[6]-Shogaol Inhibitsα-MSH-Induced Melanogenesis through the Acceleration of ERK and PI3K/Akt-Mediated MITF Degradation

Abstract

[6]-Shogaol is the main biologically active component of ginger. Previous reports showed that [6]-shogaol has several pharmacological characteristics, such as antioxidative, anti-inflammatory, antimicrobial, and anticarcinogenic properties. However, the effects of [6]-shogaol on melanogenesis remain to be elucidated. The study aimed to evaluate the potential skin whitening mechanisms of [6]-shogaol. The effects of [6]-shogaol on cell viability, melanin content, tyrosinase activity, and the expression of the tyrosinase and microphthalmia-associated transcription factor (MITF) were measured. The results revealed that [6]-shogaol effectively suppresses tyrosinase activity and the amount of melanin and that those effects are more pronounced than those of arbutin. It was also found that [6]-shogaol decreased the protein expression levels of tyrosinase-related protein 1 (TRP-1) and microphthalmia-associated transcriptional factor (MITF). In addition, the MITF mRNA levels were also effectively decreased in the presence of 20 μM [6]-shogaol. The degradation of MITF protein was inhibited by the MEK 1-inhibitor (U0126) or phosphatidylinositol-3-kinase inhibitor (PI3K inhibitor) (LY294002). Further immunofluorescence staining assay implied the involvement of the proteasome in the downregulation of MITF by [6]-shogaol. Our confocal assay results also confirmed that [6]-shogaol inhibited α-melanocyte stimulating hormone- (α-MSH-) induced melanogenesis through the acceleration of extracellular responsive kinase (ERK) and phosphatidylinositol-3-kinase- (PI3K/Akt-) mediated MITF degradation.

Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study

“…It was suggested that a decrease in the protein expression levels of TRP‐1 and MITF by bioactive compound known as [6]‐shogaol (C 17 H 24 O 3 ) and Gomisin N (C 23 H 28 O 6 ) was due to the degradation of MITF protein via acceleration of ERK and phosphatidylinositol‐3‐kinase (PI3K/Akt) pathway . It was also suggested that partially purified Nardostachys chinensis and 1‐O‐methyl‐fructofuranose (C 7 H 14 O 6 ) of Schisandra chinensis markedly reduced MITF, TRP1, TRP2, and TYR protein expressions via reduction of intracellular cAMP levels, and activation of MAPK/ERK and (PI3K)/Akt expression …”

“…Cells have been subjected to stimulants to mimic the actual condition of hyperpigmentation. Various stimulants such as radicals, UVB, α‐MSH, and SCF have been reported where the optimal conditions such as dose concentration, duration, and intensity are varied depending on experimental requirement . For instance, UVB at ~10‐30 mJ UVB, α‐MSH at ~10‐100 nmol/L, lipopolysaccharide (LPS) at 1 μg/mL, and SCF at ~100‐200 ng/mL were used in experiments .…”

“…In contrast, the melanin content was analyzed using in situ melanin assay where the cells were dissolved in 1 mol/L NaOH and at high temperature, and the absorbance was read at 450 or 405 nm . Instead, Soluene‐350 was also used to solubilize melanin in cell for melanin quantification .…”

Melanogenesis‐Inhibitory and Antioxidant Activities of Phenolics from Periploca forrestii

“…Then, MITF directly binds to the promoter regions of melanin production genes which were the most important transcription factor involved in regulation of TYR gene expression . Tyrosinase plays an important role in regulating melanin production by the hydroxylation of tyrosine into dihydroxyphenylalanine (DOPA) followed by further oxidation of DOPA into DOPA quinone, finally resulting in the abnormal accumulation of melanin pigments . For these reasons, melanogenesis‐inhibitors could suppress the expressions of MITF and tyrosinase reasulting in decreasing melanin production.…”

Anti-oxidant Activities of Phytol on Keratinocytes

“…이러한 생강의 효능을 나타내는 주 요 성분은 gingerols, shogaols, paradols 등이고, 이 중 신선한 생 강에 가장 많이 함유되어 있는 gingerols의 가수분해 산물이 바로 shogaols이다 (Bak et al, 2012;Huang et al, 2014) NFΚB reporter NIH3T3 stable cell line (2×10 ⁵ cells/well) was seeded on 60 mm culture dish and then incubated for 24 h. The cells were pre-treated with various concentrations of 6-shogaol for 6 h. Then, the cells were washed by PBS and irradiated by 10 J/cm² UVA. After further incubation for 24 h, inhibition of NFΚB promoter activity by 6-shogaol was determined by the NFΚB promoter luciferase assay.…”