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1.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361786

RESUMO

Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.


Assuntos
Antioxidantes/farmacologia , Betula/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Acetaldeído/antagonistas & inibidores , Acetaldeído/farmacologia , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Betula/classificação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Malondialdeído/antagonistas & inibidores , Camundongos , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Casca de Planta/classificação , Extratos Vegetais/química , Polônia , Superóxidos/antagonistas & inibidores , Triterpenos/química , Triterpenos/isolamento & purificação
2.
Carbohydr Polym ; 256: 117516, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33483037

RESUMO

A novel polysaccharide (MFP1P) was isolated from Fructus Mori, followed by purification via DEAE-52 cellulose and 27 % ethanol fraction. The MFP1P had the molecular weight of 56.78 kDa and the total sugar content of 93.32±0.54 %. And the MFP1P is mainly composed of glucose, galactose, galacturonic acid and mannose with molar ratio of 66.62 %, 13.94 %, 18.24 % and 1.20 %, respectively. MFP1P was mainly composed of →3)-α-D-Gal (1→, ß-D-Man-(1→ and →6)-α-D-Glc (1→ glycosidic bond and showed a spherical chain conformation with uniform distribution in solution. The MFP1P exhibited great antioxidant activity with oxygen-free radical absorption capacity (ORAC) values of 291.63±6.81 µmol TE/g and MDA IC50 of 0.289±0.022 mg/mL.


Assuntos
Antioxidantes/química , Frutas/química , Fígado/efeitos dos fármacos , Morus/química , Oxidantes/antagonistas & inibidores , Polissacarídeos/química , Amidinas/antagonistas & inibidores , Amidinas/química , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Sequência de Carboidratos , Fracionamento Químico/métodos , Misturas Complexas/química , Galactose/química , Galactose/isolamento & purificação , Glucose/química , Glucose/isolamento & purificação , Ácidos Hexurônicos/química , Ácidos Hexurônicos/isolamento & purificação , Fígado/metabolismo , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Manose/química , Manose/isolamento & purificação , Camundongos , Peso Molecular , Oxidantes/química , Extratos Vegetais/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia
3.
Int J Mol Sci ; 21(19)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33019601

RESUMO

The feed industry continuously seeks new molecules with antioxidant capacity since oxidative stress plays a key role in intestinal health. To improve screening of new antioxidants, this study aims to set up an assay to assess oxidative stress in the porcine small intestinal epithelial cell line IPEC-J2 using plate-reader-based analysis of fluorescence. Two oxidants, H2O2 and menadione, were tested at 1, 2 and 3 mM and 100, 200 and 300 µM, respectively. Trolox (2 mM) was used as the reference antioxidant and the probe CM-H2DCFDA was used to indicate intracellular oxidative stress. Cell culture, reactive oxygen species (ROS) production and assessment conditions were optimized to detect a significant ROS accumulation that could be counteracted by pre-incubation with trolox. Menadione (200 µM) reproducibly increased ROS levels, H2O2 failed to do so. Trolox significantly decreased intracellular ROS levels in menadione (200 µM)-exposed cells in a consistent way. The system was further used to screen different concentrations of the commercially available antioxidant ELIFE®. Concentrations between 100 and 200 ppm protected best against intracellular ROS accumulation. In conclusion, the combination of CM-H2DCFDA fluorescence analysis by a plate-reader, trolox as a reference antioxidant and 200 µM of menadione as a stressor agent, provides a replicable and reliable medium-throughput setup for the evaluation of intracellular oxidative stress in IPEC-J2 cells.


Assuntos
Antioxidantes/farmacologia , Cromanos/farmacologia , Células Epiteliais/efeitos dos fármacos , Ensaios de Triagem em Larga Escala , Vitamina K 3/antagonistas & inibidores , Ração Animal , Animais , Linhagem Celular , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Fluoresceínas/química , Corantes Fluorescentes/química , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Intestino Delgado/citologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Suínos , Vitamina K 3/farmacologia
4.
Int J Mol Sci ; 21(11)2020 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-32486511

RESUMO

Ascorbic acid (AscH2) is one of the most important vitamins found in the human diet, with many biological functions including antioxidant, chelating, and coenzyme activities. Ascorbic acid is also widely used in a medical practice especially for increasing the iron absorption and as an adjuvant therapeutic in the iron chelation therapy, but its mode of action and implications in the iron metabolism and toxicity are not yet clear. In this study, we used UV-Vis spectrophotometry, NMR spectroscopy, and EPR spin trapping spectroscopy to investigate the antioxidant/pro-oxidant effects of ascorbic acid in reactions involving iron and the iron chelator deferiprone (L1). The experiments were carried out in a weak acidic (pH from 3 to 5) and neutral (pH 7.4) medium. Ascorbic acid exhibits predominantly pro-oxidant activity by reducing Fe3+ to Fe2+, followed by the formation of dehydroascorbic acid. As a result, ascorbic acid accelerates the redox cycle Fe3+ ↔ Fe2+ in the Fenton reaction, which leads to a significant increase in the yield of toxic hydroxyl radicals. The analysis of the experimental data suggests that despite a much lower stability constant of the iron-ascorbate complex compared to the FeL13 complex, ascorbic acid at high concentrations is able to substitute L1 in the FeL13 chelate complex resulting in the formation of mixed L12AscFe complex. This mixed chelate complex is redox stable at neutral pH = 7.4, but decomposes at pH = 4-5 during several minutes at sub-millimolar concentrations of ascorbic acid. The proposed mechanisms play a significant role in understanding the mechanism of action, pharmacological, therapeutic, and toxic effects of the interaction of ascorbic acid, iron, and L1.


Assuntos
Ácido Ascórbico/química , Deferiprona/farmacologia , Ferro/química , Oxidantes/química , Quelantes/química , Quelantes/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Radical Hidroxila/química , Quelantes de Ferro/farmacologia , Espectroscopia de Ressonância Magnética , Oxidantes/antagonistas & inibidores , Oxirredução , Oxigênio/química , Espécies Reativas de Oxigênio/química , Espectrofotometria Ultravioleta
5.
Molecules ; 25(6)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168811

RESUMO

Phenolamines and flavonoids are two important components in bee pollen. There are many reports on the bioactivity of flavonoids in bee pollen, but few on phenolamines. This study aims to separate and characterize the flavonoids and phenolamines from rape bee pollen, and compare their antioxidant activities and protective effects against oxidative stress. The rape bee pollen was separated to obtain 35% and 50% fractions, which were characterized by HPLC-ESI-QTOF-MS/MS. The results showed that the compounds in 35% fraction were quercetin and kaempferol glycosides, while the compounds in 50% fraction were phenolamines, including di-p-coumaroyl spermidine, p-coumaroyl caffeoyl hydroxyferuloyl spermine, di-p-coumaroyl hydroxyferuloyl spermine, and tri-p-coumaroyl spermidine. The antioxidant activities of phenolamines and flavonoids were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays. It was found that the antioxidant activity of phenolamines was significantly higher than that of flavonoids. Moreover, phenolamines showed better protective effects than flavonoids on HepG2 cells injured by AAPH. Furthermore, phenolamines could significantly reduce the reactive oxygen species (ROS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and increase the superoxide dismutase (SOD) and glutathione (GSH) levels. This study lays a foundation for the further understanding of phenolamines in rape bee pollen.


Assuntos
Antioxidantes/química , Glicosídeos/química , Quempferóis/química , Pólen/química , Quercetina/química , Espermidina/química , Espermina/química , Alanina Transaminase/genética , Alanina Transaminase/metabolismo , Amidinas/antagonistas & inibidores , Amidinas/farmacologia , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Abelhas , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Expressão Gênica/efeitos dos fármacos , Glutationa/genética , Glutationa/metabolismo , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células Hep G2 , Humanos , Quempferóis/isolamento & purificação , Quempferóis/farmacologia , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Picratos/antagonistas & inibidores , Picratos/química , Extratos Vegetais/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/química , Espermidina/análogos & derivados , Espermidina/isolamento & purificação , Espermidina/farmacologia , Espermina/análogos & derivados , Espermina/isolamento & purificação , Espermina/farmacologia , Ácidos Sulfônicos/antagonistas & inibidores , Ácidos Sulfônicos/química , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
7.
Mol Med Rep ; 20(2): 1499-1508, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257486

RESUMO

Geniposide, as a type of iridoid glycoside, has antioxidative capacity. However, the mechanism underlying the effect of geniposide in cadmium (Cd)­induced osteoblast injury remains only partly elucidated. In the present study, Cell Counting Kit­8 (CCK­8) was used to determine MC­3T3­E1 cell viability. Flow cytometry was used to determine the rate of apoptosis and levels of reactive oxygen species (ROS). Oxidative stress­related factors were assessed using enzyme­linked immunosorbent method (ELISA). Quantitative real­time polymerase chain reaction (qPCR) and western blotting were used to evaluate apoptosis­ and bone formation­related genes and nuclear factor erythroid 2­related factor (Nrf2) signaling. It was demonstrated that geniposide increased the viability of the Cd­treated MC­3T3­E1 cells. Geniposide decreased apoptosis and ROS accumulation compared to these parameters in the Cd group. Geniposide attenuated oxidative stress­related factors, malondialdehyde and lactate dehydrogenase and increased antioxidant key enzyme superoxidase dismutase (SOD). The expression levels of Bax, Bcl­2 and survivin were modulated by geniposide. Additionally, the mRNA and protein expression of the receptor activator of NF­κB ligand (RANKL) and osterix were significantly increased, while osteoprotegerin was decreased by geniposide treatment compared to the Cd groups. Geniposide also enhanced Nrf2, heme oxygenase­1 (HO­1) and NAD(P)H quinone dehydrogenase 1 (NQO1) expression. The present study identified a potential agent for the treatment of Cd­induced osteoblast injury.


Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/antagonistas & inibidores , Iridoides/farmacologia , Fator 2 Relacionado a NF-E2/genética , Oxidantes/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Cloreto de Cádmio/farmacologia , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Malondialdeído/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Survivina/genética , Survivina/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
8.
Biofactors ; 45(4): 563-574, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31131946

RESUMO

Isoflavones are one group of the major flavonoids and possess multiple biological activities due to their antioxidant properties. However, a clear antioxidant mechanism of dietary isoflavones is still remained to be answered. In this study, the effects of isoflavones on the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway and the underlying molecular mechanisms were investigated. Results showed that isoflavones are potential Nrf2-ARE activators while their activities were structure dependent. Biochanin A (BCA), an O-methylated isoflavone with low direct antioxidant activity, can effectively protect HepG2 cells against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage via activation of the Nrf2 signaling, and thereby the induction of downstream cytoprotective enzymes including NAD(P)H quinone oxidoreductase-1, heme oxygenasae-1, and glutamate-cysteine ligase catalytic subunit. A molecular docking study revealed that BCA could directly bind into the pocket of Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1), a cytoplasmic suppressor of Nrf2, to facilitate Nrf2 activation. The upstream mitogen-activated protein kinase (MAPK) pathways were also involved in the activation of Nrf2 signaling. These findings indicate that the protective actions of dietary isoflavones against oxidative damage may be at least partly due to their ability to enhance the intracellular antioxidant response system by modulating the Nrf2-ARE signaling pathway.


Assuntos
Elementos de Resposta Antioxidante/efeitos dos fármacos , Antioxidantes/farmacologia , Genisteína/farmacologia , Proteínas Quinases Ativadas por Mitógeno/genética , Fator 2 Relacionado a NF-E2/genética , Espécies Reativas de Oxigênio/antagonistas & inibidores , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Células Hep G2 , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NADH NADPH Oxirredutases/genética , NADH NADPH Oxirredutases/metabolismo , Fator 2 Relacionado a NF-E2/agonistas , Fator 2 Relacionado a NF-E2/metabolismo , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , terc-Butil Hidroperóxido/antagonistas & inibidores , terc-Butil Hidroperóxido/farmacologia
9.
J Appl Oral Sci ; 27: e20180108, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30673028

RESUMO

OBJECTIVE: This study aims to evaluate the clinical and biochemical (oxidative stress and pro-inflammatory mediators) effects of the gaseous ozone use accompanied by scaling and root planning (SRP) in periodontal treatment. MATERIAL AND METHODS: The study population consisted of 40 patients with chronic periodontitis (CP) randomly sorted into two groups of 20. The experimental group received SRP plus 3 watts gaseous ozone in two separate applications five days apart, whereas the control group received SRP plus placebo. Clinical periodontal parameters were assayed and saliva samples were taken before the initial and one month after the second treatment. Periodontal examination assessed plaque index (PI), gingival index (GI), probing depth, and clinical attachment level (CAL). Total antioxidant status (TAS), total oxidant status (TOS), nitric oxide (NO), 8-hydroxy-2'-deoxyguanosine (8-OHdG), myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), and transforming growth factor-beta (TGF-ß) levels were evaluated from saliva samples. RESULTS: Changes following treatment in PI, GI, probing depth, and CAL scores were similar for both groups (p>0.05). Of note, TGF-ß levels were observed to be higher in the treatment group than in controls (p<0.05). Changes in 8-OHdG, TAS, TOS, NO, MPO, GSH and MDA levels, however, were not significantly different between groups (p>0.05). CONCLUSION: The findings of this study indicate that SRP plus gaseous ozone versus SRP alone does not correlate to a significant improvement in periodontal recovery.


Assuntos
Periodontite Crônica/terapia , Oxidantes Fotoquímicos/uso terapêutico , Ozônio/uso terapêutico , Aplainamento Radicular/métodos , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Antioxidantes/análise , Periodontite Crônica/patologia , Índice de Placa Dentária , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Glutationa/análise , Humanos , Masculino , Malondialdeído/análise , Pessoa de Meia-Idade , Óxido Nítrico/análise , Oxidantes/antagonistas & inibidores , Índice Periodontal , Peroxidase/análise , Reprodutibilidade dos Testes , Saliva/química , Estatísticas não Paramétricas , Fatores de Tempo , Fator de Crescimento Transformador beta/análise , Resultado do Tratamento
10.
Colloids Surf B Biointerfaces ; 173: 742-750, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30384271

RESUMO

The interactions and the protective effect of epigallocatechin gallate (EGCG) on human erythrocytes (RBC) and molecular models of its membrane were investigated. The latter consisted of bilayers built- up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. X-ray diffraction and differential scanning calorimetry experiments showed that EGCG induced significant structural and thermotropic perturbations in multilayers and vesicles of DMPC; however, these effects were not observed in DMPE. Fluorescence spectroscopy results revealed that EGCG produced alterations of the molecular dynamics at the level of the hydrophobic-hydrophilic interface in DMPC vesicles, and in isolated unsealed human erythrocyte membranes (IUM). EGCG also induced morphological alterations in RBC from their normal discoid form to echinocytes. These outcomes indicate that EGCG molecules were located in the outer monolayer of the erythrocyte membrane. The assessment of EGCG protective effect demonstrated that it inhibits the morphological alterations and lysis induced by HClO to human erythrocytes. The results obtained from this study suggest that the insertion of EGCG into the outer monolayer of the erythrocyte membrane might prevent the access and deleterious effects of oxidant molecules such as HClO and free radicals into the red cells, protecting them from oxidative damage.


Assuntos
Antioxidantes/farmacologia , Catequina/análogos & derivados , Membrana Eritrocítica/efeitos dos fármacos , Ácido Hipocloroso/antagonistas & inibidores , Oxidantes/antagonistas & inibidores , Antioxidantes/química , Catequina/química , Catequina/farmacologia , Dimiristoilfosfatidilcolina/química , Membrana Eritrocítica/química , Hemólise/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ácido Hipocloroso/farmacologia , Cinética , Bicamadas Lipídicas/química , Oxidantes/farmacologia , Fosfatidiletanolaminas/química , Espectrometria de Fluorescência , Termodinâmica
11.
Free Radic Res ; 52(6): 724-736, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29669446

RESUMO

A series of new di- and polyamine-caffeine analogues were synthesised and characterised by NMR, FT-IR, and MS spectroscopic methods. To access the stability of the investigated caffeine analogues, molecular dynamic simulations were performed in NAMD 2.9 assuming CHARMM36 force field. To evaluate the antioxidant capacity of new compounds, three different antioxidant assays were used, namely 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH•) scavenging activity, ferrous ions (Fe2+) chelating activity, and Fe3+→Fe2+reducing ability. In vitro, the ability of new derivatives to protect human erythrocytes against oxidative haemolysis induced by free radical from 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) was estimated. The cytotoxic activity was tested using MCF-7 breast cancer cells and human erythrocytes. All compounds showed the antioxidant capacity depending mostly on their ferrous ions chelating activity. In the presence of AAPH, some derivatives were able to effectively inhibit the oxidative haemolysis. Two derivatives, namely 8-(methyl(2-(methylamino)ethyl)-amino)caffeine and 8-(methyl(3-(methylamino)propyl)amino)caffeine, showed cytotoxic activity against MCF-7 breast cancer cells but not against human erythrocytes. Therefore, it is concluded that the selected di- and polyamine caffeine analogues, depending on their chemical structure, were able to minimise the oxidative stress and to inhibit the tumour cell growth. The confirmed antioxidant and cytotoxic properties of some caffeine derivatives make them attractive for potential applications in food or pharmaceutical industries.


Assuntos
Antioxidantes/farmacologia , Cafeína/farmacologia , Quelantes/farmacologia , Citotoxinas/farmacologia , Oxidantes/antagonistas & inibidores , Amidinas/antagonistas & inibidores , Amidinas/farmacologia , Antioxidantes/síntese química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Cafeína/análogos & derivados , Cafeína/síntese química , Sobrevivência Celular/efeitos dos fármacos , Quelantes/síntese química , Citotoxinas/síntese química , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Ferro/química , Células MCF-7 , Especificidade de Órgãos , Oxidantes/farmacologia , Oxirredução , Picratos/antagonistas & inibidores , Picratos/química , Poliaminas/química , Relação Estrutura-Atividade
12.
Free Radic Res ; 52(5): 544-555, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29526117

RESUMO

Although previous studies have reported the protective effect of glucagon-like peptide-1 (GLP-1) in diabetes nephropathy, the molecular mechanism such as nephroprotection remains elusive. In this study, we explored the molecular mechanism of exendin-4 as an GLP-1 receptor agonist for the treatment of tert-butyl hydroperoxide (t-BHP)-induced injury in mouse glomerulus mesangial cells (SV40 MES 13 cells) via an NMR-based metabonomic analysis. We found that exendin-4 protected mesangial cells from t-BHP-mediated toxicity, decreased the percentage of t-BHP-treated cells undergoing apoptosis, and restored glucose consumption in the t-BHP-treated group. A supervised partial least-squares discriminant analysis (PLS-DA) revealed that the metabolic profiles could be distinguished between the control, t-BHP-treated, and exendin-4-pretreated groups. Our findings indicate that exendin-4 pretreatment can cause distinct changes in energy, glycerol phospholipid, and amino acid metabolism. Our study provides novel insight into the metabolic mechanism of exendin-4-mediated nephroprotective effects.


Assuntos
Hipoglicemiantes/farmacologia , Células Mesangiais/efeitos dos fármacos , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Peçonhas/farmacologia , terc-Butil Hidroperóxido/antagonistas & inibidores , Aminoácidos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Exenatida , Glucose/metabolismo , Glicerofosfolipídeos/metabolismo , Espectroscopia de Ressonância Magnética , Células Mesangiais/citologia , Células Mesangiais/metabolismo , Metabolômica/métodos , Camundongos , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Análise de Componente Principal , terc-Butil Hidroperóxido/farmacologia
13.
Recent Pat Anticancer Drug Discov ; 13(2): 224-239, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29446748

RESUMO

BACKGROUND: Tumor cells may be expressed as a result of oxidative stress. The extent of oxidative stress correlates with the aggressive and metastatic potency of cancer. OBJECTIVE: One simple way to control prostate cancer is through chemoprevention which refers to the administration of natural or synthetic agents to block, reverse, or delay the process of carcinogenesis. The most chemopreventive agents are antioxidants in nature. METHODS: In this review, we summarized the effects of dietary antioxidants with a focus on their molecular mechanisms and possible roles in the treatment of prostate cancer cells. We also reported the recent outcomes of laboratory and/or clinical trials of antioxidants in prostate cancer patients. RESULTS: Numerous pre-clinical studies showed that antioxidants protect DNA against being damaged by Reactive Oxygen Species (ROS), thereby genetic mutations causing cancer are likely to be prevented. However, the clinical trial results showed that antioxidants have yielded mixed outcomes or benefitted only a subgroup of the population. CONCLUSION: A greater understanding of the molecular events associated with antioxidants will enhance the development of treatment and could result in better strategies for the chemoprevention of prostate cancer. Recent patents also suggest that anti-oxidant compounds can be effective for the prevention and the treatment of prostate cancer.


Assuntos
Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Neoplasias da Próstata/prevenção & controle , Animais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Quimioprevenção/métodos , Quimioprevenção/normas , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/normas , Humanos , Masculino , Oxidantes/antagonistas & inibidores , Oxidantes/metabolismo , Estresse Oxidativo/fisiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo
14.
Mol Med Rep ; 17(3): 4163-4172, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29328415

RESUMO

The endogenous neurotransmitter, noradrenaline, exerts anti-inflammatory and neuroprotective effects in vivo and in vitro. Reduced noradrenaline levels results in increased inflammation and neuronal damage. The primary source of noradrenaline in the central nervous system is tyrosine hydroxylase (TH)­positive neurons, located in the locus coeruleus (LC). TH is the rate­limiting enzyme for noradrenaline synthesis; therefore, regulation of TH protein expression and intrinsic enzyme activity represents the central means for controlling the synthesis of noradrenaline. Catalpol is an iridoid glycoside purified from Rehmannia glutinosa Libosch, which exerts a neuroprotective effect in multiple sclerosis (MS). The present study used an experimental mouse model of autoimmune encephalomyelitis to verify the neuroprotective effects of catalpol. Significant improvements in the clinical scores were observed in catalpol­treated mice. Furthermore, catalpol increased TH expression and increased noradrenaline levels in the spinal cord. In primary cultures, catalpol exerted a neuroprotective effect in rat LC neurons by increasing the noradrenaline output. These results suggested that drugs targeting LC survival and function, including catalpol, may be able to benefit patients with MS.


Assuntos
Anti-Inflamatórios/farmacologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Glucosídeos Iridoides/farmacologia , Locus Cerúleo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Norepinefrina/biossíntese , Amidinas/antagonistas & inibidores , Amidinas/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Benzilaminas/administração & dosagem , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Feminino , Regulação da Expressão Gênica , Imunização , Injeções Intraperitoneais , Glucosídeos Iridoides/isolamento & purificação , Locus Cerúleo/imunologia , Locus Cerúleo/patologia , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/administração & dosagem , Neurônios/imunologia , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Neurotransmissores/agonistas , Neurotransmissores/biossíntese , Norepinefrina/agonistas , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Fragmentos de Peptídeos/administração & dosagem , Cultura Primária de Células , Rehmannia/química , Medula Espinal/efeitos dos fármacos , Medula Espinal/imunologia , Medula Espinal/patologia , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/imunologia
15.
Pharm Biol ; 56(1): 51-59, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29275696

RESUMO

CONTEXT: Actinobacteria are a precious source of novel bioactive metabolites with potential pharmaceutical applications. OBJECTIVES: Representatives of 11 genera of rare Actinobacteria were selected for the evaluation of antioxidant activity. MATERIAL AND METHODS: Fermentation broths of the Actinobacteria were extracted and dosage of 10 to 2000 µg/mL were applied for in vitro antioxidant-related bioassays. Cytotoxicity was assessed at the concentration of 2.5-20 µg/mL. RESULTS: In the DPPH scavenging activity, 15 out of 52 extracts showed 17.0-26.8% activity in quantitative evaluation. Metabolites of five prominent antioxidant producing strains protected the DNA (pUC19) against UV-induced photolyzed H2O2-oxidative degradation. The potent antioxidant extracts inhibited two oxidative enzymes of xanthine oxidase in the range of 17.5-45.2% (three extracts had IC50 less than allopurinol) and lipoxygenase in the range of 36-55% (all five extracts had IC50 values less than daidzein). All these extracts could also protect eythrocytes from iron-induced hemolysis with ED50 values in a range of 0.014-1.25 mg/mL. Growth restoration of the yeast cells lacking the sod1 gene was observed by the antioxidant metabolite of Saccharothrix ecbatanensis UTMC 537 at the concentration of 1 mg/mL. CONCLUSIONS: The presence of nonidentical metabolites might be responsible for antioxidant and enzyme inhibitory activities of S. ecbatanensis, newly described actinobacterium in family Pseudonocardiaceae. The scavenging of the free electrons, protection of DNA and model yeast cells against oxidative stress, in addition to the inhibition of the oxidating enzymes are the main mechanisms of the antioxidant effect of the introduced resource in this study.


Assuntos
Actinobacteria/metabolismo , Antioxidantes/metabolismo , Oxidantes/antagonistas & inibidores , Oxidantes/metabolismo , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Artemia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/metabolismo , Sequestradores de Radicais Livres/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos
16.
Eur J Med Chem ; 143: 854-865, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29223100

RESUMO

Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues.


Assuntos
Curcumina/farmacologia , Cetonas/farmacologia , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Oxidantes/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Curcumina/análogos & derivados , Curcumina/química , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Cetonas/química , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Oxidantes/metabolismo , Relação Estrutura-Atividade
17.
J Card Fail ; 23(12): 887-899, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28870731

RESUMO

BACKGROUND: Type 1 diabetes mellitus (DM) patients surviving myocardial infarction (MI) have substantially higher cardiovascular morbidity and mortality compared to their nondiabetic counterparts owing to the more frequent development of subsequent heart failure (HF). Neuregulin (NRG)-1ß is released from cardiac microvascular endothelial cells and acts as a paracrine factor via the ErbB family of tyrosine kinase receptors expressed in cardiac myocytes to regulate cardiac development and stress responses. Because myocardial NRG-1/ErbB signaling has been documented to be impaired during HF associated with type 1 DM, we examined whether enhancement of NRG-1ß signaling via exogenous administration of recombinant NRG-1ß could exert beneficial effects against post-MI HF in the type 1 diabetic heart. METHODS AND RESULTS: Type 1 DM was induced in male Sprague Dawley rats by a single injection of streptozotocin (STZ) (65 mg/kg). Two weeks after induction of type 1 DM, rats underwent left coronary artery ligation to induce MI. STZ-diabetic rats were treated with saline or NRG-1ß (100 µg/kg) twice per week for 7 weeks, starting 2 weeks before experimental MI. Residual left ventricular function was significantly greater in the NRG-1ß-treated STZ-diabetic MI group compared with the vehicle-treated STZ-diabetic MI group 5 weeks after MI as assessed by high-resolution echocardiography. NRG-1ß treatment of STZ-diabetic MI rats was associated with reduced myocardial fibrosis and apoptosis as well as decreased gene expression of key oxidant-producing enzymes. CONCLUSIONS: These results suggest that recombinant NRG-1ß may be a promising therapeutic for HF post-MI in the setting of type 1 DM.


Assuntos
Apoptose/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Neuregulina-1/administração & dosagem , Oxidantes/antagonistas & inibidores , Animais , Antioxidantes/administração & dosagem , Apoptose/fisiologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Progressão da Doença , Esquema de Medicação , Fibrose , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Humanos , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Oxidantes/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Molecules ; 22(9)2017 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-28885586

RESUMO

Natural products are considered as an important source for the discovery of new drugs to treat aging-related degenerative diseases and liver injury. The present study profiled the chemical constituents of a methanol extract from Senna singueana bark using HPLC-PDA-ESI-MS/MS and 36 secondary metabolites were identified. Proanthocyanidins dominated the extract. Monomers, dimers, trimers of (epi)catechin, (epi)gallocatechin, (epi)guibourtinidol, (ent)cassiaflavan, and (epi)afzelechin represented the major constituents. The extract demonstrated notable antioxidant activities in vitro: In DPPH (EC50 of 20.8 µg/mL), FRAP (18.16 mM FeSO4/mg extract) assays, and total phenolic content amounted 474 mg gallic acid equivalent (GAE)/g extract determined with the Folin-Ciocalteu method. Also, in an in vivo model, the extract increased the survival rate of Caenorhabditis elegans worms pretreated with the pro-oxidant juglone from 43 to 64%, decreased intracellular ROS inside the wild-type nematodes by 47.90%, and induced nuclear translocation of the transcription factor DAF-16 in the transgenic strain TJ356. Additionally, the extract showed a remarkable hepatoprotective activity against d-galactosamine (d-GalN) induced hepatic injury in rats. It significantly reduced elevated AST (aspartate aminotransferase), and total bilirubin. Moreover, the extract induced a strong cytoplasmic Bcl-2 expression indicating suppression of apoptosis. In conclusion, the bark extract of S. sengueana represents an interesting candidate for further research in antioxidants and liver protection.


Assuntos
Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Substâncias Protetoras/farmacologia , Senna (Planta)/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/genética , Bilirrubina/sangue , Compostos de Bifenilo/antagonistas & inibidores , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Catecóis/química , Catecóis/isolamento & purificação , Catecóis/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Galactosamina/toxicidade , Masculino , Metanol/química , Naftoquinonas/antagonistas & inibidores , Naftoquinonas/farmacologia , Oxidantes/antagonistas & inibidores , Oxidantes/farmacologia , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Picratos/antagonistas & inibidores , Casca de Planta/química , Extratos Vegetais/química , Proantocianidinas/química , Proantocianidinas/isolamento & purificação , Proantocianidinas/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Proteínas Proto-Oncogênicas c-bcl-2/agonistas , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Solventes/química
19.
Pharm Biol ; 55(1): 1843-1848, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28571528

RESUMO

CONTEXT: The leaves of Pyrola decorate H. Andr (Pyrolaceae), known as Luxiancao, have long been used for treating kidney deficiency, gastric haemorrhage and rheumatic arthritic diseases in traditional Chinese medicine. OBJECTIVE: The phytochemicals and antioxidant capacities in vitro of P. decorate leaves were investigated. MATERIALS AND METHODS: Ethanol, petroleum ether, acetidin, n-butyl alcohol and aqueous extracts of Pyrola decorate leaves were prepared by solvent sequential process, and then isolated and purified to obtain phytochemicals. Cell viability was measured by MTT assay. PC12 cells were pretreated for 24 h with different extractions of P. decorate leaves at concentrations of 0.1, 0.5, 1, 5 and 10 mg/mL, then H2O2 of 0.4 mM was added in all samples for an additional 2 h. The antioxidant capacities of betulin, ursolic acid and monotropein were determined in PC12 cells against H2O2 induced cytotoxicity in vitro as well. RESULTS: Nine compounds (1-9) were isolated and structurally determined by spectroscopic methods, especially 2D NMR analyses. Ethanol extract treated groups showed inhibitory activity with IC50 value of 10.83 mg/mL. Betulin, ursolic acid and monotropein were isolated from P. decorate, and demonstrated with IC50 values of 6.88, 6.15 and 6.13 µg/mL, respectively. DISCUSSION AND CONCLUSIONS: In conclusion, Pyrola decorate is a potential antioxidative natural plant and worth testing for further pharmacological investigation in the treatment of oxidative stress related neurological disease.


Assuntos
Antioxidantes/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Pyrola/química , Animais , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , China , Etanol/química , Etnofarmacologia , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/toxicidade , Iridoides/análise , Iridoides/química , Iridoides/isolamento & purificação , Iridoides/farmacologia , Estrutura Molecular , Neurônios/citologia , Fármacos Neuroprotetores/análise , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Oxidantes/antagonistas & inibidores , Oxidantes/toxicidade , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos , Solventes/química , Triterpenos/análise , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
20.
Free Radic Biol Med ; 110: 133-141, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28571752

RESUMO

Organic selenium and tellurium compounds are known for their broad-spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high-throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C. elegans) as a model for the assessment of pharmacological and toxicological parameters following exposure to two 4-phenylchalcogenil-7-chloroquinolines derivatives (PSQ for selenium and PTQ for tellurium-containing compounds). While non-lethal concentrations (NLC) of PTQ and PSQ attenuated paraquat-induced effects on survival, lifespan and oxidative stress parameters, lethal concentrations (LC) of PTQ and PSQ alone are able to impair these parameters in C. elegans. We also demonstrate that DAF-16/FOXO and SKN-1/Nrf2 transcription factors underlie the mechanism of action of these compounds, as their targets sod-3, gst-4 and gcs-1 were modulated following exposures in a daf-16- and skn-1-dependent manner. Finally, in accordance with a disturbed thiol metabolism in both LC and NLC, we found higher sensitivity of trxr-1 worm mutants (lacking the selenoprotein thioredoxin reductase 1) when exposed to PSQ. Finally, our study suggests new targets for the investigation of organochalcogen pharmacological effects, reinforcing the use of C. elegans as a powerful platform for preclinical approaches.


Assuntos
Antioxidantes/farmacologia , Caenorhabditis elegans/efeitos dos fármacos , Calcogênios/farmacologia , Compostos Organometálicos/farmacologia , Compostos Organosselênicos/farmacologia , Quinolinas/farmacologia , Telúrio/farmacologia , Animais , Antioxidantes/síntese química , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Calcogênios/síntese química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Longevidade/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Organometálicos/síntese química , Compostos Organosselênicos/síntese química , Oxidantes/antagonistas & inibidores , Oxidantes/toxicidade , Estresse Oxidativo , Paraquat/antagonistas & inibidores , Paraquat/toxicidade , Quinolinas/síntese química , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
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