Neobavaisoflavone Inhibits Melanogenesis through the Regulation of Akt/GSK-3β and MEK/ERK Pathways in B16F10 Cells and a Reconstructed Human 3D Skin Model

Previous studies have confirmed the anti-melanogenic effect of the aerial part of Pueraria lobata, however, due to its inherent color, P. lobata has limited commercial use. In this study, an extract (GALM-DC) of the aerial part of P. lobata having improved color by the use of activated carbon was obtained. Furthermore, the active compound neobavaisoflavone (NBI) was identified from GALM-DC. The effect of NBI on melanogenesis, tyrosinase activity, α-glucosidase activity, and mechanism of action in melanocytes was investigated. Tyrosinase activity, melanin contents and the expression of melanin-related genes and proteins were determined in B16F10 cells. NBI reduced melanin synthesis and tyrosinase activity. Furthermore, NBI treatment reduced the mRNA and protein expression levels of MITF, TRP-1, and tyrosinase. NBI also works by phosphorylating and activating proteins that inhibit melanogenesis, such as GSK3β and ERK. Specific inhibitors of Akt/GSK-3β (LY294002) and MEK/ERK (PD98059) signaling prevented the inhibition of melanogenesis by NBI. NBI inhibited melanin production through the regulation of MEK/ERK and Akt/GSK-3β signaling pathways in α-MSH-stimulated B16F10 cells. NBI suppresses tyrosinase activity and melanogenesis through inhibition of α-glucosidase activity. Besides, NBI significantly reduced melanogenesis in a reconstructed human 3D skin model. In conclusion, these results suggest that NBI has potential as a skin-whitening agent for hyperpigmentation.

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Inhibitory Effects of Cycloheterophyllin on Melanin Synthesis

Molecules ◽

10.3390/molecules26092526 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2526

Author(s):

Joong-Hyun Shim

Keyword(s):

Functional Materials ◽

Tyrosinase Activity ◽

Melanin Synthesis ◽

Activity Assay ◽

Inhibitory Effects ◽

Melanin Production ◽

Messenger Ribonucleic Acid ◽

B16f10 Cells ◽

Cell Line Cell ◽

Tyrosinase Related Protein

This study was performed to clarify the inhibitory effects of cycloheterophyllin on melanin synthesis. In order to elucidate the inhibitory effects of cycloheterophyllin on the B16F10 cell line, cell viability, messenger ribonucleic acid (mRNA) expressions, tyrosinase activity assay, and melanin production assay were measured. The effects of cycloheterophyllin on tyrosinase-related protein 1 (TYRP1)/TYRP2/tyrosinase (TYR)/microphthalmia-associated transcription factor (MITF) mRNA expressions and melanin content were determined. Quantitative real-time RT-PCR showed that cycloheterophyllin decreased the mRNA expression level of TYRP1/TYRP2/TYR/MITF genes and melanin production contents than α-MSH-treated B16F10 cells. The tyrosinase activity assay revealed that cycloheterophyllin decreased the melanin production in the B16F10 cells. These data show that cycloheterophyllin increases the whitening effects in the B16F10 cells; thus, cycloheterophyllin is a potent ingredient for skin whitening. Thus, further research on the mechanism of action of cycloheterophyllin for the development of functional materials should be investigated.

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Basic Red 51, a permitted semi-permanent hair dye, is cytotoxic to human skin cells: Studies in monolayer and 3D skin model using human keratinocytes (HaCaT)

Toxicology Letters ◽

10.1016/j.toxlet.2014.03.007 ◽

2014 ◽

Vol 227 (2) ◽

pp. 139-149 ◽

Cited By ~ 22

Author(s):

Thalita B. Zanoni ◽

Manoela Tiago ◽

Fernanda Faião-Flores ◽

Silvia B. de Moraes Barros ◽

Aalt Bast ◽

...

Keyword(s):

Human Skin ◽

Human Keratinocytes ◽

Skin Model ◽

Hair Dye ◽

Skin Cells ◽

Human Skin Cells ◽

3D Skin

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Generation of a plant polypeptide library and screening with a 3D skin model

Biochemical Society Transactions ◽

10.1042/bst029a111 ◽

2001 ◽

Vol 29 (5) ◽

pp. A111-A111

Author(s):

I. Horan ◽

A.M. O'Brien ◽

P.T. Tomkins

Keyword(s):

Skin Model ◽

3D Skin

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Mixture toxicity of methylisothiazolinone and propylene glycol on the skin irritation tested by human 3D skin model, EpiDerm™

Toxicology Letters ◽

10.1016/j.toxlet.2016.06.1696 ◽

2016 ◽

Vol 258 ◽

pp. S189-S190

Author(s):

K. Park ◽

J. Park ◽

H. Lee ◽

J. Lee

Keyword(s):

Propylene Glycol ◽

Skin Irritation ◽

Mixture Toxicity ◽

Skin Model ◽

3D Skin

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Anti-Melanogenic Effects of Hydroxyectoine via MITF Inhibition by JNK, p38, and AKT Pathways in B16F10 Melanoma Cells

Natural Product Communications ◽

10.1177/1934578x19858523 ◽

2019 ◽

Vol 14 (6) ◽

pp. 1934578X1985852 ◽

Cited By ~ 1

Author(s):

You C. Chung ◽

Min-Jin Kim ◽

Eun Y. Kang ◽

Yun B. Kim ◽

Bong S. Kim ◽

...

Keyword(s):

Skin Color ◽

Inhibitory Effect ◽

Tyrosinase Activity ◽

Dependent Manner ◽

Related Protein ◽

B16f10 Melanoma ◽

Melanin Production ◽

B16f10 Cells ◽

Dose Dependent ◽

Tyrosinase Related Protein

Melanin plays a role in determining human skin color of a person, and a large amount of melanin makes the skin color look darkened. The proper amount of melanin formation protects our skin from UV radiation, but excessive melanin production causes hyperpigmentation and leads to freckles, melasma, and lentigo. In this study, we investigated the inhibitory effect of hydroxyectoine on melanogenesis and its mechanism in B16F10 cells. Melanin content and cellular tyrosinase activity were determined. The expression of microphthalmia-associated transcription factor (MITF), and the activities of tyrosinase and other melanogenesis-related enzymes, such as tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2, were also examined. Hydroxyectoine treatment significantly inhibited melanin production and intracellular tyrosinase activity in a dose-dependent manner. Western blot analysis showed that hydroxyectoine also reduced the expressions of tyrosinase and TRP-1. In addition, hydroxyectoine significantly reduced the expression of MITF, a major regulator of melanin production, and inhibited the phosphorylation of p38, c-Jun N-terminal kinase, and activated the protein kinase B. The results demonstrated that hydroxyectoine inhibits the expression of MITF through the inhibition or activation of melanin-related signaling pathways and downregulates melanogenesis by inhibiting melanogenic enzyme expression and tyrosinase activity. Hydroxyectoine has potential value in functional cosmetics applications, such as whitening.

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Sapindus mukorossi Seed Oil Changes Tyrosinase Activity of α-MSH-Induced B16F10 Cells Via the Antimelanogenesic Effect of Eicosenoic Acid

Natural Product Communications ◽

10.1177/1934578x20972295 ◽

2020 ◽

Vol 15 (11) ◽

pp. 1934578X2097229

Author(s):

Yu-Hsiang Lin ◽

Chia-Jen Nien ◽

Lih-Geeng Chen ◽

Sheng-Yang Lee ◽

Wei-Jen Chang ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Seed Oil ◽

Unsaturated Fatty Acids ◽

Eicosenoic Acid ◽

Tyrosinase Activity ◽

Control Group ◽

Melanin Formation ◽

Model Free ◽

B16f10 Cells

Melanogenesis is a complex process that can lead to pigmentation defects. Various chemical skin-lightening products have been developed to treat pigmentation disorders. However, these chemical products can cause harmful adverse effects. Therefore, the development of safer, natural bleaching ingredients is a trend for sustainability. It has been reported that unsaturated fatty acids exhibit significant antimelanogenic effects. Sapindus mukorossi seed oils contain abundant unsaturated fatty acids; however, these have not yet been investigated for beneficial effects on skin tone evenness. In this study, we tested the possibility of using S. mukorossi oil for the treatment of hyperpigmentation in an in vitro model. Free fatty acid compositions and β-sitosterol were determined by gas chromatography-mass spectrometry and high-pressure liquid chromatography, respectively. The effect of S. mukorossi oil on melanoma B16F10 cell viability was detected using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide assay. The inhibitive effects of fatty acids and β-sitosterol in S. mukorossi oil on α-melanocyte-stimulating hormone (MSH)-induced melanogenesis was evaluated by detecting melanin formation and tyrosinase activity. Our results showed that S. mukorossi oil produced no significant cytotoxicity in B16F10 cells at various concentrations compared with the control group. The enhancement of melanin formation induced by α-MSH was reduced by S. mukorossi oil. We also found that the primary fatty acid contributing to the antimelanogenesis effect was eicosenoic acid. These results suggest that S. mukorossi seed oil can effectively inhibit melanogenesis and has the potential for future development as a de-hyperpigmentation product within a waste utilization context.

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Nrf2 Overexpression for the Protective Effect of Skin-Derived Precursors against UV-Induced Damage: Evidence from a Three-Dimensional Skin Model

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/7021428 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Dehai Xian ◽

Xia Xiong ◽

Jixiang Xu ◽

Li Xian ◽

Qirong Lei ◽

...

Keyword(s):

Three Dimensional ◽

Cell Swelling ◽

Histological Structure ◽

Related Factor ◽

Type I ◽

Apoptotic Cells ◽

Ros Scavenging ◽

Skin Model ◽

Protective Genes ◽

3D Skin

Background. Skin photodamage is associated with ultraviolet- (UV-) induced reactive oxygen species (ROS) overproduction and nuclear factor erythroid 2-related factor 2 (Nrf2) inactivation. In our previous study, skin-derived precursors (SKPs) were shown to ameliorate a UV-induced damage in mice, probably through Nrf2 activation and ROS scavenging. Objective. To clarify the mechanism underlying the photoprotective effect of SKPs against UV-induced damage in a three-dimensional (3D) skin model. Methods. The Nrf2 gene in SKPs was modified using lentiviral infection, and 3D skin models were reconstructed with keratinocytes and fibroblasts on the basis of type I collagen. Subsequently, these models were divided into the following six groups: normal, model, overexpressed, control, silenced, and negative control groups. Prior to irradiation, respective SKPs were injected into the last four groups. Next, all groups except the normal group were exposed to UVA+UVB. Lastly, the pathological and molecular-biological techniques were employed to determine the parameters. Additionally, LY294002, a PI3K inhibitor, was used to investigate the roles of PI3K/Akt and Nrf2/hemeoxygenase-1 (HO-1) in SKP photoprotection. Results. Normal 3D skin models appeared as milky-white analogs with a clear, well-arranged histological structure. After the skin was exposed to irradiation, it exhibited cell swelling and a disorganized structure and developed nuclear condensation with numerous apoptotic cells. The expressions of cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins remarkably decreased, which were accompanied by increased oxidative stress and decreased antioxidants (P<0.05). However, these phenomena were reversed by nrf2-overexpressing SKPs. The 3D skin in the overexpressed group showed mild swelling, neatly arranged cells, and few apoptotic cells. Cellular protective genes and Nrf2/HO-1/PI3K/Akt proteins were highly expressed, and the oxidative biomarkers were remarkably ameliorated (P<0.05). Nevertheless, the expression of these proteins decreased after LY294002 pretreatment regardless of SKP treatment or not. Meanwhile, there were increases in both UV-induced apoptotic cells and ROS level accompanied with SOD and GPX decrease in the presence of LY294002. Conclusions. Evidence from the 3D skin model demonstrates that the protection of SKPs against UV-mediated damage is primarily via the PI3K/Akt-mediated activation of the Nrf2/HO-1 pathway, indicating that SKPs may be a promising candidate for the treatment of photodermatoses.

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