Hyperpigmentation mechanism of methyl 3,5-di-caffeoylquinate through activation of p38 and MITF induction of tyrosinase

Abstract

Methyl 3,5-di-caffeoylquinate (3,5-diCQM) has been used for the treatment of various diseases in oriental medicine, but its effect on melanogenesis has not been reported yet. In this study, the molecular mechanism of 3,5-diCQM-induced melanogenesis was investigated. It was found that 3,5-diCQM induced synthesis of melanin pigments in murine B16F10 melanoma cells in a concentrationdependent manner. Treatment of cells with 3,5-diCQM for 48 h increased extracellular and intracellular melanin production and tyrosinase activity. The expressions of tyrosinase, tyrosinase-related protein 1 (TRP1), and TRP2 were up-regulated in a dose-dependent manner 48 h after 3,5-diCQM treatment. Western blot analysis showed that 3,5-diCQM increased the phosphorylation of p38 mitogen-activated protein kinase and cAMP responsive element binding as well as the expression of microphthalmiaassociated transcription factor. In addition, 3,5-diCQM-stimulated cAMP production, and 3,5-diCQMinduced tyrosinase activity and melanin synthesis were attenuated by H89, a protein kinase A inhibitor. These results suggested that 3,5-diCQM-mediated activation of the p38 pathway may represent a novel approach for an effective therapy for vitiligo and hair graying.

Preparation of novel 1,2,3-triazole furocoumarin derivatives via click chemistry and their anti-vitiligo activity

“…Aer that, all these derivatives were further studied for their stimulating effect on tyrosinase. 37 As shown in Fig. 7, only two compounds (8a, 8o) showed a higher value than 8-MOP.…”

An Isoxazole Chalcone Derivative Enhances Melanogenesis in B16 Melanoma Cells via the Akt/GSK3β/β-Catenin Signaling Pathways

“…B16 cells were seeded in a six-well plate (2 × 10 5 cells/well) and allowed to attach for 24 h. Cultured B16 cells were incubated in the absence or presence of PMPP for 48 h and then washed with ice-cold PBS twice. After the cells were lysed according to a previously described method with a slight modification [ 8 ], each lysate (150 μL) was put in a 96-well microplate and measured spectro-photometrically at 405 nm by a multi-plate reader. The protein concentration of each sample was determined by a BCA Protein Assay Kit (Biomed, Beijing, China).…”

“…TYR is the primary enzyme in melanogenesis that catalyzes two different chemical reactions: the hydroxylation of tyrosine to produce 3,4-dihydroxyphenylalanine (DOPA) and the oxidation of DOPA to DOPA quinone [ 7 ]. TRP-1 oxidizes 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to indole-5,6-quinone-2-carboxylic acid in mice, but not in humans, whereas TRP-2 catalyzes the rearrangement of DOPA chrome to DHICA [ 8 ]. Microphthalmia-associated transcription factor (MITF) is known to be the master regulator of melanocyte differentiation, pigmentation, proliferation, and survival [ 9 ].…”

A novel psoralen derivative-MPFC enhances melanogenesis via activation of p38 MAPK and PKA signaling pathways in B16 cells

“…B16 cells were seeded in a 6-well plate at a density of 2x10 5 cells/well and allowed to attach for 24 h. Then adding test samples to individual wells, cells were incubated for 48 h and washed with PBS. After cells were lysed according to the method previously described (9), lysate was put in a 96-well microplate, and measured spectro-photometrically at 405 nm by a multi-plate reader. Protein concentration of each sample was determined by BCA Protein assay kit (Biomed, Beijing, China).…”