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1.
Acta Crystallogr C Struct Chem ; 75(Pt 8): 1091-1101, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31380792

RESUMO

A new set of differently hydrated barium and strontium squarates, namely poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium] monohydrate], {[Ba(C4O4)(H2O)3]·H2O}n (1), poly[[diaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)strontium] monohydrate], {[Sr(C4O4)(H2O)2]·H2O}n (2), and poly[[triaqua(µ-1,2-dioxocyclobut-3-ene-1,2-diolato)barium/strontium(0.85/0.15)] monohydrate], {[Ba0.85Sr0.15(C4O4)(H2O)3]·H2O}n (3), is reported. The study of their crystal structures indicates that all the complexes crystallize in the triclinic space group P-1. Complexes 1 and 3 have a rare combination of squarate units coordinated through monodentate O atoms to two different metal atoms and through two bidentate O atoms to three different metal atoms. Furthermore, they have three coordinated water molecules to give a coordination number of nine. The squarate ligands in complex 2 exhibit two different coordination modes: (i) monodentate O atoms coordinated to four different Sr atoms and (ii) two monodentate O atoms coordinated to two different metal atoms with the other two O atoms bidentate to four different Sr atoms. All the compounds decompose to give the respective carbonates when heated to 800 °C, as evidenced by thermogravimetry/differential thermal analysis (TG-DTA), which are clusters of nanoparticles. Complexes 1 and 3 show additional endothermic peaks at 811 and 820 °C, respectively, indicating the phase transition of BaCO3 from an orthorhombic (α-Pmcn) to a trigonal phase (ß-R3m). All three complexes have significant DNA-binding constants, ranging from 2.45 × 104 to 9.41 × 104 M-1 against EB-CT (ethidium bromide-calf thymus) DNA and protein binding constants ranging from 1.1 × 105 to 8.6 × 105 with bovine serum albumin. The in vitro cytotoxicity of the complexes is indicated by the IC50 values, which range from 128.8 to 261.3 µg ml-1. Complex 3 shows better BSA binding, antioxidant activity against the DPPH radical and cytotoxicity than complexes 1 and 2.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ciclobutanos/farmacologia , Depuradores de Radicais Livres/farmacologia , Substâncias Intercalantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Bário/química , Bovinos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Cristalografia por Raios X , Ciclobutanos/síntese química , Ciclobutanos/química , Ciclobutanos/metabolismo , DNA/metabolismo , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Humanos , Ligações de Hidrogênio , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/metabolismo , Ligantes , Células MCF-7 , Estrutura Molecular , Ligação Proteica , Soroalbumina Bovina/metabolismo , Estrôncio/química , Água/química
2.
Expert Opin Investig Drugs ; 28(7): 593-603, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31185180

RESUMO

INTRODUCTION: Oxidative stress toxicity (OST) has been implicated in almost all pathological conditions. Despite the widespread use of natural antioxidants, no pharmaceutical antioxidants have yet been developed or prescribed in medical practise. Antioxidant drugs such as Deferiprone and N-acetylcysteine can target essential pathways of OST in many pathological conditions. The pharmacological parameters required by antioxidant drugs in relation to the OST target characteristics include the determination of the therapeutic index, ADMET and drug interactions. Antioxidant drug development efforts are currently targeting the treatment of severe diseases with no proven effective therapies. AREAS COVERED: This article addresses the damaging effects of OST, prospects for the development of pharmaceutical antioxidants and clinical studies using other drugs with antioxidant potential. EXPERT OPINION: Effective antioxidant therapeutic strategies should include the design of protocols for the inhibition of OST through iron chelation, administration of synthetic and natural antioxidants and enhancement of the antioxidant defences by increasing the production of endogenous antioxidants and activation of antioxidant mechanisms. Different therapeutic strategies apply in the use of antioxidant drugs for one or more targets, for prevention, treatment, or of post-treatment effects and for systematic, long-term or short-term applications. The design of new antioxidant drugs and effective protocols which can include Deferiprone and N-acetylcysteine combinations, could lead to the development of a new class of therapeutics for clinical use.


Assuntos
Antioxidantes/farmacologia , Depuradores de Radicais Livres/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Acetilcisteína/administração & dosagem , Acetilcisteína/farmacologia , Animais , Antioxidantes/administração & dosagem , Deferiprona/administração & dosagem , Deferiprona/farmacologia , Desenho de Drogas , Desenvolvimento de Medicamentos/métodos , Depuradores de Radicais Livres/administração & dosagem , Radicais Livres , Humanos , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/farmacologia , Terapia de Alvo Molecular
3.
Eur J Med Chem ; 177: 414-424, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158754

RESUMO

Due to the role of butyrylcholinesterase (BChE) in acetylcholine hydrolysis in the late stages of the Alzheimer's disease (AD), inhibitors of butyrylcholinesterase (BChE) have been recently envisaged, besides acetylcholinesterase (AChE) inhibitors, as candidates for treating mild-to-moderate AD. Herein, synthesis and AChE/BChE inhibition activity of some twenty derivatives of 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole (HHAI) is reported. Most of the newly synthesized HHAI derivatives achieved the inhibition of both ChE isoforms with IC50s in the micromolar range, with a structure-dependent selectivity toward BChE. Apparently, molecular volume and lipophilicity do increase selectivity toward BChE, and indeed the N2-(4-phenylbutyl) HHAI derivative 15d, which behaves as a mixed-type inhibitor, resulted the most potent (IC50 0.17 µM) and selective (>100-fold) inhibitor toward either horse serum and human BChE. Moreover, 15d inhibited in vitro self-induced aggregation of neurotoxic amyloid-ß (Aß) peptide and displayed neuroprotective effects in neuroblastoma SH-SY5Y cell line, significantly recovering (P < 0.001) cell viability when impaired by Aß1-42 and hydrogen peroxide insults. Overall, this study highlighted HHAI as useful and versatile scaffold for developing new small molecules targeting some enzymes and biochemical pathways involved in the pathogenesis of AD.


Assuntos
Azepinas/farmacologia , Inibidores da Colinesterase/farmacologia , Indóis/farmacologia , Fármacos Neuroprotetores/farmacologia , Peptídeos beta-Amiloides/metabolismo , Azepinas/síntese química , Azepinas/química , Azepinas/metabolismo , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Domínio Catalítico , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Relação Dose-Resposta a Droga , Desenho de Drogas , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Humanos , Indóis/síntese química , Indóis/química , Indóis/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , Fragmentos de Peptídeos/metabolismo , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Relação Estrutura-Atividade
4.
Food Chem Toxicol ; 131: 110535, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31154083

RESUMO

This study endeavours to investigate the phytochemical composition, biological properties and in vivo toxicity of methanol and dichloromethane extracts of Zaleya pentandra (L.) Jeffrey. Total bioactive contents, antioxidant (phosphomolybdenum and metal chelating, DPPH, ABTS, FRAP and CUPRAC) and enzyme inhibition (cholinesterases, tyrosinase α-amylase, and α-glucosidase) potential were assessed utilizing in vitro bioassays. UHPLC-MS phytochemical profiling was carried out to identify the essential compounds. The methanol extract was found to contain highest phenolic (22.60 mg GAE/g) and flavonoid (31.49 mg QE/g) contents which correlate with its most significant radical scavenging, reducing potential and tyrosinase inhibition. The dichloromethane extract was most potent for phosphomolybdenum, ferrous chelation, α-amylase, α-glucosidase, and cholinesterase inhibition assays. UHPLC-MS analysis of methanol extract unveiled to identify 11 secondary metabolites belonging to five sub-groups, i.e., phenolic, alkaloid, carbohydrate, terpenoid, and fatty acid derivatives. Additionally, in vivo toxicity was conducted for 21 days and the methanol extract at different doses (150, 200, 250 and 300 mg/kg) was administered in experimental chicks divided into five groups each containing five individuals. Different physical, haematological and biochemical parameters along with the absolute and relative weight of visceral body organs were studied. Overall, no toxic effect was noted for the extract at tested doses.


Assuntos
Aizoaceae/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Administração Oral , Animais , Galinhas , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/toxicidade , Depuradores de Radicais Livres/administração & dosagem , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Metanol/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química
5.
Food Chem Toxicol ; 131: 110539, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158404

RESUMO

The chemical characterization and protective role against ethanol-induced gastric ulcerated rats of a polysaccharide fraction from Bletilla striata (BSP) collected by ultrafiltration membrane approach were evaluated. This BSP faction was consisted of mannose and glucose at a molar ratio of 2.4:1 approximately, with a molecular weight of 146 KDa. FT-IR, NMR and XRD spectra indicated that BSP faction contained α-Man and ß-Glc residues with low overall crystallinity. The polysaccharide exhibited significant scavenging activities of ABTS and FRAP, as well as non-toxicity against human gastric epithelial GES-1 cells. Oral administration with 100 mg/kg of BSP for 3 days continuously could significantly prevent the formation of ethanol-induced gastric mucosal lesion. It could also reduce the levels of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and IL-18, and MPO activity in gastric tissue. Additionally, the BSP faction exhibited antioxidant activity, increased the content of PEG2 as a defensive factor, and suppressed MAPK/NF-κB signaling pathway in gastric tissue. These results indicated that the gastroprotective activity of BSP faction could be attributed to the reduction of pro-inflammatory cytokines and oxidative stress and the inhibition of MAPK/NF-κB pathways. Our results provided substantial evidence that BSP could be a promising phytomedicine for gastric ulcer prevention.


Assuntos
Fármacos Gastrointestinais/farmacologia , Orchidaceae/química , Polissacarídeos/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Linhagem Celular , Citocinas/metabolismo , Dinoprostona/metabolismo , Etanol , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/toxicidade , Humanos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/toxicidade , Ratos , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
6.
Eur J Med Chem ; 174: 216-225, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31042617

RESUMO

The identification of a valid therapeutic treatment for Alzheimer's disease (AD) represents nowadays an urgent and still unmet medical need, since currently available anti-AD drugs only relieve symptoms and show a modest efficacy. Recent evidence indicates that multi-target-directed ligands (MTDLs) can potentially provide an effective strategy to develop innovative therapies directed towards the onset and progression of this multifactorial neurodegenerative disorder. In this work we designed, synthesized and evaluated a new series of MTDLs bearing the rivastigmine skeleton (ChE-inhibitor) linked to known metal-chelating moieties with linkers of different length. For all the novel derivatives, AChE/BuChE inhibitory activity, ROS scavenging activity and potential cytotoxicity have been assessed. For the best compound (4), copper chelating properties and neuroprotective effects were also evaluated. Our data demonstrated that hybrid derivative 4 is able to effectively inhibit AChE and BuChE and to chelate copper, showing a protective action on neurons. These results, although preliminary, indicate that compound 4 can be considered as a possible hit molecule for the development of new anti-AD MTDLs.


Assuntos
Quelantes/farmacologia , Complexos de Coordenação/farmacologia , Cobre/química , Fármacos Neuroprotetores/farmacologia , Rivastigmina/análogos & derivados , Rivastigmina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Butirilcolinesterase/metabolismo , Linhagem Celular Transformada , Quelantes/síntese química , Quelantes/toxicidade , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/toxicidade , Complexos de Coordenação/síntese química , Complexos de Coordenação/toxicidade , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Camundongos , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/toxicidade , Rivastigmina/síntese química , Rivastigmina/toxicidade
7.
Molecules ; 24(9)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052486

RESUMO

Morels famous for their taste and nutrition are in short supply all over the world although they were considered as one of the most highly prized edible and medicinal mushrooms. Because of the limitation of resource and cultivation technology, fermentation of edible mushroom was gradually applied to nutrient, bioactivity and breeder seed preparation. At present, there are more reports on sugar and amino acid but less on other components. Morchella sp. YDJ-ZY-1 was isolated from the wild fruiting body by the spores releasing method in Zunyi Guizhou province in Southwest China and identified based on phenotype and genotype characteristics. Chemical compositions of YDJ-ZY-1 were investigated from liquid fermentation that will lay the foundation for further development and utilization. Four pyranoids (1-4) and 2-(1-oxo-2-hydroxyethyl) furan (5), linoleic acid (6), Morelin (2-hydroxy-cinnamic acid methyl ester, (7) and 1-O-ß-d-ribofuranose-Morelin (8) were obtained from EtOAc extraction and elucidated by spectral data. Product 4 and 8 were new compounds and 7 was isolated from nature for the first time. Antiradical activity was evaluated by free radical scavenging effect on DPPH (1,1-Diphenyl-2-picrylhydrazyl radical 2,2-Diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl). Compound 5 exhibited strong antiradical activity while compounds 1 and 2 exhibited moderate activity. Thus, incubation of Morchella sp YDJ-ZY-1 separated from the wild fruit body afforded eight compounds. Secondary metabolites with new structures were mined from fermentation of Morchella sp. and antiradical activity was evaluated.


Assuntos
Ascomicetos/metabolismo , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Fermentação , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Metabolismo Secundário , Agaricales , Ascomicetos/classificação , Ascomicetos/ultraestrutura , Produtos Biológicos/química , China , Depuradores de Radicais Livres/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular
8.
Mar Drugs ; 17(5)2019 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035632

RESUMO

In this report, protein hydrolysate (TGH) of blood cockle (Tegillarca granosa) was prepared using a two-enzyme system (Alcalase treatment for 1.5 h following Neutrase treatment for 1.5 h). Subsequently, six antioxidant peptides were isolated from TGH using ultrafiltration and chromatography methods, and their amino acid sequences were identified as EPLSD, WLDPDG, MDLFTE, WPPD, EPVV, and CYIE with molecular weights of 559.55, 701.69, 754.81, 513.50, 442.48, and 526.57 Da, respectively. In which, MDLFTE and WPPD exhibited strong scavenging activities on DPPH radical (EC50 values of 0.53 ± 0.02 and 0.36 ± 0.02 mg/mL, respectively), hydroxy radical (EC50 values of 0.47 ± 0.03 and 0.38 ± 0.04 mg/mL, respectively), superoxide anion radical (EC50 values of 0.75 ± 0.04 and 0.46 ± 0.05 mg/mL, respectively), and ABTS cation radical (EC50 values of 0.96 ± 0.08 and 0.54 ± 0.03 mg/mL, respectively). Moreover, MDLFTE and WPPD showed high inhibiting ability on lipid peroxidation. However, MDLFTE and WPPD were unstable and could not retain strong antioxidant activity at high temperatures (>80 °C for 0.5 h), basic pH conditions (pH > 9 for 2.5 h), or during simulated GI digestion. In addition, the effect of simulated gastrointestinal digestion on TGP4 was significantly weaker than that on MDLFTE. Therefore, MDLFTE and WPPD may be more suitable for serving as nutraceutical candidates in isolated forms than as food ingredient candidates in functional foods and products.


Assuntos
Organismos Aquáticos , Bivalves , Depuradores de Radicais Livres/farmacologia , Peptídeos/farmacologia , Hidrolisados de Proteína/química , Sequência de Aminoácidos , Animais , Suplementos Nutricionais , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Alimento Funcional , Temperatura Alta , Concentração de Íons de Hidrogênio , Peroxidação de Lipídeos/efeitos dos fármacos , Peptídeos/química , Peptídeos/isolamento & purificação , Hidrolisados de Proteína/isolamento & purificação
9.
Carbohydr Polym ; 216: 270-281, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047067

RESUMO

The fine structure and chain conformation of a heteropolysaccharide (PCIPS3) from mycelium of Paecilomyces cicadae were investigated via the analysis of HPLC, IR, methylation, NMR spectroscopy and multiangle light scattering. It was determined to be a 2.23 × 104 g/mol heteropolysaccharide primarily composed of glucose, galactose and mannose in a molar ratio of 23.8:2.1:1.0. The PCIPS3 backbone consisted of 1,4-linked α-d-Glcp and 1,4-linked 6-O-Me-α-d-Glcp residues, which were occasionally interrupted by branched ß-Galf residues through 1,6-linkage. Moreover, the α (0.60) from Mark-Houwink-Sakurada (MHS) equation suggested that PCIPS3 adopted a flexible chain conformation in 0.1 mol/L NaNO3 at 25 °C. The worm-like chains model parameters for PCIPS3 were estimated as following: ML = 437 nm-1, q = 0.46 nm and 0.79 nm, which were further evidenced by AFM. Furthermore, PCIPS3 showed excellent scavenging capacities of 2,2-diphenyl-1-picrylhydrazyl radical, superoxide radical, hydroxyl radical, ORAC radical and moderate immunomodulatory activity.


Assuntos
Depuradores de Radicais Livres/farmacologia , Polissacarídeos Fúngicos/farmacologia , Fatores Imunológicos/farmacologia , Paecilomyces/química , Animais , Configuração de Carboidratos , Sobrevivência Celular/efeitos dos fármacos , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/toxicidade , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Polissacarídeos Fúngicos/toxicidade , Radical Hidroxila/química , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/toxicidade , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Camundongos , Peróxidos/química , Células RAW 264.7 , Superóxidos/química , Fator de Necrose Tumoral alfa/metabolismo
10.
Carbohydr Polym ; 216: 97-106, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047086

RESUMO

Here, we identified inulin-type oligosaccharides with 3-13 degrees of polymerization from Morinda officinalis. Radical-scavenging assays showed that Inulins 4-7 had modest anti-oxidative effects. Inulins 4 and 5 dose-dependently increased human umbilical vein endothelial cell survival during hypoxia/re-oxygenation (H/R)-induced injury, and Inulin 5 promoted angiogenesis. Triplicate assays with the Affymetrix Human Transcriptome Array 2.0 showed that Inulin 5 exposure up-regulated genes associated with cell cycle progression, apoptosis, DNA replication and repair, ubiquitin-mediated proteolysis, the mitogen-activated protein kinase pathway, and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-signaling pathway. Flow cytometry, reverse transcription-quantitative polymerase chain reaction, and western blot experiments verified the microarray results and demonstrated that Inulin 5 influenced cell cycle progression and the PI3K-protein kinase B (PKB)-endothelial nitric oxide synthase (eNOS) pathway. Thus, inulin-type oligosaccharides from M. officinalis roots may protect against H/R-induced injury, primarily through an anti-oxidative effect, and promote angiogenesis by activating the PI3K-PKB-eNOS-signaling pathway.


Assuntos
Depuradores de Radicais Livres/farmacologia , Hipóxia/tratamento farmacológico , Inulina/farmacologia , Morinda/química , Oligossacarídeos/farmacologia , Indutores da Angiogênese/isolamento & purificação , Indutores da Angiogênese/farmacologia , Sequência de Carboidratos , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Depuradores de Radicais Livres/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Inulina/isolamento & purificação , Peso Molecular , Óxido Nítrico Sintase Tipo III/metabolismo , Oligossacarídeos/isolamento & purificação , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos
11.
Nat Commun ; 10(1): 1914, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015473

RESUMO

Degradation of extracellular matrix (ECM) underlies loss of cartilage tissue in osteoarthritis, a common disease for which no effective disease-modifying therapy currently exists. Here we describe BNTA, a small molecule with ECM modulatory properties. BNTA promotes generation of ECM components in cultured chondrocytes isolated from individuals with osteoarthritis. In human osteoarthritic cartilage explants, BNTA treatment stimulates expression of ECM components while suppressing inflammatory mediators. Intra-articular injection of BNTA delays the disease progression in a trauma-induced rat model of osteoarthritis. Furthermore, we identify superoxide dismutase 3 (SOD3) as a mediator of BNTA activity. BNTA induces SOD3 expression and superoxide anion elimination in osteoarthritic chondrocyte culture, and ectopic SOD3 expression recapitulates the effect of BNTA on ECM biosynthesis. These observations identify SOD3 as a relevant drug target, and BNTA as a potential therapeutic agent in osteoarthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Benzamidas/farmacologia , Cartilagem Articular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Depuradores de Radicais Livres/farmacologia , Fatores Imunológicos/farmacologia , Osteoartrite/tratamento farmacológico , Sulfonamidas/farmacologia , Animais , Cartilagem Articular/imunologia , Cartilagem Articular/patologia , Condrócitos/efeitos dos fármacos , Condrócitos/imunologia , Condrócitos/patologia , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/imunologia , Matriz Extracelular/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Injeções Intra-Articulares , Masculino , Osteoartrite/genética , Osteoartrite/imunologia , Osteoartrite/patologia , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo , Transcriptoma/imunologia
12.
J Sci Food Agric ; 99(11): 5112-5121, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30982967

RESUMO

BACKGROUND: Salmon bones, a waste by-product from the salmon industry, were used as a protein hydrolysate source for the production of bioactive peptides. The aim of this work was to evaluate the potential antioxidant and anti-inflammatory properties of salmon bone protein hydrolysate (SBPH). RESULTS: Salmon bones were hydrolyzed by separately using one of four proteases (Alcalase, Favourzyme, Neutrase and papain) at various concentrations (10, 25 and 50 mg mL-1 ), where the SBPH derived from 10 mg mL-1 papain hydrolysis exhibited the highest nitric oxide (NO) radical scavenging activity. After ultrafiltration, the MW < 0.65 kDa fraction showed the strongest NO inhibitory activity and was further fractionated by gel filtration chromatography (G1 and G2 fractions) and reverse-phase high-performance liquid chromatographic fractionation of the G1 fraction, from which the three main peaks (H1, H2 and H3) were found to have a marked NO-inhibitory activity and their peptide sequences were determined. Moreover, the G1 fraction was shown to inhibit both the lipopolysaccharide (LPS)-induced NO production and the LPS-induced inducible NO synthase , interleukin-6, tumor necrosis factor-α and induced NO production and the LPSCOX-2 mRNA levels in RAW 264.7 cells. CONCLUSIONS: Salmon bones from the salmon fisheries and farming industry were utilized by enzymatic hydrolysis for the production of valuable peptides. The results of this study suggested that bioactive peptides derived from salmon bones would be alternative anti-inflammation materials in functional resources. © 2019 Society of Chemical Industry.


Assuntos
Anti-Inflamatórios/farmacologia , Osso e Ossos/química , Proteínas de Peixes/química , Depuradores de Radicais Livres/farmacologia , Hidrolisados de Proteína/farmacologia , Salmão , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Biocatálise , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Hidrólise , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Óxido Nítrico/imunologia , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/imunologia , Peptídeo Hidrolases/química , Peptídeos/química , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Hidrolisados de Proteína/química , Células RAW 264.7
13.
Molecules ; 24(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30979087

RESUMO

The effect of elicitation with jasmonic acids (JA) and yeast extract (YE) on the production of phenolic compounds as well as the antioxidant and anti-inflammatory properties of phenolic extracts of lovage was evaluated. The analysis of phenolic compounds carried out with the UPLC-MS technique indicated that rutin was the dominant flavonoid, while 5-caffeoylquinic acid was the main component in the phenolic acid fraction in the lovage leaves. The application of 10 µM JA increased the content of most of the identified phenolic compounds. The highest antioxidant activities estimated as free radical scavenging activity against ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and reducing power were determined for the sample elicited with 10 µM JA, while this value determined as iron chelating ability was the highest for the 0.1% YE-elicited lovage. The 0.1% and 1% YE elicitation also caused significant elevation of the lipoxygenase (LOX) inhibition ability, while all the concentrations of the tested elicitors significantly improved the ability to inhibit cyclooxygenase 2 (COX2) (best results were detected for the 10 µM JA and 0.1% YE2 sample). Thus, 0.1% yeast extract and 10 µM jasmonic acid proved to be most effective in elevation of the biological activity of lovage.


Assuntos
Anti-Inflamatórios/química , Antioxidantes/química , Levisticum/química , Fenóis/química , Benzotiazóis/química , Cromatografia Líquida de Alta Pressão , Ciclopentanos/química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Humanos , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/farmacologia , Oxilipinas/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Rutina/química , Ácidos Sulfônicos/química , Espectrometria de Massas em Tandem , Leveduras/química
14.
Eur J Appl Physiol ; 119(6): 1419-1429, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31030296

RESUMO

PURPOSE: To evaluate the effect of antioxidant supplementation on intense endurance exercise performance and the physiologic exercise response acutely and in early recovery. METHODS: Well-trained cyclists (n = 11, peak VO2: 69 ± 7 ml/min/kg) completed two identical standardized 20-min warm-up periods (WU-1 and WU-2) prior to two performance tests (PT) with a duration of ~ 4 min representing a qualifying (PT-1) and final race (PT-2) on the same day separated by 90 min. Subjects were supplemented orally with placebo (PLA) and N-acetyl cysteine (NAC; 20 mg/kg) before exercise in a double-blinded crossover design. RESULTS: Mean power during PT-1 did not differ (P = 0.39) between PLA (400 ± 44 W) and NAC (401 ± 44 W) as was the case during PT-2 with similar performance (P = 0.74) between PLA (401 ± 43 W) and NAC (400 ± 42 W). Subjective "readiness" was lowered by prior exhaustive exercise from PT-1 to PT-2 (P = 0.012) in both PLA and NAC. Plasma total antioxidant capacity was not affected by supplementation and prior exhaustive exercise (respective main effects: P = 0.83 and P = 0.19) which also was observed for peak VO2 at ~ 5 L/min (P = 0.84 and P = 0.30). In WU-1 and WU-2, both cycling economy at ~ 20% (P = 0.10 and P = 0.21) and plasma potassium at ~ 5 mmol/L (P = 0.46 and P = 0.26) were unaffected by supplementation and prior exercise. CONCLUSIONS: Athletes executing maximal efforts of a ~ 4-min duration twice daily, as seen in track cycling, appear to gain no benefit from oral NAC supplementation on acute and subsequent performance following short-term recovery. Moreover, well-trained cyclists exhibit rapid recovery from a single bout of intense endurance cycling.


Assuntos
Acetilcisteína/farmacologia , Ciclismo/fisiologia , Depuradores de Radicais Livres/farmacologia , Resistência Física/efeitos dos fármacos , Acetilcisteína/administração & dosagem , Adulto , Depuradores de Radicais Livres/administração & dosagem , Humanos , Masculino
15.
Molecules ; 24(8)2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31018491

RESUMO

This study aimed to investigate the antioxidant activity and release behavior of anthocyanin (ANC) loaded within FA-g-MD wall (ANC-FA-g-MD microcapsule) in vitro. The microencapsulation of ANC was prepared by spray drying and displayed a biphasic release profile. The combination of ANC and FA-g-MD (0.0625-1 mg/mL) showed a higher antioxidant activity than that of both individuals. A possible intermolecular interaction between ANC and FA-g-MD was studied by UV-vis spectra. Intracellular reactive oxygen species (ROS), 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, and protein expression of quinone oxidoreductase 1(NQO1), glutathione reductase (GSR) and γ-glutamate cysteine ligase catalytic subunit (γ-GCLC) were measured through human colon cancer cells (HT-29). After a 24-hour incubation of the HT-29, the combinations (0-60 µg/mL) exhibited a high potential to diminish the ROS level. And the distinct upregulated expressions of GCLC and NQO1 of HT-29 were detected after treatment with combinations compared to those of single ones. These results suggested that the ANC-FA-g-MD microcapsules exerts enhanced antioxidant effect with capability of the modulation of GCLC and NQO1.


Assuntos
Antocianinas/farmacologia , Cápsulas/síntese química , Ácidos Cumáricos/química , Portadores de Fármacos , Depuradores de Radicais Livres/farmacologia , Peróxido de Hidrogênio/antagonistas & inibidores , Polissacarídeos/química , Antocianinas/química , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos/métodos , Ativação Enzimática/efeitos dos fármacos , Depuradores de Radicais Livres/química , Regulação da Expressão Gênica , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa Redutase/genética , Glutationa Redutase/metabolismo , Células HT29 , Humanos , Peróxido de Hidrogênio/farmacologia , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Subunidades Proteicas/agonistas , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo
16.
IET Nanobiotechnol ; 13(1): 23-29, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30964033

RESUMO

The stress conditions imposed by the impact of metal and non-metal oxide nanoparticles over plant systems enhances the synthesis of reactive oxygen species (ROS), resulting in oxidative damage at cellular level. The objective of this study was to synthesise the gold nanoparticles (GNps) from the leaves protein of Nicotiana tabacum L. cv. xanthi, its characterisation, and response on plant physiology and ROS scavenging activity on plants after exposure to different stresses. The authors have treated N. tabacum L. cv. xanthi plants with 100, 200, 300, 400, and 500 ppm biochemically synthesised GNps and examined physiological as well as biochemical changes. Results showed that biochemically synthesised GNps exposure significantly increased the seed germination (P < 0.001), root (P < 0.001), shoot growth (P < 0.001), and antioxidant ability (P < 0.05) of plants depending on bioengineered GNPs concentrations. Low concentrations (200-300 ppm) of GNps boosted growth by ∼50% and significantly increase in photosynthetic parameters such as total chlorophyll content (P < 0.05), membrane ion leakage (P < 0.05) as well as malondialdehyde (P < 0.05) content with respect to untreated plants under stress conditions. The high concentration (400-500 ppm) of GNps affected these parameters in a negative manner. The total antioxidant activity was also elevated in the exposed plants in a dose-dependent manner.


Assuntos
Depuradores de Radicais Livres/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Estresse Fisiológico/efeitos dos fármacos , Tabaco/metabolismo , Química Verde , Folhas de Planta/química , Folhas de Planta/metabolismo , Plantas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Tabaco/química
17.
Transfusion ; 59(S2): 1568-1577, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30980740

RESUMO

BACKGROUND: We set out to define the impact of collection, processing, and storage on plasma product microparticle (MP) abundance, potential for nitric oxide (NO) scavenging, and vasoactivity. STUDY DESIGN AND METHODS: Three currently US licensed products were tested: liquid plasma (LP), fresh frozen plasma (FFP), and solvent detergent plasma (SDP), along with a product under development, spray-dried solvent detergent plasma (SD-SDP) with/without beads. Vasoactivity was assessed in vitro using rabbit aortic vascular rings; MP abundance was determined by flow cytometry; and NO scavenging capacity/rate was determined using a biochemical NO consumption assay. All samples were analyzed unprocessed and following centrifugation at two speeds (2,500× g to remove platelets, and 25,000× g to remove microparticles). RESULTS: Significant differences in vasoactivity were observed, with SD-SDP minus beads demonstrating the greatest constriction and FFP the lowest constriction response. All products exhibited the same total NO scavenging capacity; however, significant differences were observed in the maximal rate of scavenging, with SD-SDP minus beads and FFP reacting fastest and SDP the slowest. Across all products, platelet and microparticle depletion had no effect on vasoactivity or NO scavenging (total or rate). Microparticles (RBC derived) were found only in FFP and LP, with relative abundance (LP > FFP). Additionally, storage had no effect on total or RBC-derived MP abundance, NO scavenging, or vasoactivity. CONCLUSION: Although vasoactivity differed between plasma products, we did not find similar differences in either total or RBC-derived MP abundance or NO scavenging capacity/rate.


Assuntos
Aorta/metabolismo , Preservação de Sangue , Micropartículas Derivadas de Células/química , Eritrócitos/química , Depuradores de Radicais Livres , Plasma/química , Vasoconstritores , Animais , Aorta/fisiopatologia , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Humanos , Óxido Nítrico/metabolismo , Coelhos , Vasoconstritores/química , Vasoconstritores/farmacologia
18.
Artif Cells Nanomed Biotechnol ; 47(1): 1122-1131, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30942629

RESUMO

Clinically, available synthetic chemotherapeutics in the treatment for leishmaniasis are associated with serious complications, such as toxicity and emergence of resistance. Natural products from plants can provide better remedies against the Leishmania parasite and can possibly minimize the associated side effects. In this study, various extracts of the callus cultures of Artimisia scoparia established in response to different plant growth regulators (PGRs) were evaluated for their anti-leishmanial effects against Leishmania tropica promastigotes, followed by an investigation of the possible mechanism of action through reactive apoptosis assay using fluorescent microscopy. Amongst the different callus extracts, higher anti-leishmanial activity (IC50:19.13 µg/mL) was observed in the callus raised in-vitro in the presence of 6-Benzylaminopurine (BA) plus 2,4-Dichlorophenoxyacetic Acid (2,4-D) at the concentration of 1.5 mg/L, each. Further, the results of apoptosis assay showed a large number of early-stage apoptotic (EA) and late-stage apoptotic (LA) cells in the Leishmania under the effect of callus extract grown in-vitro at BA plus 2,4-D. For the determination of the potent natural products in the callus extracts responsible for the anti-leishmanial activity, extracts were subjected to Gas chromatography-mass spectrometry (GC-MS) for the metabolite analysis. Nonetheless, higher levels of the metabolites, such as nerolidol (22%), pelletierine (18%), aspidin (15%) and ascaridole (11%) were detected in the callus grown in vitro at BA plus 2,4-D (1.5 mg/L, each). This protocol determines a novel method of production of anti-leishmanial natural products through callus cultures of A. scoparia, a medicinal plant.


Assuntos
Artemisia/crescimento & desenvolvimento , Artemisia/metabolismo , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Leishmania tropica/efeitos dos fármacos , Extratos Vegetais/biossíntese , Extratos Vegetais/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antiprotozoários/química , Antiprotozoários/metabolismo , Antiprotozoários/farmacologia , Apoptose/efeitos dos fármacos , Produtos Biológicos/química , Linhagem Celular , Flavonoides/análise , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Leishmania tropica/citologia , Extratos Vegetais/química , Polifenóis/análise
19.
Food Chem ; 289: 568-574, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30955650

RESUMO

In this work, a facile approach was developed to synthesized alcalase-inorganic hybrid nanocomposite (alcalase@CaHPO4) by immobilizing alcalase with calcium hydrogen phosphate (CaHPO4). The nanocomposite possessed flower-like morphological features with excellent hydrolysis activity on soybean protein isolates (SPI) with 1.57 fold higher compared to free alcalase. The experiment was evident of alcalase@CaHPO4 hybrid nanoflowers with 90% sustainability after the seven cycles of reusability and 80-100% relative activity at 50-70 °C and with 65% at pH 4 in acidic condition. Soybean protein hydrolysates (SPHs) produced by immobilized alcalase possessed 70% radical-scavenging capacity at 0.8 mg/mL concentration and 20% calcium-binding capacity at pH 6. The solubility of SPHs produced by alcalase@CaHPO4 hybrid nanoflowers was also improved by 15% compared to free alcalase. The high radical scavenging capability, good calcium binding capacity and improved solubility of SPHs prepared through alcalase@CaHPO4 hybrid nanoflowers would be highly promising in food industries.


Assuntos
Nanoestruturas/química , Hidrolisados de Proteína/química , Proteínas de Soja/isolamento & purificação , Subtilisinas/química , Cálcio/metabolismo , Fosfatos de Cálcio/química , Enzimas Imobilizadas/química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/farmacologia , Concentração de Íons de Hidrogênio , Hidrólise , Hidrolisados de Proteína/farmacologia , Solubilidade , Proteínas de Soja/química , Soja/química
20.
Mar Drugs ; 17(4)2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30974812

RESUMO

Chitosanase has attracted great attention due to its potential applications in medicine, agriculture, and nutraceuticals. In this study, P. mucilaginosus TKU032, a bacterial strain isolated from Taiwanese soil, exhibited the highest chitosanase activity (0.53 U/mL) on medium containing shrimp heads as the sole carbon and nitrogen (C/N) source. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, a chitosanase isolated from P. mucilaginosus TKU032 cultured on shrimp head medium was determined at approximately 59 kDa. The characterized chitosanase showed interesting properties with optimal temperature and thermal stability up to 70 °C. Three chitosan oligosaccharide (COS) fractions were isolated from hydrolyzed colloidal chitosan that was catalyzed by TKU032 chitosanase. Of these, fraction I showed the highest α-glucosidase inhibitor (aGI) activity (65.86% at 20 mg/mL); its inhibitory mechanism followed the mixed noncompetitive inhibition model. Fractions II and III exhibited strong 2,2-diphenyl1-picrylhydrazyl (DPPH) radical scavenging activity (79.00% at 12 mg/mL and 73.29% at 16 mg/mL, respectively). In summary, the COS fractions obtained by hydrolyzing colloidal chitosan with TKU032 chitosanase may have potential use in medical or nutraceutical fields due to their aGI and antioxidant activities.


Assuntos
Proteínas de Bactérias/isolamento & purificação , Fatores Biológicos/biossíntese , Glicosídeo Hidrolases/isolamento & purificação , Oligossacarídeos/biossíntese , Paenibacillus/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Biocatálise , Fatores Biológicos/farmacologia , Quitosana/metabolismo , Crustáceos/química , Ensaios Enzimáticos/métodos , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Proteínas Fúngicas/metabolismo , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeo Hidrolases/metabolismo , Temperatura Alta , Oligossacarídeos/farmacologia , Paenibacillus/isolamento & purificação , Estabilidade Proteica , Microbiologia do Solo , Especificidade por Substrato , alfa-Glucosidases/metabolismo
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