Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K/Akt, MEK/ERK and Wnt/β-Catenin Signaling Pathways in B16F10 Cells

Abstract

Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis signaling pathways. Gallic acid significantly inhibited both melanin synthesis and tyrosinase activity in a dose- and time-dependent manner, and decreased the expression of melanogenesis-related proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and dopachrome tautomerase (Dct). In addition, gallic acid also acts by phosphorylating and activating melanogenesis inhibitory proteins such as Akt and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Using inhibitors against PI3K/Akt (LY294002) or MEK/ERK-specific (PD98059), the hypopigmentation effect was suppressed, and the gallic acid-initiated activation of MEK/ERK and PI3K/Akt was also revoked. Gallic acid also increased GSK3β and p-β-catenin expression but down-regulated p-GSK3β. Moreover, GSK3β-specific inhibitor (SB216763) restored gallic acid-induced melanin reduction. These results suggest that activation of the MEK/ERK, PI3K/Akt, and inhibition of Wnt/β-catenin signaling pathways is involved in the melanogenesis signaling cascade, and that activation by gallic acid reduces melanin synthesis via down-regulation of MITF and its downstream signaling pathway. In conclusion, gallic acid may be a potentially agent for the treatment of certain skin conditions.

Transcriptome profiling of the cancer and adjacent nontumor tissues from cervical squamous cell carcinoma patients by RNA sequencing

“…Cytochrome P450 is considered as a key participant in the progression of lung cancer and a potentially valuable target for anticancer drug [31]. It has been reported that the MEK/ERK, PI3K/Akt, and Wnt/β-catenin pathways were involved in the melanogenesis signaling cascade [32]. The DEGs in these pathways might be involved in the progress of CSCC.…”

Mansonone E from <i>Mansonia gagei</i> Inhibited α-MSH-Induced Melanogenesis in B16 Cells by Inhibiting CREB Expression and Phosphorylation in the PI3K/Akt Pathway

“…Analytical Instrument of Active Component 1 H (400 MHz) and 13 C (100 MHz) NMR spectra were recorded with a JEOL ECX 400 spectrometer with tetramethylsilane as an internal standard. The high-resolution MS were obtained using a LC/MSD TOF-G1969A (Agilent Technologies, Santa Clara, CA, U.S.A.).…”

“…12) Recently, it was reported that melanogenesis is controlled by various intracellular signaling molecules such as cAMP/protein kinase A (PKA), phosphoinositide 3-kinase (PI3K)/Akt, and ras/mitogen-activated protein kinases (MAPK). 13) cAMP/PKA regulates the expression level of MITF, 14) and ras/MAPK enhances transcriptional activity by promoting phosphorylation of MITF. 15) Experiments using inhibitors suggested that the PI3K/Akt pathway is also involved in melanogenesis.…”

A Novel Stilbene-Like Compound That Reduces Melanin through Inhibiting Melanocyte Differentiation and Proliferation without Inhibiting Tyrosinase

“…Only several skin-lightening compounds have demonstrated the ability to inhibit tyrosinase in addition to activating or inhibiting intracellular signal cascades leading to the transcriptional inhibition of melanin synthesis genes, such as haginin A (Kim et al [10]), gallic acid (Su et al [12]), and hydroquinone (Inoue et al [25]). These studies focused on the MAPK and Akt signaling pathways.…”