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1.
Plant Physiol ; 195(3): 2053-2072, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38536032

RESUMO

Carotenoids are major pigments contributing to fruit coloration. We previously reported that the apple (Malus domestica Borkh.) mutant fruits of "Beni Shogun" and "Yanfu 3" show a marked difference in fruit coloration. However, the regulatory mechanism underlying this phenomenon remains unclear. In this study, we determined that carotenoid is the main factor influencing fruit flesh color. We identified an R1-type MYB transcription factor (TF), MdMYBS1, which was found to be highly associated with carotenoids and abscisic acid (ABA) contents of apple fruits. Overexpression of MdMYBS1 promoted, and silencing of MdMYBS1 repressed, ß-branch carotenoids synthesis and ABA accumulation. MdMYBS1 regulates carotenoid biosynthesis by directly activating the major carotenoid biosynthetic genes encoding phytoene synthase (MdPSY2-1) and lycopene ß-cyclase (MdLCYb). 9-cis-epoxycarotenoid dioxygenase 1 (MdNCED1) contributes to ABA biosynthesis, and MdMYBS1 enhances endogenous ABA accumulation by activating the MdNCED1 promoter. In addition, the basic leucine zipper domain TF ABSCISIC ACID-INSENSITIVE5 (MdABI5) was identified as an upstream activator of MdMYBS1, which promotes carotenoid and ABA accumulation. Furthermore, ABA promotes carotenoid biosynthesis and enhances MdMYBS1 and MdABI5 promoter activities. Our findings demonstrate that the MdABI5-MdMYBS1 cascade activated by ABA regulates carotenoid-derived fruit coloration and ABA accumulation in apple, providing avenues in breeding and planting for improvement of fruit coloration and quality.


Assuntos
Ácido Abscísico , Carotenoides , Frutas , Regulação da Expressão Gênica de Plantas , Malus , Proteínas de Plantas , Fatores de Transcrição , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Malus/genética , Malus/metabolismo , Malus/efeitos dos fármacos , Carotenoides/metabolismo , Frutas/genética , Frutas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Pigmentação/genética , Pigmentação/efeitos dos fármacos
2.
Sensors (Basel) ; 24(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38676043

RESUMO

The Polar Qualification System (PQS) was applied on hue spectra fingerprinting to describe color changes in tomato during storage. The cultivar 'Pitenza' was harvested at six different maturity stages, and half of the samples were subjected to gaseous 1-methylcyclopropene (1-MCP) treatment. Reference color parameters were recorded with a vision system colorimeter instrument, and the fruit pigment concentration was assessed with the DA-index®. Additionally, acoustic firmness (Stiffness) was measured. All acquired reference parameters were used to grade fruit in the supply chain. The applied 1-MCP treatments were used to control the ripening of climacteric horticultural produce. Both the DA-index® and stiffness values, presented as chlorophyll concentration and acoustic firmness, showed significant differences among maturity stages and treated and control samples and in their kinetics during storage. The machine vision parameter PQS-X was significantly affected by 1-MCP treatment (F = 10.18, p < 0.01), while PQS-Y was primarily affected by storage time (F = 18.18, p < 0.01) and maturity stage (F = 11.15, p < 0.01). A significant correlation was achieved for acoustic firmness with normalized color (r > 0.78) and PQS-Y (r > 0.80), as well as for the DA-index® (r > 0.9). The observed color changes agreed with the reference measurements. The significant statistical effect on the PQS coordinates suggests that hue spectra fingerprinting with this data compression technique is suitable for quality assessment based on color.


Assuntos
Cor , Ciclopropanos , Solanum lycopersicum , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/química , Solanum lycopersicum/crescimento & desenvolvimento , Ciclopropanos/farmacologia , Frutas/química , Frutas/efeitos dos fármacos , Pigmentação/efeitos dos fármacos , Pigmentação/fisiologia , Clorofila/análise , Clorofila/metabolismo , Pigmentos Biológicos/análise
3.
Exp Dermatol ; 31(1): 57-63, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32391926

RESUMO

We conducted large-scale screening test on drugs that were already approved for other diseases to find pigmentation-modulating agents. Among drugs with potential for pigmentation control, we selected sorafenib and further investigated the effect on pigmentation using HM3KO melanoma cells. As a result of treating melanoma cells with sorafenib, pigmentation was promoted in terms of melanin content and tyrosinase activity. Sorafenib increased mRNA and protein levels of pigmentation-related genes such as MITF, tyrosinase and TRP1. To uncover the action mechanism, we investigated the effect of sorafenib on the intracellular signalling pathways. Sorafenib reduced phosphorylation of AKT and ERK, suggesting that sorafenib induces pigmentation through inhibition of the AKT and ERK pathways. In addition, sorafenib significantly increased the level of active ß-catenin, together with activation of ß-catenin signalling. Mechanistic study revealed that sorafenib decreased phosphorylation of serine 9 (S9) of GSK3ß, while it increased phosphorylation of tyrosine 216 (Y216) of GSK3ß. These results suggest that sorafenib activates the ß-catenin signalling through the regulation of GSK3ß phosphorylation, thereby affecting the pigmentation process.


Assuntos
Antineoplásicos/farmacologia , Melanoma/patologia , Pigmentação/efeitos dos fármacos , Neoplasias Cutâneas/patologia , Sorafenibe/farmacologia , beta Catenina/metabolismo , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Humanos , Transdução de Sinais/efeitos dos fármacos , Sorafenibe/metabolismo
4.
Mar Drugs ; 20(2)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35200653

RESUMO

Melanin synthesis is a defense mechanism that prevents skin damage, but excessive accumulation of melanin occurs in the skin in various reactions such as pigmentation, lentigines, and freckles. Although anti-melanogenic effects have been demonstrated for various naturally occurring marine products that inhibit and control tyrosinase activity, most studies have not been extended to in vivo applications. Phlorofucofuroeckol-A (PFF-A, 12.5-100 µM) isolated from Ecklonia cava has previously been shown to have tyrosinase-mitigative effects in B16F10 cells, but it has not been evaluated in an in vivo model, and its underlying mechanism for anti-melanogenic effects has not been studied. In the present study, we evaluated the safety and efficacy of PFF-A for anti-melanogenic effects in an in vivo model. We selected low doses of PFF-A (1.5-15 nM) and investigated their mitigative effects on pigmentation stimulated by α-MSH in vivo and their related-mechanism in an in vitro model. The findings suggest that low-dose PFF-A derived from E. cava suppresses pigmentation in vivo and melanogenesis in vitro. Therefore, this study presents the possibility that PFF-A could be utilized as a new anti-melanogenic agent in the cosmeceutical industries.


Assuntos
Benzofuranos/farmacologia , Dioxinas/farmacologia , Melaninas/biossíntese , Phaeophyceae/química , Pigmentação/efeitos dos fármacos , Animais , Benzofuranos/administração & dosagem , Benzofuranos/isolamento & purificação , Linhagem Celular Tumoral , Dioxinas/administração & dosagem , Dioxinas/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Masculino , Melanoma Experimental/metabolismo , Camundongos , Peixe-Zebra , alfa-MSH/metabolismo
5.
Development ; 145(21)2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30254141

RESUMO

In mammalian albinism, disrupted melanogenesis in the retinal pigment epithelium (RPE) is associated with fewer retinal ganglion cells (RGCs) projecting ipsilaterally to the brain, resulting in numerous abnormalities in the retina and visual pathway, especially binocular vision. To further understand the molecular link between disrupted RPE and a reduced ipsilateral RGC projection in albinism, we compared gene expression in the embryonic albino and pigmented mouse RPE. We found that the Wnt pathway, which directs peripheral retinal differentiation and, generally, cell proliferation, is dysregulated in the albino RPE. Wnt2b expression is expanded in the albino RPE compared with the pigmented RPE, and the expanded region adjoins the site of ipsilateral RGC neurogenesis and settling. Pharmacological activation of Wnt signaling in pigmented mice by lithium (Li+) treatment in vivo reduces the number of Zic2-positive RGCs, which are normally fated to project ipsilaterally, to numbers observed in the albino retina. These results implicate Wnt signaling from the RPE to neural retina as a potential factor in the regulation of ipsilateral RGC production, and thus the albino phenotype.


Assuntos
Pigmentação , Células Ganglionares da Retina/metabolismo , Via de Sinalização Wnt , Albinismo/genética , Albinismo/patologia , Animais , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Conexina 43/metabolismo , Embrião de Mamíferos/citologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Lítio/farmacologia , Camundongos , Neurogênese/efeitos dos fármacos , Pigmentação/efeitos dos fármacos , Células Ganglionares da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
6.
J Exp Zool B Mol Dev Evol ; 336(4): 352-363, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33465290

RESUMO

Crustacyanin has the function of binding astaxanthin which is the best antioxidant, and plays an important role in the body color variation of crustaceans. To investigate the causes of body color variation of the ridgetail white prawn, Exopalaemon carinicauda, the present study obtained four subtypes of crustacyanin gene: C1, C2, A1, and A2. Based on fluorescence quantitative polymerase chain reaction, lipocalin-C1 is mainly expressed in the eyestalk, lipocalin-C2 is in the ventral nerve cord, and lipocalin-A1 and lipocalin-A2 are in subcutaneous adipose tissues. Under the inhibiting effect of Cd2+ stress, the expression of four subtypes first increases and then decreases within 24 h, and reaches the maximum at 6 or 12 h. RNA interference experiments showed a decrease in the expression of lipocalin genes in subcutaneous adipose tissue for each subtype, with the body color changing from transparent to red, and the dark red spots on the epidermis changing to bright red. Moreover, the blue protein in the subcutaneous adipose tissue largely disappeared, based on the light micrographs. In view of these findings, the crustacyanin gene appears to fulfill some function in the resistance to heavy metal stress and body color formation of E. carinicauda.


Assuntos
Cádmio/toxicidade , Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Metais Pesados/toxicidade , Palaemonidae/metabolismo , Pigmentação/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Proteínas de Transporte/genética , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Lipocalinas/genética , Lipocalinas/metabolismo , Palaemonidae/genética , Filogenia , Pigmentação/fisiologia , RNA/genética , RNA/metabolismo , Interferência de RNA
7.
BMC Microbiol ; 21(1): 67, 2021 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-33639851

RESUMO

BACKGROUND: In recent years, clinical Staphylococcus aureus isolates have become highly resistant to antibiotics, which has raised concerns about the ability to control infections by these organisms. The aim of this study was to clarify the effect of a new small molecule, ZY-214-4 (C19H11BrNO4), on S. aureus pigment production. RESULTS: At the concentration of 4 µg/mL, ZY-214-4 exerted a significant inhibitory effect on S. aureus pigment synthesis, without affecting its growth or inducing a toxic effect on the silkworm. An oxidant sensitivity test and a whole-blood killing test indicated that the S. aureus survival rate decreased significantly with ZY-214-4 treatment. Additionally, ZY-214-4 administration significantly reduced the expression of a pigment synthesis-related gene (crtM) and the superoxide dismutase genes (sodA) as determined by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. ZY-214-4 treatment also improved the survival rate of S. aureus-infected silkworm larvae. CONCLUSIONS: The small molecule ZY-214-4 has potential for the prevention of S. aureus infections by reducing the virulence associated with this bacterium.


Assuntos
Pigmentação/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farnesil-Difosfato Farnesiltransferase/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Superóxido Dismutase/genética , Virulência/efeitos dos fármacos
8.
J Pharmacol Sci ; 147(4): 348-357, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34663517

RESUMO

Kaempferol, a representative flavonoid constituent of Sanguisorba officinalis, promotes melanogenesis, but the underlying mechanisms remain unknown. Here, we evaluated the effects of kaempferol on melanocytes morphology and behavior and determined the mechanisms regulating kaempferol-induced pigmentation. We observed that kaempferol increased melanin contents and dendritic length and stimulated melanocyte migration both in vitro and vivo. It significantly enhanced the expression of microphthalmia-associated transcription factor (MITF) and downstream enzymes of melanin biosynthesis-tyrosinase (TYR), tyrosinase-related protein (TRP-1), and dopachrome tautomerase (DCT). It also induced melanosome maturation (increased stage III and IV melanosomes) and melanin transfer to dendritic tips; this was evidenced as follows: kaempferol-treated melanocytes exhibited the perimembranous accumulation of HMB45-positive melanosomes and increased the expression of Rab27A, RhoA, and Cdc42, which improved melanosome transport to perimembranous actin filaments. These results jointly indicated that kaempferol promotes melanogenesis and melanocyte growth. Additionally, kaempferol stimulated the phosphorylation of P38/ERK MAPK and downregulated p-PI3K, p-AKT, and p-P70s6K expression. Pre-incubation with P38 (SB203580) and ERK (PD98059) signaling inhibitors reversed the melanogenic and dendritic effects and MITF expression. PI3K/AKT inhibitor augmented kaempferol-induced melanin content and dendrite length. In summary, kaempferol regulated melanocytes' dendritic growth and melanosome quantity, maturation, and transport via P38/ERK MAPK and PI3K/AKT signaling pathways.


Assuntos
Quempferóis/farmacologia , Melaninas/metabolismo , Melanócitos/citologia , Melanócitos/metabolismo , Melanossomas/metabolismo , Sanguisorba/química , Animais , Transporte Biológico/genética , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Quempferóis/isolamento & purificação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Melanócitos/efeitos dos fármacos , Melanossomas/efeitos dos fármacos , Melanossomas/fisiologia , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Pigmentação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Estimulação Química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Ecotoxicol Environ Saf ; 210: 111850, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33421715

RESUMO

Lead (Pb) is a pervasive global contaminant that interferes with sensitive windows for neurological development and causes oxidative damage to tissues. The effects of moderate and high exposure to Pb have been well-studied in birds, but whether low-level early-life exposure to Pb influences adult phenotype remains unclear. Female songbirds use a male's song and coloration to discriminate between high- and low-quality males. Therefore, if early-life exposure to Pb disrupts song learning ability or shifts the allocation of antioxidant pigments away from colorful secondary sexual traits, male birds exposed to Pb may be less attractive to females. We exposed developing zebra finches (Taeniopygia guttata) to Pb-contaminated drinking water (100 or 1000 parts per billion [ppb]) after hatching (days 0-100). Once male finches reached adulthood (120-150 days post hatch), we measured song learning ability, coloration of bill and cheek patches, and volume of song nuclei in the brain. We also measured female preference for Pb-exposed males relative to control males. Finally, we measured motoric and spatial cognitive performance in male and female finches to assess whether cognitive traits differed in their sensitivity to Pb exposure. Male zebra finches exposed to 1000 ppb Pb had impaired song learning ability, reduced volume of song nuclei, bills with less redness and received less attention from females. Additionally, Pb exposure impaired motoric performance in both male and female finches but did not affect performance in a spatial cognitive task. Adult finches exposed to Pb-contaminated water had higher blood-Pb levels, though in all cases blood-Pb levels were below 7.0 µg dL-1. This study suggests that low-level exposure to Pb contributes to cognitive deficits that persist into adulthood and may indirectly influence fitness by altering secondary sexual traits and reducing male attractiveness.


Assuntos
Poluentes Ambientais/toxicidade , Tentilhões/fisiologia , Chumbo/toxicidade , Animais , Atenção , Cognição/efeitos dos fármacos , Feminino , Aprendizagem/efeitos dos fármacos , Masculino , Fenótipo , Pigmentação/efeitos dos fármacos , Vocalização Animal/efeitos dos fármacos
10.
Int J Mol Sci ; 22(4)2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33562431

RESUMO

Background: Many microRNAs have been identified as critical mediators in the progression of melanoma through its regulation of genes involved in different cellular processes such as melanogenesis, cell cycle control, and senescence. However, microRNAs' concurrent participation in syngeneic mouse B16F1 melanoma cells simultaneously induced decreased proliferation and differential pigmentation by exposure to 5-Brd-2'-dU (5'Bromo-2-deoxyuridine) and L-Tyr (L-Tyrosine) respectively, is poorly understood. Aim: To evaluate changes in the expression of microRNAs and identify which miRNAs in-network may contribute to the functional bases of phenotypes of differential pigmentation and reduction of proliferation in B16F1 melanoma cells exposed to 5-Brd-2'-dU and L-Tyr. Methods: Small RNAseq evaluation of the expression profiles of miRNAs in B16F1 melanoma cells exposed to 5-Brd-2'-dU (2.5 µg/mL) and L-Tyr (5 mM), as well as the expression by qRT-PCR of some molecular targets related to melanogenesis, cell cycle, and senescence. By bioinformatic analysis, we constructed network models of regulation and co-expression of microRNAs. Results: We confirmed that stimulation or repression of melanogenesis with L-Tyr or 5-Brd-2'-dU, respectively, generated changes in melanin concentration, reduction in proliferation, and changes in expression of microRNAs 470-3p, 470-5p, 30d-5p, 129-5p, 148b-3p, 27b-3p, and 211-5p, which presented patterns of coordinated and reciprocal co-expression, related to changes in melanogenesis through their putative targets Mitf, Tyr and Tyrp1, and control of cell cycle and senescence: Cyclin D1, Cdk2, Cdk4, p21, and p27. Conclusions: These findings provide insights into the molecular biology of melanoma of the way miRNAs are coordinated and reciprocal expression that may operate in a network as molecular bases for understanding changes in pigmentation and decreased proliferation induced in B16F1 melanoma cells exposed to L-Tyr and 5-Brd-2'-dU.


Assuntos
Bromodesoxiuridina/farmacologia , Melanoma Experimental/tratamento farmacológico , MicroRNAs/genética , Tirosina/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Senescência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Melaninas/metabolismo , Melanoma Experimental/genética , Melanoma Experimental/patologia , Camundongos , Pigmentação/efeitos dos fármacos , Pigmentação/genética , Pigmentação/fisiologia , RNA-Seq
11.
Molecules ; 26(4)2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33673263

RESUMO

The current research is focused on studying the biological efficacy of flexirubin, a pigment extracted from Chryseobacterium artocarpi CECT 8497.Different methods such as DPPH, H2O2, NO•, O2•-, •OH, lipid peroxidation inhibition by FTC and TBA, ferric reducing and ferrous chelating activity were carried out to evaluate the antioxidant activity of flexirubin. Molecular docking was also carried out, seeking the molecular interactions of flexirubin and a standard antioxidant compound with SOD enzyme to figure out the possible flexirubin activity mechanism. The new findings revealed that the highest level of flexirubin exhibited similar antioxidant activity as that of the standard compound according to the H2O2, •OH, O2•-, FTC and TBA methods. On the other hand, flexirubin at the highest level has shown lower antioxidant activity than the positive control according to the DPPH and NO• and even much lower when measured by the FRAP method. Molecular docking showed that the interaction of flexirubin was in the binding cavity of the SOD enzyme and did not affect its metal-binding site. These results revealed that flexirubin has antioxidant properties and can be a useful therapeutic compound in preventing or treating free radical-related diseases.


Assuntos
Antioxidantes/química , Pigmentos Biológicos/química , Polienos/química , Superóxido Dismutase/química , Compostos de Bifenilo/química , Chryseobacterium/química , Peróxido de Hidrogênio/química , Simulação de Acoplamento Molecular , Óxido Nítrico/química , Picratos/química , Pigmentação/efeitos dos fármacos
12.
Molecules ; 26(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064423

RESUMO

In the present study, we evaluated for the first time the photoprotective effect of fish bone bioactive peptides (FBBP) preparation isolated from silver carp (Hypophthalmichthys molitrix) discarded tissue using in vitro experimental models of skin cells exposed to ultraviolet B (UVB) irradiation and stressing agents. FBBP preparation was obtained by papain treatment of minced bones and centrifugal ultrafiltration, and the molecular weight (MW) distribution was characterized by size exclusion and reversed-phase high performance liquid chromatography (RP-HPLC). In vitro assessment of the effect of FBBP pretreatment in UVB-irradiated L929 fibroblasts and HaCaT keratinocytes revealed their cytoprotective activity. Their capacity to efficiently reduce reactive oxygen species (ROS) production and lipid peroxidation varied in a dose-dependent manner, and it was greater in fibroblasts. A decrease of proinflammatory cytokines secretion, in particular of tumor necrosis factor alpha (TNF-α), was found after FBBP pretreatment of THP-1-derived inflamed macrophages. Melanin production and tyrosinase activity investigated in UVB-irradiated Mel-Juso cells were lowered in direct relation to FBBP concentrations. FBBP fractions with high radical scavenging activity were separated by ion exchange chromatography, and two collagenic sequences were identified. All these results offer new scientific data on aquaculture fish bone-derived peptides confirming their ability to control the antioxidant, anti-inflammatory and pigmentation processes developed during UV irradiation of skin cells and recommend their use as valuable natural ingredients of photoprotective cosmeceutical products.


Assuntos
Osso e Ossos/efeitos dos fármacos , Inflamação/patologia , Peptídeos/farmacologia , Pigmentação , Pele/efeitos da radiação , Raios Ultravioleta , Animais , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Citoproteção/efeitos dos fármacos , Citoproteção/efeitos da radiação , Peixes , Células HaCaT/efeitos dos fármacos , Células HaCaT/efeitos da radiação , Humanos , Mediadores da Inflamação/metabolismo , Espaço Intracelular/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Malondialdeído/metabolismo , Melaninas/biossíntese , Camundongos , Peso Molecular , Oxirredução/efeitos dos fármacos , Oxirredução/efeitos da radiação , Peptídeos/isolamento & purificação , Pigmentação/efeitos dos fármacos , Pigmentação/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta , Células THP-1
13.
J Cell Mol Med ; 24(7): 4023-4035, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32096914

RESUMO

As a main part of pigmentation disorders, skin depigmentation diseases such as vitiligo and achromic naevus are very common and get more attention now. The pathogenesis of depigmentation includes melanocyte dysfunction and loss, which are possibly caused by heredity, autoimmunity and oxidative stress. Among them, oxidative stress plays a key role; however, few clinical treatments can deal with oxidative stress. As reported, Cistanche deserticola polysaccharide (CDP) is an effective antioxidant; based on that, we evaluated its role in melanocyte and further revealed the mechanisms. In this study, we found that CDP could promote melanogenesis in human epidermal melanocytes (HEMs) and mouse melanoma B16F10 cells, it also induced pigmentation in zebrafish. Furthermore, CDP could activate mitogen-activated protein kinase (MAPK) signal pathway, then up-regulated the expression of microphthalmia-associated transcription factor (MITF) and downstream genes TYR, TRP1, TRP2 and RAB27A. Otherwise, we found that CDP could attenuate H2 O2 -induced cytotoxicity and apoptosis in melanocytes. Further evidence revealed that CDP could enhance NRF2/HO-1 antioxidant pathway and scavenge intracellular ROS. In summary, CDP can promote melanogenesis and prevent melanocytes from oxidative stress injury, suggesting that CDP helps maintain the normal status of melanocytes. Thus, CDP may be a novel drug for the treatment of depigmentation diseases.


Assuntos
Cistanche/química , Heme Oxigenase-1/genética , Melaninas/genética , Proteínas de Membrana/genética , Fator 2 Relacionado a NF-E2/genética , Polissacarídeos/farmacologia , Animais , Humanos , Melaninas/antagonistas & inibidores , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/genética , Melanoma Experimental/patologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Pigmentação/efeitos dos fármacos , Pigmentação/genética , Transtornos da Pigmentação/tratamento farmacológico , Transtornos da Pigmentação/genética , Transtornos da Pigmentação/patologia , Polissacarídeos/química , Peixe-Zebra/genética
14.
J Cell Physiol ; 235(10): 6808-6816, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31989660

RESUMO

Alkaptonuria (AKU) is a rare disease correlated with deficiency of the enzyme homogentisate 1,2 dioxygenase, which causes homogentisic acid (HGA) accumulation. HGA is subjected to oxidation/polymerization reactions, leading to the production of a peculiar melanin-like pigmentation (ochronosis) after chronic inflammation, which is considered as a triggering event for the generation of oxidative stress. Clinical manifestations of AKU are urine darkening, sclera pigmentation, early severe osteoarthropathy, and cardiovascular and renal complication. Despite major clinical manifestations of AKU being observed in the bones and skeleton, the molecular and functional parameters are so far unknown in AKU. In the present study, we used human osteoblasts supplemented with HGA as a AKU cellular model. We observed marked oxidative stress, and for the first time, we were able to correlate HGA deposition with an impairment in the Wnt/ß-catenin signaling pathway, opening a range of possible therapeutic strategies for a disease still lacking a known cure.


Assuntos
Ácido Homogentísico/farmacologia , Osteoblastos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Alcaptonúria/metabolismo , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Células Cultivadas , Humanos , Inflamação/metabolismo , Melaninas/metabolismo , Ocronose/metabolismo , Osteoblastos/metabolismo , Oxirredução/efeitos dos fármacos , Pigmentação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
15.
Biochem Biophys Res Commun ; 523(4): 1034-1039, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-31973810

RESUMO

Dasatinib, a second-generation tyrosine kinase inhibitor, is indicated for the therapy of imatinib-resistant leukemia and also for the treatment of solid cancers. Here, we report a novel effect of dasatinib of inducing differentiation in normal human melanocytes. Treatment with dasatinib significantly increased the melanin content and tyrosinase activity through the up-regulation of MITF and tyrosinase expressions. Consistently, dasatinib had clear stimulatory action in the pigmentation of ex vivo cultured skin. The molecular mechanism underlying the melanogenic effect of dasatinib was associated with the ERK-dependent phosphorylation of CREB. The ERK inhibitor PD98059 not only inhibited the phosphorylation of CREB but also abrogated dasatinib-induced melanocyte differentiation. These results demonstrate for the first time the capacity of dasatinib to induce differentiation in normal human melanocytes depending on the activation of ERK-CREB-MITF-tyrosinase signaling cascades.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dasatinibe/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Melaninas/biossíntese , Melanócitos/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais , Adolescente , Adulto , Humanos , Pigmentação/efeitos dos fármacos , Pele/metabolismo
16.
Arch Toxicol ; 94(7): 2413-2421, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32388820

RESUMO

Previous rat toxicity studies of alpha-glycosyl isoquercitrin (AGIQ), a water-soluble flavonol glycoside derived from rutin, revealed systemic yellow bone discoloration. This investigative study was conducted to determine the AGIQ metabolite(s) responsible for the discoloration. Female Sprague-Dawley rats were administered dietary AGIQ at doses of 0%, 1.5%, 3.0%, or 5.0% (0, 1735.0, 3480.8, and 5873.7 mg/kg/day, respectively) for 14 days, followed by a 14- or 28-day recovery period. Measurements of quercetin in urine and quercetin, quercetin 3-O-glucuronide, kaempferol, and 3-o-methylquercetin metabolites of AGIQ in bone (femur), white and brown fat, and cerebrum samples were conducted following the exposure period and each recovery period. Gross examination of the femur revealed yellow discoloration that increased in intensity with dose and was still present in a dose-related manner following both recovery periods. Quercetin, at levels correlating with AGIQ dose, was measured in the urine following the 14-day exposure period and, at lower concentrations, 14 or 28 days following cessation of AGIQ exposure. All four metabolites were present in a dose-dependent manner in the femur following 14 days of dietary exposure; only quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were present during the recovery periods. Quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were detected in white fat (along with kaempferol), brown fat (excluding quercetin due to analytical interference), and cerebrum samples, indicating systemic availability of the metabolites. Collectively, these data implicate quercetin, quercetin 3-O-glucuronide, or 3-o-methylquercetin (or a combination thereof) as the most likely metabolite of AGIQ causing the yellow discoloration of bone in rats administered dietary AGIQ.


Assuntos
Fêmur/efeitos dos fármacos , Transtornos da Pigmentação/induzido quimicamente , Pigmentação/efeitos dos fármacos , Quercetina/toxicidade , Animais , Biotransformação , Feminino , Fêmur/patologia , Transtornos da Pigmentação/patologia , Quercetina/análogos & derivados , Quercetina/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo
17.
Int J Mol Sci ; 21(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31906440

RESUMO

Fisetin is found in many fruits and plants such as grapes and onions, and exerts anti-inflammatory, anti-proliferative, and anticancer activity. However, whether fisetin regulates melanogenesis has been rarely studied. Therefore, we evaluated the effects of fisetin on melanogenesis in B16F10 melanoma cell and zebrafish larvae. The current study revealed that fisetin slightly suppressed in vitro mushroom tyrosinase activity; however, molecular docking data showed that fisetin did not directly bind to mushroom tyrosinase. Unexpectedly, fisetin significantly increased intracellular and extracellular melanin production in B16F10 melanoma cells regardless of the presence or absence of α-melanocyte stimulating hormone (α-MSH). We also found that the expression of melanogenesis-related genes such as tyrosinase and microphthalmia-associated transcription factor (MITF), were highly increased 48 h after fisetin treatment. Pigmentation of zebrafish larvae by fisetin treatment also increased at the concentrations up to 200 µM and then slightly decreased at 400 µM, with no alteration in the heart rates. Molecular docking data also revealed that fisetin binds to glycogen synthase kinase-3ß (GSK-3ß). Therefore, we evaluated whether fisetin negatively regulated GSK-3ß, which subsequently activates ß-catenin, resulting in melanogenesis. As expected, fisetin increased the expression of ß-catenin, which was subsequently translocated into the nucleus. In the functional assay, FH535, a Wnt/ß-catenin inhibitor, significantly inhibited fisetin-mediated melanogenesis in zebrafish larvae. Our data suggested that fisetin inhibits GSK-3ß, which activates ß-catenin, resulting in melanogenesis through the revitalization of MITF and tyrosinase.


Assuntos
Flavonoides/farmacologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Melaninas/biossíntese , beta Catenina/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/química , Flavonoides/toxicidade , Flavonóis , Glicogênio Sintase Quinase 3 beta/química , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Melanoma Experimental , Camundongos , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Pigmentação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , alfa-MSH/farmacologia , beta Catenina/antagonistas & inibidores , beta Catenina/genética
18.
Molecules ; 25(7)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32244349

RESUMO

Ceramides have several well-known biological properties, including anti-pigmentation and anti-melanogenesis, which make them applicable for use in skincare products in cosmetics. However, the efficacy of ceramides is still limited. Dermal or transdermal drug delivery systems can enhance the anti-pigmentation properties of ceramides, although there is currently no systemic evaluation method for the efficacy of these systems. Here we prepared several types of lecithin-based emulsion of maize-derived glucosylceramide, determining PC70-ceramide (phosphatidylcholine-base) to be the safest and most effective anti-pigmentation agent using zebrafish larvae. We also demonstrated the efficacy of PC70 as a drug delivery system by showing that PC70-Nile Red (red fluorescence) promoted Nile Red accumulation in the larval bodies. In addition, PC70-ceramide suppressed melanin in mouse B16 melanoma cells compared to ceramide alone. In conclusion, we developed a lecithin-based dermal delivery method for ceramide using zebrafish larvae with implications for human clinical use.


Assuntos
Ceramidas/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lecitinas/química , Pigmentação/efeitos dos fármacos , Zea mays/química , Animais , Ceramidas/química , Melanoma Experimental , Camundongos , Pigmentação da Pele/efeitos dos fármacos , Peixe-Zebra
19.
Int J Cosmet Sci ; 42(2): 127-135, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31799709

RESUMO

OBJECTIVE: The objective is to develop a natural cosmetic ingredient from Eryngium maritimum regarding the high interest of consumer in these ingredients for cosmetic use. METHODS: Five eco-friendly techniques of extraction were applied to Eryngium maritimum aerial parts among conventional reflux extraction (with green solvent) and alternative techniques (supercritical fluid extraction (SFE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE) and ultrasound combined with microwave extraction (UAE + MAE)). Several criteria were evaluated to allow the optimal choice for an industrialized ingredient: yield of extraction, chemical composition and biological activities such as antimicrobial, antioxidant, anti-collagenase and anti-tyrosinase activities. The extracts were analysed by liquid chromatography mass spectrometry (LC-HRMS), and the hierarchical Pearson classification (HCA) allowed to highlight the group of metabolites preferably extracted depending on the technique of extraction used. RESULTS: The biological results highlight that SFE and 80% ethanol reflux extracts have the best responses to biological activities such as antimicrobial, depigmenting and antioxidant activities, followed by water reflux extraction. Their activities might be due to the presence of different groups of metabolites favourably extracted by these techniques. CONCLUSION: Among these extractions, water reflux extraction provided the optimal results considering the compromise between extraction yield and biological activities for the development of a cosmetic ingredient.


OBJECTIF: L'objectif est d'évaluer différentes méthodes d'extraction permettant l'obtention d'un ingrédient cosmétique naturel, à partir d'Eryngium maritimum, efficace biologiquement, et respectant les principes du développement durable et de la beauté éthique et responsable. MÉTHODES: Cinq techniques d'extraction respectueuses de l'environnement ont été appliquées à des parties aériennes d'Eryngium maritimum tels que le reflux conventionnel (avec des solvants agrosourcés) et des techniques alternatives (extraction au fluide supercritique (SFE), extraction assistée par micro-ondes (MAE), extraction assistée par ultrasons (UAE) et ultrasons combinés aux micro-ondes (UAE + MAE)). Plusieurs critères ont été évalués pour permettre le choix optimal d'un ingrédient cosmétique efficace, naturel et industrialisable : rendement d'extraction, composition chimique (sureté) et efficacités biologiques (antibactérien, antioxydant, anti-âge et dépigmentant). Les extraits ont été analysés par chromatographie liquide spectrométrie de masse (LC-HRMS), et la classification par hiérarchie de Pearson (HCA) a permis de mettre relier les groupes de métabolites extraits de préférence par technique d'extraction testée. RÉSULTATS: Les résultats biologiques mettent en évidence que les extractions par SFE et à reflux par éthanol 80% permettaient les meilleures réponses (les plus importantes) pour des activités antimicrobiennes, éclaircissantes et antioxydantes, devant l'extraction à reflux par l'eau. Leurs activités pourraient être dues à la présence préférentielle de certains groupes de métabolites extraits plus favorablement par ces techniques. CONCLUSION: Parmi les extractions testées, l'extraction par reflux à l'eau (procédé respectueux de l'environnement) d'Eryngium maritimum, fournit le meilleur compromis en termes d'efficacités biologiques plurielles, de rendement d'extraction et de productivité/consommation énergétique, pour le développement d'un ingrédient cosmétique 'ecofriendly'.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Cosméticos , Eryngium/química , Pigmentação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Cromatografia com Fluido Supercrítico/métodos
20.
Trop Anim Health Prod ; 52(4): 1549-1552, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31820307

RESUMO

A study was conducted to investigate the effect of feeding complete feed as total mixed ration (TMR) with two levels of zeolite on copper (Cu), iron (Fe), and zinc (Zn) status and rumen color of growing Naemi lambs. Twenty-four growing lambs (25 ± 2.1 kg body weight) were individually kept in separate pens with ad libitum feed and water. The lambs were randomly distributed to three treatments as follow: control, TMR diet only; T1, TMR with 1% zeolite daily; T2, TMR with 2% zeolite daily. The trial was lasted for 56 days. Four lambs from each treatment were slaughtered and tissue (liver, kidney, meat, and rumen tissues) and rumen fluid samples were collected. A significantly (P < 0.05) high concentration of Fe was found in T2 in blood and rumen fluid samples of lambs supplemented with zeolite. In the meat tissue, significantly (P < 0.05) high concentration of Zn was found in the treatment groups compared with the control, while Cu concentration decreased significantly (P < 0.05) in T1. In addition, rumen dark color was reduced in the zeolite-supplemented groups. We concluded that supplementation of zeolite at the rate of 1 or 2% did not appear to have any adverse effects on the blood profile of trace elements. Moreover, under these two levels of zeolite, discoloration of the rumen was significantly reduced in response to the supplementation of zeolite.


Assuntos
Ração Animal/análise , Suplementos Nutricionais , Pigmentação/efeitos dos fármacos , Ovinos/crescimento & desenvolvimento , Oligoelementos/metabolismo , Zeolitas/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Peso Corporal/efeitos dos fármacos , Cobre , Dieta/veterinária , Ferro , Rúmen , Zinco
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