Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: Role of MAPK and Akt pathways

Ko, Horng‐Huey; Chiang, Yu-Ting; Tsai, Ming-Horng; Liang, Cher‐Wei; Hsu, Lee-Fen; Li, Shuyu; Wang, Moo–Chin; Yen, Feng‐Lin; Lee, Chiang‐Wen

doi:10.1016/j.jep.2013.10.054

Cited by 70 publications

(45 citation statements)

References 25 publications

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“…Whereas methoxy flavones do competitively inhibit tyrosinase, their application in cosmetic or medicinal products that aim to decrease tyrosine or dopamine oxidation should be treated with caution. Experiments with murine B16/F10 melanoma cells have shown that treatment with polyhydroxy flavones results in reduced melanogenesis but that polymethoxy flavones affect cell signalling, and induce tyrosinase expression and melanogenesis . However, similar experiments with humans rather than murine melanocytes have shown that polymethoxy flavones inhibit the induction of melanogenesis …”

Section: Resultsmentioning

confidence: 99%

“…Experiments with murine B16/F10 melanoma cells have shown that treatment with polyhydroxy flavones results in reduced melanogenesis 45,46 but that polymethoxy flavones affect cell signalling, and induce tyrosinase expression and melanogenesis. [45][46][47][48][49][50][51][52] However, similar experiments with humans rather than murine melanocytes have shown that polymethoxy flavones inhibit the induction of melanogenesis. 53 ORCID Randolph R.J. Arroo https://orcid.org/0000-0002-0672-7927…”

Section: Molecular Docking To Mushroom Tyrosinasementioning

confidence: 99%

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Flavones as tyrosinase inhibitors: kinetic studies in vitro and in silico

Arroo

Sarı

Barut

et al. 2020

Phytochemical Analysis

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Introduction Tyrosinase is a multifunctional copper‐containing oxidase enzyme that catalyses the first steps in the formation of melanin pigments. Identification of tyrosinase inhibitors is of value for applications in cosmetics, medicine and agriculture. Objective To develop an analytical method that allows identification of drug‐like natural products that can be further developed as tyrosinase inhibitors. Results of in vitro and in silico studies will be compared in order to gain a deeper insight into the mechanism of action of enzyme inhibition. Method Using an in vitro assay we tested tyrosinase inhibitor effects of five structurally related flavones, i.e. luteolin (1), eupafolin (2), genkwanin (3), nobiletin (4), and chrysosplenetin (5). The strongest inhibitors were further investigated in silico, using enzyme docking simulations. Results All compounds tested showed modest tyrosinase inhibitory effect compared to the positive control, kojic acid. The polymethoxy flavones 4 and 5 exhibited the strongest tyrosinase inhibitory effect with the half maximal inhibitory concentration (IC50) values of 131.92 ± 1.75 μM and 99.87 ± 2.38 μM respectively. According to kinetic analysis 2, 4 and 5 were competitive inhibitors, whereas 1 and 3 were non‐competitive inhibitors of tyrosinase. Docking studies indicated that methoxy groups on 4 and 5 caused steric hindrance which prevented alternative binding modes in the tyrosinase; the methoxy groups on the B‐ring of these flavones faced the catalytic site in the enzyme. Conclusions The docking simulations nicely complemented the in vitro kinetic studies, opening the way for the development of predictive models for use in drug design.

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Section: Resultsmentioning

confidence: 99%

Section: Molecular Docking To Mushroom Tyrosinasementioning

confidence: 99%

Flavones as tyrosinase inhibitors: kinetic studies in vitro and in silico

Arroo

Sarı

Barut

et al. 2020

Phytochemical Analysis

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“…Particularly, protein homogenates were separated by SDS—PAGE and transferred to a membrane (ie, nitrocellulose, polyvinylidene fluoride [PVDF]), then with antibodies of interest (ie, monoclonal/polyclonal of TYR, TRP1, TRP2, MITF, p‐CREB, p‐ERK, p‐p38, p‐Akt) as well as α‐tubulin, b‐actin, and GAPDH for internal control. Upon further reaction with secondary antibodies and chemiluminescence reagents, the intensity of developed immunoblots was quantified by a software (ie, Jeldoc2000, AlphaImager HP system, G:BOX Chemi, ImageJ program, FluorChem® FC2, LAS‐1000 lumino‐image analyzer, Image MasterTM 2D Elite software, UVIpro Platinum 1.1) …”

Section: Protocol and Assaysmentioning

confidence: 99%

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

Lajis

Ariff

2019

J of Cosmetic Dermatology

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Summary Human skin pigmentation is a result of constitutive and facultative pigmentation. Facultative pigmentation is frequently stimulated by UV radiation, pharmacologic drugs, and hormones whereby leads to the development of abnormal skin hyperpigmentation. To date, many state‐of‐art depigmenting compounds have been studied using in vitro model to treat hyperpigmentation problems for cosmetic dermatological applications; little attention has been made to compare the effectiveness of these depigmenting compounds and their mode of actions. In this present article, new and recent depigmenting compounds, their melanogenic pathway targets, and modes of action are reviewed. This article compares the effectiveness of these new depigmenting compounds to modulate several melanogenesis‐regulatory enzymes and proteins such as tyrosinase (TYR), TYR‐related protein‐1 (TRP1), TYR‐related protein‐2 (TRP2), microphthalmia‐associated transcription factor (MITF), extracellular signal—regulated kinase (ERK) and N‐terminal kinases (JNK) and mitogen‐activated protein kinase p38 (p38 MAPK). Other evidences from in vitro assays such as inhibition on melanosomal transfer, proteasomes, nitric oxide, and inflammation‐induced melanogenesis are also highlighted. This article also reviews analytical techniques in different assays performed using in vitro model as well as their advantages and limitations. This article also provides an insight on recent finding and re‐examination of some protocols as well as their effectiveness and reliability in the evaluation of depigmenting compounds. Evidence and support from related patents are also incorporated in this present article to give an overview on current patented technology, latest trends, and intellectual values of some depigmenting compounds and protocols, which are rarely highlighted in the literatures.

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“…Effects of Mansonone E on the Phosphorylation Levels of Intracellular Signal Transduction-Related Proteins Melanogenesis-related proteins are known to be regulated by intracellular signaling proteins such as Akt and MAPKs, 27) which are activated by phosphorylation. Therefore, phosphorylation levels of intracellular signaling-related proteins were measured 30 min after addition of α-MSH and mansonone E.…”

Section: Fig 2 Effects Of Mansonone E On the Level Of Melanogenesismentioning

confidence: 99%

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

Nishina

Miura

Goto

et al. 2018

Biological & Pharmaceutical Bulletin

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Many natural products that inhibit melanogenesis, freckles, and hyperpigmentation have been selectively used in cosmetics because melanogenesis is linked to the multiple biogenesis cascades of melanin synthesis. However, some of these compounds have side effects that may result in their restriction in the future. We report here the isolation and structural elucidation of compounds extracted from Mansonia gagei and evaluate their activity on melanogenesis inhibition. We isolated five known compounds from M. gagei and identified them as mansonone E (1), mansorin I (2), populene F (3), mansonone G (4), and mansorin B (5). After evaluating the five compounds for cytotoxicity against B16 cells and inhibitory activity on α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis, we determined that the cytotoxicity and melanogenesis-inhibitory effect of 1 were relatively low and high, respectively. Next, the effect of 1 on the expression of melanogenesisrelated proteins was assessed; it was confirmed that 1 dose-dependently inhibited the expression levels of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, cAMP response element binding protein (CREB), and microphthalmia-associated transcription factor (MITF) which were increased after stimulation by α-MSH. Furthermore, the effects of 1 on the phosphorylation levels of intracellular signaling pathway-related proteins were evaluated, and it was found that 1 dose-dependently rescued the phosphorylation of Akt and p38 mitogen-activated protein kinases (MAPK), which were up-or down-regulated after stimulation by α-MSH. In contrast, treatment with the phosphoinositide 3-kinase (PI3K)/Akt inhibitor wortmannin enhanced melanogenesis inhibition by mansonone E. Cumulatively, the data suggest that 1 suppresses α-MSH-induced melanogenesis in B16 cells by inhibiting both phosphorylation in the PI3K/Akt pathway and the expression of melanogenesis-related proteins.

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Eupafolin, a skin whitening flavonoid isolated from Phyla nodiflora, downregulated melanogenesis: Role of MAPK and Akt pathways

Cited by 70 publications

References 25 publications

Flavones as tyrosinase inhibitors: kinetic studies in vitro and in silico

Flavones as tyrosinase inhibitors: kinetic studies in vitro and in silico

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

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

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