a greater binding affinity and inhibitory effect on tyrosinase and may be a potential candidate for a therapeutic agent for preventing melanogenesis.     

Assessment of gene expression levels of proopiomelanocortin (POMC) and melanocortin‐1 receptor (MC1R) in vitiligo

Proopiomelanocortin (POMC) and melanocortin 1 receptor (MC1R) are regulators of melanogenesis and pigmentation. Our objective was to estimate their levels, searching for a possible role of the melanocortin system in vitiligo. This study included 40 vitiligo patients and 40 controls. Skin biopsies were taken from lesional and non‐lesional skin of patients and from the non‐sun exposed skin of controls to detect the expression of POMC and MC1R using quantitative real‐time polymerase chain reaction. Both factors were significantly lower in lesional than non‐lesional skin and controls, while they were significantly higher in non‐lesional skin than in controls. There was a statistically significant positive correlation between lesional levels of POMC and MC1R, as well as between non‐lesional levels of POMC and MC1R in the patients. On the other hand, we found a statistically significant negative correlation between the lesional and non‐lesional levels of POMC, as well as between the lesional and non‐lesional levels of MC1R in the patients. As a conclusion, the melanocortin system could play a role in the pathogenesis of vitiligo or could be affected as the end result of the disease.     

Inhibitory effects of 16-hydroxy-9-oxo-10E,12E,14E-octadecatrienoic acid (Corchorifatty acid B) isolated from Melissa officinalis Linné on melanogenesis

16-hydroxy-9-oxo-10E,12E,14E-octadecatrienoic acid, also known as Corchorifatty acid B (CFAB), is isolated from the ethanol extracts of the aerial parts of Melissa officinalis Linné (Labiatae) and exhibits inhibitory effects on cellular pigmentation in both human melanocytes and mouse melanoma B16 cells. CFAB specifically decreases cellular melanin by most likely inducing rapid degradation of tyrosinase in B16 cells. Interestingly, unlike other reagents that promote degradation of tyrosinase in proteasomes or lysosomes, neither proteasomal nor lysosomal inhibitors can halt CFAB-induced tyrosinase degradation. Only brefeldin A, which specifically inhibits protein transport from the endoplasmic reticulum to the Golgi complex, can effectively impede CFAB-induced tyrosinase decrease. These results suggest that CFAB-induced tyrosinase decrease occurs in post-Golgi compartments but not in proteasomal or lysosomal compartments. Taken together, CFAB is a unique reagent that primarily accelerates tyrosinase decrease by a mechanism that differs from those considered for other hypopigmentation reagents currently reported.