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1.
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 , 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
2.
Mar Drugs ; 19(3)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802989

RESUMO

The liver is vulnerable to oxidative stress-induced damage, which leads to many diseases, including alcoholic liver disease (ALD). Liver disease endanger people's health, and the incidence of ALD is increasing; therefore, prevention is very important. 7-phloro-eckol (7PE) is a seaweed polyphenol, which was isolated from Ecklonia cava in a previous study. In this study, the antioxidative stress effect of 7PE on HepG2/CYP2E1 cells was evaluated by alcohol-induced cytotoxicity, DNA damage, and expression of related inflammation and apoptosis proteins. The results showed that 7PE caused alcohol-induced cytotoxicity to abate, reduced the amount of reactive oxygen species (ROS) and nitric oxide (NO), and effectively inhibited DNA damage in HepG2/CYP2E1 cells. Additionally, the expression levels of glutathione (GSH), superoxide dismutase (SOD), B cell lymphoma 2 (Bcl-2), and Akt increased, while γ-glutamyltransferase (GGT), Bcl-2 related x (Bax), cleaved caspase-3, cleaved caspase-9, nuclear factor-κB (NF-κB), and JNK decreased. Finally, molecular docking proved that 7PE could bind to BCL-2 and GSH protein. These results indicate that 7PE can alleviate the alcohol-induced oxidative stress injury of HepG2 cells and that 7PE may have a potential application prospect in the future development of antioxidants.


Assuntos
Antioxidantes/farmacologia , Citocromo P-450 CYP2E1/metabolismo , Dioxinas/farmacologia , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Alga Marinha/metabolismo , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Dioxinas/isolamento & purificação , Etanol/toxicidade , Células Hep G2 , Hepatócitos/enzimologia , Humanos , Mediadores da Inflamação/metabolismo , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
3.
Mar Drugs ; 18(9)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957728

RESUMO

Diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae (IO) showed potential whitening effects against UV-B radiation. However, the components of IO as well as their molecular mechanism against α-melanocyte-stimulating hormone (α-MSH) have not yet been investigated. Thus, this study aimed to investigate the inhibitory effects of Ishophloroglucin A (IPA), a phlorotannin isolated from brown algae IO, and its crude extract (IOE), in melanogenesis in vivo in an α-MSH-induced zebrafish model and in B16F10 melanoma cells in vitro. Molecular docking studies of the phlorotannins were carried out to determine their inhibitory effects and to elucidate their mode of interaction with tyrosinase, a glycoprotein related to melanogenesis. In addition, morphological changes and melanin content decreased in the α-MSH-induced zebrafish model after IPA and IOE treatment. Furthermore, Western blotting results revealed that IPA upregulated the extracellular related protein expression in α-MSH-stimulated B16F10 cells. Hence, these results suggest that IPA isolated from IOE has a potential for use in the pharmaceutical and cosmetic industries.


Assuntos
Benzofuranos/farmacologia , Dioxinas/farmacologia , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Preparações Clareadoras de Pele/farmacologia , alfa-MSH/farmacologia , Animais , Benzofuranos/isolamento & purificação , Dioxinas/isolamento & purificação , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Fosforilação , Preparações Clareadoras de Pele/isolamento & purificação , Peixe-Zebra , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Nutrients ; 12(5)2020 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-32397556

RESUMO

Eckol, a precursor compound belonging to the dibenzo-1,4-dioxin class of phlorotannins, is a phloroglucinol derivative that exerts various activities. In the present study, we investigated the antiallergic effects of eckol isolated from the marine brown algae, Ecklonia cava using immunoglobulin E (IgE)/bovine serum albumin (BSA)-stimulated mouse bone marrow-derived cultured mast cells (BMCMC) and a mouse model of anaphylaxis. Eckol inhibited IgE/BSA-induced BMCMC degranulation by reducing ß-hexosaminidase release. A flow cytometric analysis revealed that eckol decreases FcεRI expression on cell surface and IgE binding to the FcεRI in BMCMC. Moreover, eckol suppressed the production of the cytokines, interleukin (IL)-4, IL-5, IL-6, and IL-13 and the chemokine, thymus activation-regulated chemokine (TARC) by downregulating, IκB-α degradation and NF-κB nuclear translocation. Furthermore, it attenuated the passive cutaneous anaphylactic reaction induced by IgE/BSA-stimulation in the ear of BALB/c mice. These results suggest that eckol is a potential therapeutic candidate for the prevention and treatment of allergic disorders.


Assuntos
Anafilaxia/tratamento farmacológico , Antialérgicos , Dioxinas/farmacologia , Dioxinas/uso terapêutico , Imunoglobulina E/imunologia , Mastócitos/imunologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Anafilaxia Cutânea Passiva/imunologia , Fitoterapia , Anafilaxia/imunologia , Animais , Células Cultivadas , Dioxinas/isolamento & purificação , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
5.
J Chromatogr A ; 1614: 460701, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31866133

RESUMO

Polychlorinated dibenzo-p-dioxins and furans offer a complex separation challenge due to their chemical similarity and 5020 possible congeners, including the Br/Cl congeners. Not only are these compounds difficult to separate, but they are also difficult to identify. Expensive reference materials are needed for conventional "dioxin analysis", usually requiring 13C labeled and native compounds. A retention index database offers a potential solution to lower the difficulty and cost to identify dioxins. This study describes the use of Kovats and Lee retention indices for the identification of chlorinated dioxins and furans as well as their brominated and mixed chloro/bromo counterparts. Eight columns were characterized with all 136 tetra through octa substituted chlorinated dioxins and furans as well as 32 brominated and mixed chloro/bromo congeners. Columns were then compared to identify which stationary phases provided the best resolution for critical congeners, like the 2,3,7,8 substituted compounds. Column phase selectivity was also investigated to identify best commercially-available column pairings for confirmatory analyses and GC × GC separations. The Rtx-Dioxin2 and Rxi-17SilMS showed unique selectivity for dioxins and furans and could be used as confirmatory columns or as a powerful GC × GC column set.


Assuntos
Cromatografia Gasosa/métodos , Dioxinas/análise , Dibenzofuranos Policlorados/análise , Dioxinas/isolamento & purificação , Dibenzodioxinas Policloradas/análise
6.
Environ Sci Process Impacts ; 21(10): 1754-1763, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31532404

RESUMO

An integrated in vitro and in silico approach was applied to evaluate the potency of hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and spongiadioxins (OH-PBDDs) isolated from Dysidea sponges on the activity of the recombinant α-d-galactosidase of the GH36 family. It was revealed for the first time that all compounds rapidly and apparently irreversibly inhibited the bacterial α-d-galactosidase. The structure-activity relationship study in the series of OH-PBDEs showed that the presence of an additional hydroxyl group in 5 significantly enhanced the potency (IC50 4.26 µM); the increase of bromination in compounds from 1 to 3 increased their potency (IC50 41.8, 36.0, and 16.0 µM, respectively); the presence of a methoxy group decreased the potency (4, IC50 60.5 µM). Spongiadioxins 6, 7, and 8 (IC50 16.6, 33.1, and 28.6 µM, respectively) exhibited inhibitory action comparable to that of monohydroxylated diphenyl ethers 1-3. Docking analysis revealed that all compounds bind in a pocket close to the catalytic amino acid residues. Molecular docking detected significant compound-enzyme interactions in the binding sites of α-d-galactosidase. Superimposition of the enzyme-substrate and the enzyme-inhibitor complexes showed that their binding sites overlap.


Assuntos
Dioxinas/química , Dysidea/química , Éteres Difenil Halogenados/química , alfa-Galactosidase/química , Animais , Dioxinas/isolamento & purificação , Éteres Difenil Halogenados/isolamento & purificação , Halogenação , Modelos Moleculares , Simulação de Acoplamento Molecular , Domínios Proteicos , alfa-Galactosidase/antagonistas & inibidores
7.
N Biotechnol ; 48: 83-89, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30098416

RESUMO

Bioactive compounds such as karrikinolide (KAR1 from smoke) and eckol (from the seaweed Ecklonia maxima) show promising effects on several important crop plants. These plant growth-stimulating organic biomolecules, along with crude extracts (smoke-water and Kelpak® product prepared from Ecklonia maxima), were tested on spinach plants. Eckol sprayed at 10-6 M significantly increased all the growth and biochemical parameters examined compared to control spinach plants. All tested plant growth biostimulants significantly increased total chlorophyll, carotenoids and protein content of spinach leaves. The cytokinin profile of spinach plants was also determined. Cis-zeatin, dihydrozeatin and isopentenyladenine types of cytokinins were promoted by both smoke- and seaweed-based biostimulants. In comparison to the control plants, the level of free sinapic acid was greater in all spinach plants treated with these biostimulants. The application of these biostimulants can help spinach crop by improving growth, yield and nutritional quality; moreover, they are organic and cost-effective.


Assuntos
/química , Reguladores de Crescimento de Plantas/isolamento & purificação , Reguladores de Crescimento de Plantas/farmacologia , Alga Marinha/química , Fumaça/análise , Spinacia oleracea/efeitos dos fármacos , Spinacia oleracea/crescimento & desenvolvimento , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Citocininas/metabolismo , Dioxinas/isolamento & purificação , Dioxinas/farmacologia , Furanos/isolamento & purificação , Furanos/farmacologia , Hidroxibenzoatos/metabolismo , Piranos/isolamento & purificação , Piranos/farmacologia , Spinacia oleracea/metabolismo
8.
Mar Drugs ; 16(11)2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30423960

RESUMO

Ecklonia cava (E. cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in an ethanoic extract of E. cava. These four major compounds were isolated and their effects were examined on monocyte-associated vascular inflammation and dysfunctions. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) significantly inhibited monocyte migration in vitro by reducing levels of inflammatory macrophage differentiation and of its related molecular factors. In addition, PPB protected against monocyte-associated endothelial cell death by increasing the phosphorylations of PI3K-AKT and AMPK, decreasing caspase levels, and reducing monocyte-associated vascular smooth muscle cell proliferation and migration by decreasing the phosphorylations of ERK and AKT. The results of this study show that four compounds were effective for reduction of monocyte-associated vascular inflammation and dysfunctions, but PPB might be more useful for the treatment of vascular dysfunction in diseases associated with poor circulation.


Assuntos
Anti-Inflamatórios/farmacologia , Dioxinas/farmacologia , Monócitos/efeitos dos fármacos , Floroglucinol/farmacologia , Extratos Vegetais/farmacologia , Pirogalol/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dioxinas/química , Dioxinas/isolamento & purificação , Dioxinas/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Camundongos , Monócitos/metabolismo , Monócitos/fisiologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/fisiologia , Floroglucinol/química , Floroglucinol/isolamento & purificação , Floroglucinol/uso terapêutico , Extratos Vegetais/química , Pirogalol/química , Pirogalol/isolamento & purificação , Pirogalol/uso terapêutico , Doenças Vasculares/tratamento farmacológico
9.
J Environ Manage ; 223: 797-806, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29986327

RESUMO

Rapid urbanization and industrialization of anthropogenic activities have exerted immense pressure on the environment. Polyhalogenated organic compounds, especially dioxins and furans are regarded as ubiquitously persistent environmental pollutants in the ecosystem. The recalcitrant nature of dioxins and furans induce toxicity in both humans and wildlife. Dioxins and furans are generated by defective technological chemical processes that occur during the manufacture of herbicides and pesticides, use of fertilizers, bleaching of paper and wood pulp and incomplete combustion process. However, incineration and incomplete combustion of solid waste are the main cause for the discharge of dioxins and furans to the environment. During incineration and incomplete combustion, noxious flue gas and ashes are released into the atmosphere and contaminate the soil and water systems; thereby affecting the ecology. According to World Health Organization fact sheet 2016, more than 90% of human exposure to dioxins is through the food chain, especially from dairy products, seafood and meat. These pollutants are mutagenic, carcinogenic, immunotoxic and teratogenic for lower and higher forms of life i.e. microorganisms to humans. This review describes the sources of dioxins and furans pollution, hazardous effects on the ecosystem and recent techniques to minimize and treat dioxins and furans contaminants in the environment. This paper also previews the significance of conventional and latest remediation techniques prevailing around the globe for treating dioxins and furans entry into the ecosystem.


Assuntos
Dioxinas/isolamento & purificação , Poluição Ambiental/prevenção & controle , Furanos/isolamento & purificação , Dioxinas/química , Furanos/química , Humanos , Incineração , Praguicidas
10.
Mar Drugs ; 16(1)2018 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-29300311

RESUMO

UV light, especially UVB, is known as a trigger of allergic reaction, leading to mast cell degranulation and histamine release. In this study, phlorotannin Fucofuroeckol-A (F-A) derived from brown algal Ecklonia stolonifera Okamura was evaluated for its protective capability against UVB-induced allergic reaction in RBL-2H3 mast cells. It was revealed that F-A significantly suppress mast cell degranulation via decreasing histamine release as well as intracellular Ca2+ elevation at the concentration of 50 µM. Moreover, the inhibitory effect of F-A on IL-1ß and TNF-α productions was also evidenced. Notably, the protective activity of F-A against mast cell degranulation was found due to scavenging ROS production. Accordingly, F-A from brown algal E. stolonifera was suggested to be promising candidate for its protective capability against UVB-induced allergic reaction.


Assuntos
Antialérgicos/farmacologia , Benzofuranos/farmacologia , Degranulação Celular/efeitos dos fármacos , Dioxinas/farmacologia , Mastócitos/efeitos dos fármacos , /metabolismo , Animais , Antialérgicos/química , Antialérgicos/isolamento & purificação , Benzofuranos/química , Benzofuranos/isolamento & purificação , Cálcio/metabolismo , Degranulação Celular/efeitos da radiação , Linhagem Celular Tumoral , Dioxinas/química , Dioxinas/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Histamina/metabolismo , Interleucina-1beta/antagonistas & inibidores , Mastócitos/metabolismo , Mastócitos/efeitos da radiação , Ratos , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Raios Ultravioleta/efeitos adversos
11.
J Food Prot ; 80(8): 1228-1238, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28686496

RESUMO

Polychlorinated biphenyls (PCBs; sum of 36 congeners) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs; sum of 17 2,3,7,8-substituted congeners) were measured in 93 composite samples prepared from individual lake trout (Salvelinus namaycush) and whitefish (Coregonus clupeaformis) samples collected from Lake Erie, Lake Huron, and Lake Superior. All samples had detectable concentrations of PCBs and PCDD/Fs; maximum PCB concentrations in both trout (750 ng g-1 whole weight [ww]) and whitefish (210 ng g-1 ww) were found in composites from fish collected from Lake Huron. The maximum toxic equivalent concentration was found in a lake trout composite sample from Lake Huron (53 pg g-1 ww). PCB and PCDD/F congener profiles were comparable to patterns observed in fishes collected from other regions of Canada, although concentrations were above those found in other regions. A positive correlation was found between PCB concentrations determined using the historical Aroclor equivalency method and those determined using the sum of the congeners measured (r2 = 0.871; Spearman correlation r = 0.917) or using the six indicator PCB congeners (28, 52, 101, 138, 153, and 180; r2 = 0.850; Spearman correlation r = 0.935). PCBs were the dominant contributor to the overall toxic equivalent concentrations in the fish composite samples tested. These findings provide insight into PCB and PCDD/F concentrations in two commercially important fish species over a discrete time period.


Assuntos
Dioxinas/isolamento & purificação , Contaminação de Alimentos/análise , Bifenilos Policlorados/isolamento & purificação , Salmonidae/metabolismo , Truta/metabolismo , Animais , Canadá , Pesqueiros , Furanos , Lagos
12.
Arch Pharm Res ; 40(4): 480-491, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28251489

RESUMO

Eckol and dieckol are important phlorotannins found in edible brown algae including Eisenia bicyclis, Ecklonia stolonifera, and others. Inhibition of monoamine oxidase (MAO) play an important role in the early management of Parkinson's disease (PD). The aim of this study was to determine the effectiveness of eckol and dieckol isolated from the methanolic extract of E. bicyclis against PD by the inhibition of human MAO-A and MAO-B (hMAO-A and hMAO-B). A sensitive enzyme-based chemiluminescent assay and kinetics methods were used to investigate enzyme inhibition and mode of inhibition. A molecular docking simulation was performed to clarify the binding characteristics of eckol and dieckol to hMAO-A and hMAO-B. The results suggested that methanolic extract of E. bicyclis and its isolated phlorotannins, eckol and dieckol, have potent inhibitory activity against hMAO-A and hMAO-B. The enzyme-based kinetics results demonstrated eckol mixed and non-competitive inhibition of hMAO-A and hMAO-B, respectively, while dieckol non-competitively inhibited both hMAOs. Molecular docking simulation predicted that eckol and dieckol exhibit higher binding affinity towards hMAO-A and hMAO-B through hydrogen bonding and hydrophobic interactions. These findings implicate eckol and dieckol as inhibitors of hMAOs that might be of potential value in the management of PD.


Assuntos
Benzofuranos/farmacologia , Dioxinas/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , /química , Benzofuranos/química , Benzofuranos/isolamento & purificação , Dioxinas/química , Dioxinas/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/isolamento & purificação , Relação Estrutura-Atividade
13.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1041-1042: 70-76, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28012381

RESUMO

We have utilized an automated acid hydrolysis technology, followed by an abbreviated Soxhlet extraction technique to obtain fat from whole milk for the determination of persistent organic pollutants, namely polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls. The process simply involves (1) pouring the liquid milk into the hydrolysis beaker with reagents and standards, (2) drying the obtained fat on a filter paper and (3) obtaining pure fat via the modified Soxhlet extraction using 100mL of hexane per sample. This technique is in contrast to traditional manually intense liquid-liquid extractions and avoids the preparatory step of freeze-drying the samples for pressurized liquid extractions. Along with these extraction improvements, analytical results closely agree between the methods, thus no quality has been compromised. The native spike (n=12) and internal standard (n=24) precision and accuracy results are within EPA Methods 1613 and 1668 limits. While the median (n=6) Toxic Equivalency Quotient (TEQ) for polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans and the concentration of the marker polychlorinated biphenyls show a percent difference of 1% and 12%, respectively, compared to 315 previously analyzed milk samples at the same laboratory using liquid-liquid extraction. During our feasibility studies, both egg and fish tissue show substantial promise using this technique as well.


Assuntos
Dioxinas/análise , Poluentes Ambientais/análise , Gorduras/isolamento & purificação , Extração Líquido-Líquido/métodos , Leite/química , Bifenilos Policlorados/análise , Animais , Automação , Dioxinas/química , Dioxinas/isolamento & purificação , Poluentes Ambientais/química , Poluentes Ambientais/isolamento & purificação , Gorduras/química , Hidrólise , Bifenilos Policlorados/química , Bifenilos Policlorados/isolamento & purificação , Reprodutibilidade dos Testes
14.
Planta Med ; 83(6): 565-573, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27760442

RESUMO

Fungal endophytes offer diverse and unique secondary metabolites, making these organisms potential sources of promising drug leads. The application of high-resolution-liquid chromatography mass spectrometry and nuclear magnetic resonance-based metabolomics to fungal endophytes is practical in terms of dereplication studies and the mining of bioactive compounds. In this paper, we report the application of metabolomics in parallel with anti-trypanosomal assays to determine the ideal conditions for the medium-scale fermentation of the endophyte Lasiodiplodia theobromae. The 1H NMR comparison between the active versus inactive fractions identified several unique chemical fingerprints belonging to the active fractions. Furthermore, by integrating high-resolution-liquid chromatography mass spectrometry data with multivariate data analysis, such as orthogonal partial least squares-discriminant analysis (OPLS-DA) and the bioactivity results of the fractions of L. theobromae, the anti-trypanosomal agents were easily discerned. With available databases such as Antibase and Dictionary of Natural Products coupled to MZmine through in-house algorithms optimized in our laboratory, the predicted metabolites were readily identified prior to isolation. Fractionation was performed on the active fractions and three known compounds were isolated, namely, cladospirone B, desmethyl-lasiodiplodin, and R-(-)-mellein. Cladospirone B and desmethyl-lasiodiplodin were among the predicted compounds generated by the OPLS-DA S-plot, and these compounds exhibited good activity against Trypanosoma brucei brucei with minimum inhibitory concentrations of 17.8 µM and 22.5 µM, respectively.


Assuntos
Ascomicetos/química , Dioxinas/isolamento & purificação , Tripanossomicidas/isolamento & purificação , Trypanosoma brucei brucei/efeitos dos fármacos , Zearalenona/análogos & derivados , Algoritmos , Ascomicetos/metabolismo , Produtos Biológicos , Cromatografia Líquida , Dioxinas/química , Dioxinas/farmacologia , Endófitos/química , Endófitos/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Metabolômica/métodos , Testes de Sensibilidade Microbiana , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Zearalenona/química , Zearalenona/isolamento & purificação , Zearalenona/farmacologia
15.
Nat Prod Rep ; 33(6): 801-11, 2016 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-26867808

RESUMO

Covering: up to 2016.When looking for dibenzofuran in the biochemical databases, most papers and reviews deal with pollutants and polychlorinated dibenzofurans like dioxins. But dibenzofurans are also biosynthetized by a wide diversity of organisms in nature. Even if dibenzofurans from natural sources represent a small class of secondary metabolites, compared to flavonoids, xanthones or terpenoids, they are often endowed with interesting biological properties which have been recently described. This review provides an update on papers describing dibenzofurans from lichens, ascomycetes and cultured mycobionts. Other sources, such as basidiomycetes, myxomycetes or plants produce sporadically interesting dibenzofurans in terms of structures and activities.


Assuntos
Ascomicetos/química , Dibenzofuranos/isolamento & purificação , Líquens/química , Dibenzofuranos/química , Dibenzofuranos/farmacologia , Dioxinas/química , Dioxinas/isolamento & purificação , Dioxinas/farmacologia , Estrutura Molecular , Mixomicetos/química
16.
J Nat Prod ; 78(12): 2983-93, 2015 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-26595875

RESUMO

The antiproliferative and antitumor activities of americanin A (1), a neolignan isolated from the seeds of Phytolacca americana, were investigated in human colon cancer cells. Compound 1 inhibited the proliferation of HCT116 human colon cancer cells both in vitro and in vivo. The induction of G2/M cell-cycle arrest by 1 was concomitant with regulation of the ataxia telangiectasia-mutated/ATM and Rad3-related (ATM/ATR) signaling pathway. Treatment with 1 activated ATM and ATR, initiating the subsequent signal transduction cascades that include checkpoint kinase 1 (Chk1), checkpoint kinase 2 (Chk2), and tumor suppressor p53. Another line of evidence underlined the significance of 1 in regulation of the S phase kinase-associated protein 2 (Skp2)-p27 axis. Compound 1 targeted selectively Skp2 for degradation and thereby stabilized p27. Therefore, compound 1 suppressed the activity of cyclin B1 and its partner cell division cycle 2 (cdc2) to prevent entry into mitosis. Furthermore, prolonged treatment with 1 induced apoptosis by producing excessive reactive oxygen species. The intraperitoneal administration of 1 inhibited the growth of HCT116 tumor xenografts in nude mice without any overt toxicity. Modulation of the ATM/ATR signaling pathway and the Skp2-p27 axis might be plausible mechanisms of action for the antiproliferative and antitumor activities of 1 in human colon cancer cells.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Dioxinas/isolamento & purificação , Dioxinas/farmacologia , Phytolacca americana/química , Animais , Antineoplásicos Fitogênicos/química , Apoptose , Proteína Quinase CDC2/metabolismo , Quinase 1 do Ponto de Checagem , Quinase do Ponto de Checagem 2/metabolismo , Neoplasias do Colo , Dioxinas/química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Estrutura Molecular , Proteínas Quinases/metabolismo , Sementes/química , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo
17.
PLoS One ; 10(10): e0138805, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26466159

RESUMO

Hydroxylated polybrominated diphenyl ethers (OH-BDEs) are a new class of contaminants of emerging concern, but the relative roles of natural and anthropogenic sources remain uncertain. Polybrominated diphenyl ethers (PBDEs) are used as brominated flame retardants, and they are a potential source of OH-BDEs via oxidative transformations. OH-BDEs are also natural products in marine systems. In this study, OH-BDEs were measured in water and sediment of freshwater and coastal systems along with the anthropogenic wastewater-marker compound triclosan and its photoproduct dioxin, 2,8-dichlorodibenzo-p-dioxin. The 6-OH-BDE 47 congener and its brominated dioxin (1,3,7-tribromodibenzo-p-dioxin) photoproduct were the only OH-BDE and brominated dioxin detected in surface sediments from San Francisco Bay, the anthropogenically impacted coastal site, where levels increased along a north-south gradient. Triclosan, 6-OH-BDE 47, 6-OH-BDE 90, 6-OH-BDE 99, and (only once) 6'-OH-BDE 100 were detected in two sediment cores from San Francisco Bay. The occurrence of 6-OH-BDE 47 and 1,3,7-tribromodibenzo-p-dioxin sediments in Point Reyes National Seashore, a marine system with limited anthropogenic impact, was generally lower than in San Francisco Bay surface sediments. OH-BDEs were not detected in freshwater lakes. The spatial and temporal trends of triclosan, 2,8-dichlorodibenzo-p-dioxin, OH-BDEs, and brominated dioxins observed in this study suggest that the dominant source of OH-BDEs in these systems is likely natural production, but their occurrence may be enhanced in San Francisco Bay by anthropogenic activities.


Assuntos
Poluição Ambiental/análise , Água Doce/química , Sedimentos Geológicos/química , Éteres Difenil Halogenados/isolamento & purificação , Água do Mar/química , Poluentes Químicos da Água/isolamento & purificação , Cromatografia Líquida , Dioxinas/isolamento & purificação , Monitoramento Ambiental , Retardadores de Chama/isolamento & purificação , Humanos , Bifenil Polibromatos/isolamento & purificação , São Francisco , Espectrometria de Massas em Tandem , Triclosan/isolamento & purificação
18.
Int Immunopharmacol ; 28(2): 1068-75, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26341413

RESUMO

Microglial activation has been implicated in many neurological disorders for its inflammatory and neurotrophic effects. In this study, we investigated the effects of phlorofucofuroeckol B (PFF-B) isolated from Ecklonia stolonifera, on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated microglia. PFF-B decreased secretion of pro-inflammatory cytokines including tumor necrosis factor α, interleukin (IL)-1ß, and IL-6 and the expression of pro-inflammatory proteins such as cyclooxygenase-2 and inducible nitric oxide synthase in LPS-stimulated BV-2 cells. Profoundly, PFF-B inhibited activation of nuclear factor kappaB (NF-κB) by preventing the degradation of inhibitor κB-α (IκB-α), which led to prevent the nuclear translocation of p65 NF-κB subunit. Moreover, PFF-B inhibited the phosphorylation of Akt, ERK, and JNK. These results indicate that the anti-inflammatory effect of PFF-B on LPS-stimulated microglial cells is mainly regulated by the inhibition of IκB-α/NF-κB and Akt/ERK/JNK pathways. Our study suggests that PFF-B can be considered as a therapeutic agent against neuroinflammation by inhibiting microglial activation.


Assuntos
Anti-Inflamatórios/farmacologia , Benzofuranos/farmacologia , Dioxinas/farmacologia , Imunossupressores/farmacologia , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Animais , Benzofuranos/isolamento & purificação , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dioxinas/isolamento & purificação , Regulação para Baixo/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , MAP Quinase Quinase 4/metabolismo , Camundongos , Microglia/citologia , Microglia/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Proteína Oncogênica v-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos
19.
Environ Sci Pollut Res Int ; 22(22): 17691-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26154037

RESUMO

In this study, the removal efficiency of 136 tetra- to octa-chlorinated dibenzo-p-dioxin (CDD)/furan (F) congeners from a nitrogen + oxygen carrier gas was studied using a laboratory-scale, fixed bed adsorption system. Two kinds of activated carbon with dissimilar pore structures were used as adsorbents. The total concentration of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) in the source gas was 541 ng/Nm(3) and that of the 17 toxic 2,3,7,8-substituted PCDD/Fs 96.35 ng/Nm(3), accounting for 17.8% of the total original weight amount. Their toxic equivalent quantity (TEQ) was 8.31 ng I-TEQ/Nm(3). For both activated carbons, the removal efficiencies of the ten PCDD/F homologue groups rise with chlorine substitution number. The removal efficiencies vary approximately as a power function of vapor pressure (correlation coefficients r(2) = 0.93 and 0.81, respectively). Competitive adsorption and desorption occur as adsorption time went on, causing elution of the lower chlorinated homologues, i.e. tetra-CDD/F and Penta-CDD/F congeners. In addition, there are significantly different concentration distributions for isomers in the same homologue groups. However, their removal efficiencies have weak correlation with their initial concentrations. The correlation coefficients are from -0.47 to 0.32 and from -0.57 to 0.46 respectively for the two kinds of activated carbons.


Assuntos
Benzofuranos/isolamento & purificação , Dioxinas/isolamento & purificação , Poluentes Ambientais/isolamento & purificação , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/isolamento & purificação , Adsorção , Carvão Vegetal/química
20.
J Environ Sci (China) ; 32: 135-45, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26040740

RESUMO

Dioxin production is a worldwide concern because of its persistence and carcinogenic, teratogenic, and mutagenic effects. The pyrolysis-chemical looping combustion process of disposing solid waste is an alternative to traditional solid waste incineration developed to reduce the dioxin production. Based on the equilibrium composition of the Deacon reaction, pyrolysis gas oxidized by seven common oxygen carriers, namely, CuO, NiO, CaSO4, CoO, Fe2O3, Mn3O4, and FeTiO3, is studied and compared with the pyrolysis gas directly combusted by air. The result shows that the activity of the Deacon reaction for oxygen carriers is lower than that for air. For four typical oxygen carriers (CuO, NiO, Fe2O3, and FeTiO3), the influences of temperature, pressure, gas composition, and tar on the Deacon reaction are discussed in detail. According to these simulation results, the dioxin production in China, Europe, the United States, and Japan is predicted for solid waste disposal by the pyrolysis-chemical looping combustion process. Thermodynamic analysis results in this paper show that chemical looping combustion can reduce dioxin production in the disposal of solid waste.


Assuntos
Poluentes Atmosféricos/isolamento & purificação , Dioxinas/isolamento & purificação , Incineração/métodos , Eliminação de Resíduos/métodos , Poluentes Atmosféricos/química , Cloro/química , Simulação por Computador , Dioxinas/química , Temperatura Alta , Oxigênio/química , Pressão , Termodinâmica
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