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

Abstract

The development of antimelanogenic agents is important for the prevention of serious aesthetic problems such as melasma, freckles, age spots and chloasma. The aim of this study was to investigate the antimelanogenic effect of sesamol, an active lignan isolated from Sesamum indicum, in melan‐a cells. Sesamol strongly inhibited melanin biosynthesis and the activity of intracellular tyrosinase by decreasing cyclic adenosine monophosphate (cAMP) accumulation. Sesamol significantly decreased the expression of melanogenesis‐related genes, such as tyrosinase, tyrosinase‐related protein‐1,2 (TRP‐1,2), microphthalmia‐associated transcription factor (MITF) and melanocortin 1 receptor (MC1R). In addition, sesamol also induces phosphorylation of p38 mitogen‐activated protein kinase (p38 MAPK) and c‐Jun N‐terminal kinase (JNK). Moreover, sesamol dose‐dependently decreased zebrafish pigment formation, tyrosinase activity and expression of melanogenesis‐related genes. These findings indicate that sesamol inhibited melanin biosynthesis by down‐regulating tyrosinase activity and melanin production via regulation of gene expression of melanogenesis‐related proteins through modulation of MITF activity, which promoted phosphorylation of p38 and JNK in melan‐a cells. Together, these results suggest that sesamol strongly inhibits melanin biosynthesis, and therefore, sesamol represents a new skin‐whitening agent for use in cosmetics.

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

“…The formazan produced was then dissolved in 100% dimethyl sulfoxide (DMSO), and of cell or well absorbances were measured at 570 nm using a microplate reader (Victor3, PerkinElmer, Waltham, MA, USA). Percentage viabilities were calculated versus non-treated controls2.…”

“…Tyrosinase activity was determined spectrophotometrically as previously described, with minor modification2. Briefly, mixtures of 0.1 M phosphate buffer (pH 6.5) (100 μl), 1 mM L-tyrosine (50 μl), mushroom tyrosinase (EC 1.14.18.1; 200 units ml −1 in phosphate buffer, pH 6.5) with or without jineol at different concentrations were prepared in a 96-well microplate (SPL, Pocheon, Korea).…”

“…Despite its advantages, abnormal melanin production is responsible for several skin diseases, such as, albinism, leukoplakia, melasma, freckles, moles, and lentigo1, and thus, the modulation of melanogenesis is viewed as an important strategy for treating abnormal skin pigmentation. Melanogenesis involves a series of enzymes, such as, tyrosinase, TYRP-1, and TYRP-2, and their transcription factors, microphthalamia-associated transcription factor (MITF), and diverse signal transduction pathways2. Tyrosinase (a copper containing enzyme) plays a key role in the synthesis of melanin, as it catalyzes the two rate-limiting reactions of melanogenesis, namely the hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine (DOPA) (monophenolase) and the oxidation of DOPA to dopaquinone (diphenolase)3.…”

“…Furthermore, mitogen-activated protein kinase (MAPK) signaling via extracellular-signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK, leads to MITF ubiquitination and degradation and plays a pivotal role in suppressing melanin production2.…”

Inhibitory effects of N,N,N-trimethyl phytosphingosine-iodide on melanogenesis via ERK activation-mediated MITF degradation

“…28,29) We showed that L-TMP treatment induces the phosphorylation of not only ERK, but also p38 MAPK. In our study, the abrogating effect of PD98059 on L-TMP-induced suppression of MITF and tyrosinase activity was weak.…”