Natural Citrus flavanone 5-demethylnobiletin stimulates melanogenesis through the activation of cAMP/CREB pathway in B16F10 cells

Wang, Hui-Miao; Li, Qu; Ng, Jerome P. L.; Zeng, Wu; Yu, Lu; Song, Lin Lin; Wong, Vincent Kam Wai; Cheng, Xia; Law, Betty Yuen‐Kwan

doi:10.1016/j.phymed.2022.153941

Cited by 21 publications

(14 citation statements)

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“…TRP-2 acts as a dopachrome tautomerase, converting dopachrome to 5,6-dihydroxyl indole-2-carboxylic acid (DHICA), while TRP-1 oxidizes and polymerizes DHICA to form carboxylated indole quinone. The production of these three enzymes is transcriptionally regulated by microphthalmia-associated transcription factor (MITF), which is the master regulator of the differentiation, pigmentation, proliferation, and survival of melanocytes [ 4 ]. In addition, pharmacological research has verified that MTF is regulated through various signal pathways, such as the cyclic adenosine monophosphate (cAMP)-mediated pathway, the mitogen-activated protein kinase (MAPK), the phosphatidylinositol 3 kinase (PI3K)/AKT pathway, and the Wnt signaling pathway at a transcriptional or post-translational level.…”

Section: Introductionmentioning

confidence: 99%

A 7-Hydroxy 4-Methylcoumarin Enhances Melanogenesis in B16-F10 Melanoma Cells

Kim

Hyun

2023

Molecules

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The objectives of this study were to investigate the melanogenetic potentials of the naturally occurring 7-hydroxy coumarin derivatives 7-hydroxy 5,6-dimethoxycoumarin (7H-5,6DM), 7-hydroxy 6,8-dimethoxycoumarin (7H-6,8DM), 7-hydroxy 6-methoxycoumarin (7H-6M), and 7-hydroxy 4-methylcoumarin (7H-4M) in the melanogenic cells model for murine B16F10 melanoma cells. The initial results indicated that melanin production and intracellular tyrosinase activity were significantly stimulated by 7H-4M but not by 7H-5,6DM, 7H-6,8DM, or 7H-6M. Therefore, our present study further investigated the melanogenic effects of 7H-4M in B16-F10 cells, as well as its mechanisms of action. In a concentration-dependent manner, 7H-4M increased intracellular tyrosinase activity, leading to the accumulation of melanin without affecting the viability of B16-F10 cells. Our study further investigated the effects of 7H-4M on melanogenesis, including its ability to promote tyrosinase activity, increase melanin content, and activate molecular signaling pathways. The results indicate that 7H-4M effectively stimulated tyrosinase activity and significantly increased the expression of melanin synthesis-associated proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and TRP2. Based on our findings, we can conclude that 7H-4M has the ability to activate the melanogenesis process through the upregulation of cAMP-dependent protein kinase (PKA) and the cAMP response element-binding protein (CREB). Additionally, our study showed that 7H-4M induced melanogenic effects by downregulating the extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/glycogen synthesis kinase-3β (GSK-3β) cascades, while upregulating the JNK and p38 signaling pathways. Finally, the potential of using 7H-4M in topical applications was tested through primary human skin irritation tests. During these tests, no adverse reactions were induced by 7H-4M. In summary, our results indicate that 7H-4M regulates melanogenesis through various signaling pathways such as GSK3β/β-catenin, AKT, PKA/CREB, and MAPK. These findings suggest that 7H-4M has the potential to prevent the development of pigmentation diseases.

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Section: Introductionmentioning

confidence: 99%

A 7-Hydroxy 4-Methylcoumarin Enhances Melanogenesis in B16-F10 Melanoma Cells

Kim

Hyun

2023

Molecules

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“…B16F10 cells were used to assay the antimelanogenic effects of the samples [ 20 ]. The cytotoxicity of the sample in B16F10 cells was measured with the MTT assay.…”

Section: Methodsmentioning

confidence: 99%

“…The relative gene expression levels were analyzed as 2 −ΔΔCq values for each sample relative to β-Actin . All the specific primers are shown in Table 1 (Bioneer Co.; Daejeon, Korea) [ 20 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Improved Antioxidative, Anti-Inflammatory, and Antimelanogenic Effects of Fermented Hydroponic Ginseng with Bacillus Strains

Park

Song

Kim³

et al. 2022

Antioxidants

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Compared with traditionally cultured ginseng, hydroponic ginseng (HG) contains more remarkable bioactive compounds, which are known to exert diverse functional effects. This study aimed to enhance the multifunctional effects, including the antioxidative, anti-inflammatory, and antimelanogenic effects, exhibited by fermented HG with Bacillus strains, such as Bacillus subtilis KU43, Bacillus subtilis KU201, Bacillus polyfermenticus SCD, and Bacillus polyfermenticus KU3, at 37 °C for 48 h. After fermentation by B. subtilis KU201, the antioxidant activity, determined using ABTS and FRAP assays, increased from 25.30% to 51.34% and from 132.10% to 236.27%, respectively, accompanied by the enhancement of the phenolic compounds and flavonoids. The inflammation induced in RAW 264.7 cells by lipopolysaccharide (LPS) was ameliorated with fermented HG, which regulated the nitric oxide (NO), prostaglandin E2 (PGE2), and proinflammatory markers (tumor necrosis factor (TNF)-α, and interleukin (IL)-1β and IL-6). The treatment with fermented HG inhibited the melanin accumulation in B16F10 cells induced by α-melanocyte-stimulating hormone (α-MSH) by controlling the concentrations of melanin synthesis and tyrosinase activity. These results indicate that the HG exhibited stronger antioxidative, anti-inflammatory, and antimelanogenic effects after fermentation. Consequently, HG fermented by Bacillus strains can potentially be used as an ingredient in cosmetological and pharmaceutical applications.

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“…[11][12][13] According to the different molecular structures, flavonoids are mainly classified into flavones, flavanones, cate-chins, and anthocyanins. [14][15][16][17][18][19] Among the flavonoids, quercetin (Fig. 1) is the major polyphenolic flavonoid in various fruits and vegetables.…”

Section: Introductionmentioning

confidence: 99%