S-(−)-10,11-Dihydroxyfarnesoic Acid Methyl Ester Inhibits Melanin Synthesis in Murine Melanocyte Cells

Abstract

The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasmas, freckles, age spots, and chloasmas. In the course of screening for melanin synthesis inhibitors, we found that the culture broth from an insect morphopathogenic fungus, Beauveria bassiana CS1029, exhibits potent antimelanogenic activity. We isolated and purified an active metabolite and identified it as S-(−)-10,11-dihydroxyfarnesoic acid methyl ester (dhFAME), an insect juvenile hormone. To address whether dhFAME inhibits melanin synthesis, we first measured the size of the melanin biosynthesis inhibition zone caused by dhFAME. dhFAME also showed inhibitory activity against mushroom tyrosinase in Melan-a cells. Intracellular, dose-dependent tyrosinase inhibition activity was also confirmed by zymography. In addition, we showed that dhFAME strongly inhibits melanin synthesis in Melan-a cells. Furthermore, we compared levels of TYR, TRP-1, TRP-2, MITF, and MC1R mRNA expression by reverse-transcription polymerase chain reaction and showed that treatment of Melan-a cells with 35 μM dhFAME led to an 11-fold decrease in TYR expression, a 6-fold decrease in TRP-2 expression, and a 5-fold decrease in MITF expression. Together, these results indicate that dhFAME is a potent inhibitor of melanin synthesis that can potentially be used for cosmetic biomaterial(s).

Inhibition of melanogenesis by jineol from Scolopendra subspinipes mutilans via MAP-Kinase mediated MITF downregulation and the proteasomal degradation of tyrosinase

“…Medium was then replaced with fresh media containing different concentrations of jineol and cultured for a further 72 h. Cells were then washed twice with PBS, lysed with 1 N NaOH, transferred to a 96-well plate, and melanin contents were measured at 405 nm using a microplate reader (VICTOR3, Perkin Elmer). Arbutin was used as the positive control41. Inhibition of melanogenesis (%) was calculated using the following equation:…”

Sesamol decreases melanin biosynthesis in melanocyte cells and zebrafish: Possible involvement of MITF via the intracellular cAMP and p38/JNK signalling pathways

“…Intracellular Tyr activity and zymography were performed as described previously 31. Briefly, the test compound was added to melan‐a cells (1 × 10 5 cells/ml), and the culture cells were harvested with RIPA cell lysis buffer (Elpis Biotech., Taejon, Korea) supplemented with a protease inhibitor.…”

“…cDNA was amplified using a PCR Thermal Cycler Dice TP600 (Takara Bio Inc., Otsu, Shiga, Japan). PCR products were visualized by ethidium bromide staining after electrophoresis 31. The mRNA levels in zebrafish were evaluated as follows: 1 and 2 days after fertilization, embryos (50 per well) were transferred to a 6‐well plate with 5 ml of test solution.…”

Cycloalliin Inhibits Melanin Biosynthesis in B16 Mouse Melanoma Cells

“…Although 100 μM of S-(-)-10,11-dihydroxyfarnesoic acid methyl ester (dhFAME) significantly inhibits the mRNA levels of tyrosinase, TRP1, TRP2, and MITF in murine melanocyte cells, only MITF mRNA expression was reduced when 50 μM of dhFAME was used, and the levels of the rest of the proteins remained unchanged (Baek et al, 2014). Therefore, the inhibitors reducing MITF mRNA expression seem to trigger varied changes in the mRNA expression of other proteins.…”