scholarly journals Di (Isoquinolin-1-Yl) Sulfane (DIQS) Inhibits Melaninogenesis by Modulating PKA/CREB and MAPK Signaling Pathways

Cosmetics ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 104
Author(s):  
Jung Yoon Yang ◽  
Dae-Seop Shin ◽  
Kyu-Seok Hwang ◽  
Seong Soon Kim ◽  
Byung Hoi Lee ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Inhibitory Effect ◽  
Camp Response Element Binding ◽  
Mapk Signaling ◽  
Mass Spectrometry Analysis ◽  
Zebrafish Embryos ◽  
Synthetic Compound ◽  
Spectrometry Analysis ◽  
B16f10 Cells ◽  
Element Binding Protein

The novel synthetic compound Di (isoquinolin-1-yl) sulfane (DIQS) was identified by zebrafish larva screening during the development of an agent to inhibit abnormal hyperpigmentation. In this study, we investigated the inhibitory effect of DIQS on melanogenesis and its underlying mechanism. DIQS inhibited melanin production and tyrosinase activity in B16F10 cells stimulated with α-melanocyte-stimulating hormone (α-MSH), as well as zebrafish embryos and reconstituted human skin tissue containing melanocytes. DIQS decreased the mRNA and protein expression of microphthalmia-associated transcription factor (MITF) and tyrosinase at a concentration of 10 μM. DIQS also inhibited the phosphorylation of cAMP response element-binding protein (CREB) and p-p38 and p-JNK stimulated by α-MSH. These results suggest that DIQS attenuates hyperpigmentation via inhibition of the cAMP/PKA/CREB/MITF/tyrosinase axis and MAPK pathways. Liquid chromatography–tandem mass spectrometry analysis revealed that DIQS blocked the conversion of tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in zebrafish embryos. Finally, we confirmed that DIQS was non-toxic in reconstituted human tissues such as the epidermis, used to test skin sensitization, and the cornea, used to test eye irritation. In summary, the results of this study suggest the potential of DIQS as a small-molecule agent for skin-whitening cosmetics and the treatment of hyperpigmentation disorders without biological toxicity.

scholarly journals Arachidonic Acid Inhibits Epithelial Na Channel Via Cytochrome P450 (CYP) Epoxygenase-dependent Metabolic Pathways

2004 ◽  
Vol 124 (6) ◽  
pp. 719-727 ◽  
Author(s):  
Yuan Wei ◽  
Dao-Hong Lin ◽  
Rowena Kemp ◽  
Ganesh S.S. Yaddanapudi ◽  
Alberto Nasjletti ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Na Channel ◽  
Cortical Collecting Duct ◽  
Patch Clamp Technique ◽  
Spectrometry Analysis

We used the patch-clamp technique to study the effect of arachidonic acid (AA) on epithelial Na channels (ENaC) in the rat cortical collecting duct (CCD). Application of 10 μM AA decreased the ENaC activity defined by NPo from 1.0 to 0.1. The dose–response curve of the AA effect on ENaC shows that 2 μM AA inhibited the ENaC activity by 50%. The effect of AA on ENaC is specific because neither 5,8,11,14-eicosatetraynoic acid (ETYA), a nonmetabolized analogue of AA, nor 11,14,17-eicosatrienoic acid mimicked the inhibitory effect of AA on ENaC. Moreover, inhibition of either cyclooxygenase (COX) with indomethacin or cytochrome P450 (CYP) ω-hydroxylation with N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) failed to abolish the effect of AA on ENaC. In contrast, the inhibitory effect of AA on ENaC was absent in the presence of N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide (MS-PPOH), an agent that inhibits CYP-epoxygenase activity. The notion that the inhibitory effect of AA is mediated by CYP-epoxygenase–dependent metabolites is also supported by the observation that application of 200 nM 11,12-epoxyeicosatrienoic acid (EET) inhibited ENaC in the CCD. In contrast, addition of 5,6-, 8,9-, or 14,15-EET failed to decrease ENaC activity. Also, application of 11,12-EET can still reduce ENaC activity in the presence of MS-PPOH, suggesting that 11,12-EET is a mediator for the AA-induced inhibition of ENaC. Furthermore, gas chromatography mass spectrometry analysis detected the presence of 11,12-EET in the CCD and CYP2C23 is expressed in the principal cells of the CCD. We conclude that AA inhibits ENaC activity in the CCD and that the effect of AA is mediated by a CYP-epoxygenase–dependent metabolite, 11,12-EET.

scholarly journals Interaction between PHB2 and Enterovirus A71 VP1 Induces Autophagy and Affects EV-A71 Infection

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 414 ◽  
Author(s):  
Weitao Su ◽  
Shan Huang ◽  
Huimin Zhu ◽  
Bao Zhang ◽  
Xianbo Wu
Keyword(s):  
Defense Mechanism ◽  
Foot And Mouth Disease ◽  
Underlying Mechanism ◽  
Host Protein ◽  
Mass Spectrometry Analysis ◽  
Structural Protein ◽  
Viral Protein Synthesis ◽  
Spectrometry Analysis ◽  
C Terminus ◽  
Enterovirus A71

Enterovirus A71 (EV-A71) is a major pathogen that causes severe and fatal cases of hand-foot-and-mouth disease (HFMD). HFMD caused by EV-A71 seriously endangers children’s health. Although autophagy is an important antiviral defense mechanism, some viruses have evolved strategies to utilize autophagy to promote self-replication. EV-A71 can utilize autophagy vesicles as replication scaffolds, indicating that EV-A71 infection is closely related to its autophagy induction mechanism. VP1, a structural protein of EV-A71, has been reported to induce autophagy, but the underlying mechanism is still unclear. In this study, we found that the C-terminus (aa 251–297) of VP1 induces autophagy. Mass spectrometry analysis suggested that prohibitin 2 (PHB2) interacts with the C-terminus of the EV-A71 VP1 protein, and this was further verified by coimmunoprecipitation assays. After PHB2 knockdown, EV-A71 replication, viral particle release, and viral protein synthesis were reduced, and autophagy was inhibited. The results suggest that PHB2 interaction with VP1 is essential for induction of autophagy and the infectivity of EV-A71. Furthermore, we confirmed that EV-A71 induced complete autophagy that required autolysosomal acidification, thus affecting EV-A71 infection. In summary, this study revealed that the host protein PHB2 is involved in an autophagy mechanism during EV-A71 infection.

scholarly journals Impact of Piper betle leaf extract on grape downy mildew: effects of combining 4-allylpyrocatechol with eugenol, α-pinene or β-pinene

2018 ◽  
Vol 55 (No. 1) ◽  
pp. 23-30
Author(s):  
Aoki Yoshinao ◽  
Trung Nguyen Van ◽  
Suzuki Shunji
Keyword(s):  
Downy Mildew ◽  
Methanol Extract ◽  
Inhibitory Effect ◽  
Mass Spectrometry Analysis ◽  
Piper Betle ◽  
Gas Chromatograph ◽  
Inhibitory Effects ◽  
Spectrometry Analysis ◽  
Tandem Mass Spectrometry Analysis ◽  
Grape Downy Mildew

Methanol extract of Piper betle leaves exhibited an inhibitory effect on grape downy mildew. This extract might contain more than two compounds which have different polarities that suppress grape downy mildew. Gas chromatograph-tandem mass spectrometry analysis identified 4-allylpyrocatechol, eugenol, α-pinene, and β-pinene in the methanol extract. Neither of the compounds suppressed grape downy mildew by single treatment. On the other hand, treatment with a combination of 4-allylpyrocatechol with eugenol, α-pinene or β-pinene enhanced the inhibitory effects on grape downy mildew and perfectly suppressed it. The complex extracted from P. betle leaves may be used in organic agriculture as an alternative to chemical fungicides in viticulture.

scholarly journals Phytochemistry, gas chromatography-mass spectrometry analysis and in vitro anti-bacterial activities of Desplatsia dewevrei (De Wild. & T. Durand)

2018 ◽  
Vol 5 (10) ◽  
pp. 373-404
Author(s):  
Oghale Ovuakporie-Uvo ◽  
MacDonald Idu ◽  
Anne O. Itemire
Keyword(s):  
Inhibitory Effect ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Useful Plants ◽  
Zone Of Inhibition ◽  
Spectrometry Analysis ◽  
Gram Positive Bacteria ◽  
Quantitative Analyses ◽  
Bacterial Effect

Phytochemicals have been reported to have direct and/or indirect influence on the antibacterial potentials of useful plants. The present study was aimed at determining the phyto-components by traditional methods and GC-MS analysis alongside testing the anti-bacterial activities of Desplatsia dewevrei leaves and fruits. The maceration of 500 g of Desplatsia dewevrei powder in methanol yielded 5.7 g of extract. Qualitatively coumarins were found to be richly present in the leaves while, quinones were most evidently present in the fruits of Desplatsia dewevrei. Quantitative analyses show that the phenolic and tannic acid contents of Desplatsia dewevrei may be the chief compounds responsible for the antibacterial activity of the plant. GC-MS results of Desplatsia dewevrei fruits and leaves respectively showed Gas Chromatograms having 33 and 63 peaks representing different phyto-compounds. Of the 33 and 63 phyto-compounds, Cyclohexanepropanol, alpha.,2,2,6-tetrame-thyl and Farnesyl bromide were recurrent at different retention time. Although Desplatsia dewevrei showed no zone of inhibition for gram negative bacteria, its inhibitory effect on gram positive bacteria is significant. In conclusion, D. dewevrei is a phytochemical rich plant. However, a further study on the anti-bacterial effect of Desplatsia dewevrei using solvent extracts other than methanol is recommended for future incorporation in drug development.

scholarly journals Fatty Acids from Plasmodium falciparum Down-Regulate the Toxic Activity of Malaria Glycosylphosphatidylinositols

2006 ◽  
Vol 74 (10) ◽  
pp. 5487-5496 ◽  
Author(s):  
Françoise Debierre-Grockiego ◽  
Louis Schofield ◽  
Nahid Azzouz ◽  
Jörg Schmidt ◽  
Cristiana Santos de Macedo ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Plasmodium Falciparum ◽  
Single Molecule ◽  
Inhibitory Effect ◽  
Exchange Chromatography ◽  
Mass Spectrometry Analysis ◽  
Necrosis Factor Alpha ◽  
Toxic Activity ◽  
Spectrometry Analysis ◽  
Tnf Α

ABSTRACT Plasmodium falciparum malaria kills roughly 2.5 million people, mainly children, annually. Much of this mortality is thought to arise from the actions of a malarial toxin. This toxin, identified as glycosylphosphatidylinositol (GPI), is a major pathogenicity determinant in malaria. A malarial molecule, Pfj, labeled by [3H]glucosamine like the GPIs, was identified as a non-GPI molecule. Here we show that Pfj is able to down-regulate tumor necrosis factor alpha (TNF-α) production induced by the GPI of P. falciparum. Mass spectrometry analysis showed that Pfj was not a single molecule but represented a number of molecules. Separation methods, such as cation-exchange chromatography and thin-layer chromatography, were used to isolate and identify the following four main fatty acids responsible for the inhibitory effect on TNF-α production: myristic, pentadecanoic, palmitic, and palmitoleic acids. This regulatory effect on cytokine production suggests that there is balanced bioactivity for the different categories of malarial lipids.

scholarly journals Protocatechuic Aldehyde Inhibits α-MSH-Induced Melanogenesis in B16F10 Melanoma Cells via PKA/CREB–Associated MITF Downregulation

2021 ◽  
Vol 22 (8) ◽  
pp. 3861
Author(s):  
Seok-Chun Ko ◽  
Seung-Hong Lee
Keyword(s):  
Molecular Mechanisms ◽  
3D Structure ◽  
Camp Response Element Binding ◽  
Melanoma Cells ◽  
Dependent Manner ◽  
Camp Response Element ◽  
B16f10 Cells ◽  
Protocatechuic Aldehyde ◽  
Element Binding Protein ◽  
Dependent Protein

Protocatechuic aldehyde (PA) is a naturally occurring phenolic compound that is a potent inhibitor of mushroom tyrosinase. However, the molecular mechanisms of the anti-melanogenesis activity of PA have not yet been reported. The aim of the current study was to clarify the melanogenesis inhibitory effects of PA and its molecular mechanisms in murine melanoma cells (B16F10). We first predicted the 3D structure of tyrosinase and used a molecular docking algorithm to simulate binding between tyrosinase and PA. These molecular modeling studies calculated a binding energy of −527.42 kcal/mol and indicated that PA interacts with Cu400 and 401, Val283, and His263. Furthermore, PA significantly decreased α-MSH-induced intracellular tyrosinase activity and melanin content in a dose-dependent manner. PA also inhibited key melanogenic proteins such as tyrosinase, tyrosinase-related protein 1 (TRP-1), and TRP-2 in α-MSH-stimulated B16F10 cells. In addition, PA decreased MITF expression levels by inhibiting phosphorylation of cAMP response element-binding protein (CREB) and cAMP-dependent protein kinase A (PKA). These results demonstrate that PA can effectively suppress melanin synthesis in melanoma cells. Taken together, our results show that PA could serve as a potential inhibitor of melanogenesis, and hence could be explored as a possible skin-lightening agent.

scholarly journals Extracts ofArtocarpus communisDecreaseα-Melanocyte Stimulating Hormone-Induced Melanogenesis through Activation of ERK and JNK Signaling Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-Tzu Fu ◽  
Chiang-Wen Lee ◽  
Horng-Huey Ko ◽  
Feng-Lin Yen
Keyword(s):  
Skin Diseases ◽  
Folk Medicine ◽  
Camp Response Element Binding ◽  
Melanin Content ◽  
Agricultural Plant ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Cells ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
Stimulating Hormone

Artocarpus communisis an agricultural plant that is also used in folk medicine to prevent skin diseases, including acne and dermatitis. Extracts ofA. communishave been used to effectively inhibit melanogenesis; however, the antimelanogenesis mechanism of these extracts has not yet been investigated. The present study utilized a cell-free tyrosinase assay as well asα-melanocyte stimulating hormone- (-MSH-) induced tyrosinase assay conducted in B16F10 cells, performed a cytotoxicity assay, and determined cellular melanin content to examine the effects of a methanolic extract ofA. communis(ACM) and various organic partition fractions ofA. communison melanogenesis. In addition, we performed western blot analysis to elucidate the mechanism of their antimelanogenesis effect. Our results indicated that, except for the n-hexane extract, ACM and the various partition extracts at noncytotoxic concentrations effectively decreased melanin content and tyrosinase activity by downregulating microphthalmia-associated transcription factor (MITF) and phosphorylated cAMP response element-binding protein (p-CREB). Moreover, ACM and the partition fractions activated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) to inhibit the synthesis of MITF and finally to decrease melanin production. In conclusion, we suggest that noncytotoxic concentrations of ACM and the various partition fractions may be useful as references for developing skin-lighting agents for use in medicines or cosmetics.

scholarly journals Neuronal energy-sensing pathway promotes energy balance by modulating disease tolerance

2016 ◽  
Vol 113 (23) ◽  
pp. E3307-E3314 ◽  
Author(s):  
Run Shen ◽  
Biao Wang ◽  
Maria G. Giribaldi ◽  
Janelle Ayres ◽  
John B. Thomas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Energy Homeostasis ◽  
Underlying Mechanism ◽  
Free Food ◽  
Camp Response Element Binding ◽  
Balance Growth ◽  
Starvation Resistance ◽  
Epithelial Integrity ◽  
Element Binding Protein

The starvation-inducible coactivator cAMP response element binding protein (CREB)–cAMP-regulated transcription coactivator (Crtc) has been shown to promote starvation resistance in Drosophila by up-regulating CREB target gene expression in neurons, although the underlying mechanism is unclear. We found that Crtc and its binding partner CREB enhance energy homeostasis by stimulating the expression of short neuropeptide F (sNPF), an ortholog of mammalian neuropeptide Y, which we show here is a direct target of CREB and Crtc. Neuronal sNPF was found to promote energy homeostasis via gut enterocyte sNPF receptors, which appear to maintain gut epithelial integrity. Loss of Crtc–sNPF signaling disrupted epithelial tight junctions, allowing resident gut flora to promote chronic increases in antimicrobial peptide (AMP) gene expression that compromised energy balance. Growth on germ-free food reduced AMP gene expression and rescued starvation sensitivity in Crtc mutant flies. Overexpression of Crtc or sNPF in neurons of wild-type flies dampens the gut immune response and enhances starvation resistance. Our results reveal a previously unidentified tolerance defense strategy involving a brain–gut pathway that maintains homeostasis through its effects on epithelial integrity.

Anti-Melanogenic Activity of p-Chlorophenyl Benzyl Ether in α-MSH-Induced Mouse Melanoma B16F10 Cells

2019 ◽  
Vol 819 ◽  
pp. 118-123
Author(s):  
Wassana Riam-Amatakun ◽  
Panupan Limpachayaporn ◽  
Jhoan Rhea L. Pizon ◽  
Praneet Opanasopit ◽  
Nopparat Nuntharatanapon
Keyword(s):  
Kojic Acid ◽  
Positive Association ◽  
Inhibitory Effect ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Benzyl Ether ◽  
Melanin Content ◽  
Synthetic Compound ◽  
Melanin Biosynthesis ◽  
B16f10 Cells

Melanin is cutaneous pigment which level of its production determines skin complexion. Overproduction of melanin, frequently promoted by UV rays, results in darkening of the skin. Inhibition of tyrosinase activity, a core component in melanin biosynthesis, is one of the mechanisms of depigmenting agents. Hydroquinone and kojic acid are the examples of well-known whitening agents widely used in both pharmaceutical and cosmetic products. However, their adverse effect issues still needed to be overcome. A recent study showed that p-chlorophenyl benzyl ether (Cl-benz), a new synthetic compound, more strongly inhibited mushroom tyrosinase than kojic acid. In the current study, cytotoxicity, anti-melanogenic activity and anti-tyrosinase activity of Cl-benz were performed in mouse B16F10 melanoma cells compared to kojic acid. After 24 h of treatment on B16F10 cells, the cytotoxicity was not observed with Cl-benz and kojic acid. However, after incubation for 48 h, kojic acid at a concentration of 500 μM reduced cell viability less than 50%, whereas Cl-benz-treated cells showed negligible cytotoxicity. For cell-based assay, Cl-benz exhibited inhibitory effect similar to kojic acid. Melanin production in B16F10 cells was suppressed by Cl-benz in a dose dependent manner. One hundred micrograms of Cl-benz decreased melanin content in α-MSH by 66%. Moreover, the percentage of cellular tyrosinase activity of Cl-benz showed positive association with its corresponding melanin content. These results revealed that Cl-benz could inhibit melanogenesis via the mechanism of cellular tyrosinase inhibition. Accordingly, Cl-benz has potential to become a novel skin whitening agent in terms of efficacy and safety.

scholarly journals Xiao Yao San Improves Depressive-Like Behavior in Rats through Modulation ofβ-Arrestin 2-Mediated Pathways in Hippocampus

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Xiaoxia Zhu ◽  
Oudong Xia ◽  
Weili Han ◽  
Meng Shao ◽  
Linlin Jing ◽  
...  
Keyword(s):  
Social Isolation ◽  
High Performance ◽  
Mammalian Target Of Rapamycin ◽  
Underlying Mechanism ◽  
Mass Spectrometry Analysis ◽  
Mild Stress ◽  
Spectrometry Analysis ◽  
Phosphatase 2A ◽  
Classical Chinese Medicine ◽  
Tyrosine Receptor Kinase

Xiao Yao San (XYS) is a classical Chinese medicine formula that has been widely used to treat mood disorders for hundreds of years. To confirm the effect of XYS and better understand its underlying mechanism, high-performance liquid chromatography-mass spectrometry analysis-based quality control of XYS extracts and proteomics-based identification of differential proteins in the hippocampus were adopted in social isolation and chronic unpredictable mild stress- (CUMS-) treated rats. The depressive-like behavior of rats induced by CUMS resembled the manifestation of human depression. The upregulated corticosterone (CORT) and urocortin 2 (UCN2) levels demonstrated the existence of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. XYS was effective in ameliorating the depressive-like behavior and downregulating UCN2 and CORT. XYS decreased the expression of serine/threonine-protein phosphatase 2A subunit B and increased the expression ofβ-arrestin 2. The expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and mammalian target of rapamycin (mTOR) were also elevated by XYS. In conclusion, XYS improves social isolation and CUMS-induced depressive-like behavior and ameliorates HPA hyperactivation through the downregulation of corticotrophin releasing hormone (CRH) receptor 2. The upregulation of BDNF/TrkB and the phosphorylation of mTOR requireβ-arrestin 2 as a scaffold to regulate stress signaling.

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