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1.
J Agric Food Chem ; 67(39): 10921-10929, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31496242

RESUMO

Free amino residues react with α-dicarbonyl compounds (DCs) contributing to the formation of advanced glycation end products (AGEs). Phenolic compounds can scavenge DCs, thus controlling the dietary carbonyl load. This study showed that high-molecular weight cocoa melanoidins (HMW-COM), HMW bread melanoidins (HMW-BM), and especially HMW coffee melanoidins (HMW-CM) are effective DC scavengers. HMW-CM (1 mg/mL) scavenged more than 40% DCs within 2 h under simulated physiological conditions, suggesting some physiological relevance. Partial acid hydrolysis of HMW-CM decreased the dicarbonyl trapping capacity, demonstrating that the ability to react with glyoxal, methylglyoxal (MGO), and diacetyl was mainly because of polyphenols bound to macromolecules. Caffeic acid (CA) and 3-caffeoylquinic acid showed a DC-scavenging kinetic profile similar to that of HMW-CM, while mass spectrometry data confirmed that hydroxyalkylation and aromatic substitution reactions led to the formation of a stable adduct between CA and MGO. These findings corroborated the idea that antioxidant-rich indigestible materials could limit carbonyl stress and AGE formation across the gastrointestinal tract.


Assuntos
Pão/análise , Cacau/química , Café/química , Diacetil/química , Depuradores de Radicais Livres/química , Extratos Vegetais/química , Polímeros/química , Cacau/metabolismo , Café/metabolismo , Diacetil/metabolismo , Depuradores de Radicais Livres/metabolismo , Trato Gastrointestinal/metabolismo , Glioxal/química , Humanos , Modelos Biológicos , Extratos Vegetais/metabolismo , Polímeros/metabolismo , Aldeído Pirúvico/química , Aldeído Pirúvico/metabolismo
2.
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
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.
IET Nanobiotechnol ; 13(2): 134-143, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31051443

RESUMO

This work explores the rapid synthesis of silver nanoparticles (AgNPs) from Musa paradisiaca (M. paradisiaca) bract extract. The bio-reduction of Ag+ ion was recorded using ultraviolet-visible spectroscopy by a surface plasmon resonance extinction peak with an absorbance at 420 nm. The phytoconstituents responsible for the reduction of AgNPs was probed using Fourier transform infrared spectroscopy. The X-ray diffraction pattern confirmed the formation of crystalline AgNPs that were analogous to selected area electron diffraction patterns. Morphological studies showed that the obtained AgNPs were monodispersed with an average size of 15 nm. The biologically synthesised AgNPs showed higher obstruction against tested phytopathogens. The synthesised AgNPs exhibited higher inhibitory zone against fungal pathogen Alternaria alternata and bacterial pathogen Pseudomonas syringae. Free radical scavenging potential of AgNPs was investigated using 1,1-diphenyl-2-picryl hydroxyl and 2,2-azinobis (3-ethylbenzothiazoline)-6-sulphonic acid assays which revealed that the synthesised AgNPs act as a potent radical scavenger. The catalytic efficiency of the synthesised AgNPs was investigated for azo dyes, methyl orange (MO), methylene blue (MB) and reduction of o-nitrophenol to o-aminophenol. The results portrayed that AgNPs act as an effective nanocatalyst to degrade MO to hydrazine derivatives, MB to leucomethylene blue, and o-nitro phenol to o-amino phenol.


Assuntos
Anti-Infecciosos/química , Depuradores de Radicais Livres/química , Nanopartículas Metálicas/química , Musa/química , Extratos Vegetais/metabolismo , Prata/química , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Compostos Azo/análise , Compostos Azo/metabolismo , Bactérias/efeitos dos fármacos , Compostos de Bifenilo/análise , Compostos de Bifenilo/metabolismo , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Fungos/efeitos dos fármacos , Química Verde , Picratos/análise , Picratos/metabolismo , Extratos Vegetais/química , Prata/metabolismo
5.
Plant Cell Rep ; 38(9): 1109-1125, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31134348

RESUMO

KEY MESSAGE: BdASR4 expression was up-regulated during abiotic stress and hormone treatments. Plants over-expressing BdASR4 improved drought tolerant. BdASR4 may regulate antioxidant activities and transcript levels of stress-related and abscisic acid-responsive genes. Abiotic stress conditions negatively affect plant growth and developmental processes, causing a reduction in crop productivity. The abscisic acid-, stress-, ripening-induced (ASR) proteins play important roles in the protection of plants from abiotic stress. Brachypodium distachyon L. is a well-studied monocot model plant. However, ASR proteins of Brachypodium have not been widely studied. In this study, five ASR genes of Brachypodium plant were cloned and characterized. The BdASR genes were expressed in response to various abiotic stresses and hormones. In particular, BdASR4 was shown to encode a protein containing a nuclear localization signal in its C-terminal region, which enabled protein localization in the nucleus. To further examine functions of BdASR4, transgenic Brachypodium plants harboring BdASR4 were generated. Over-expression of BdASR4 was associated with strong drought tolerance, and plants over-expressing BdASR4 preserved more water and displayed higher antioxidant enzyme activities than did the wild-type plants. The transcript levels of stress-responsive genes, reactive oxygen species scavenger-associated genes, and abscisic acid-responsive genes tended to be higher in transgenic plants than in WT plants. Moreover, plants over-expressing BdASR4 were hypersensitive to exogenous abscisic acid at the germination stage. Taken together, these findings suggest multiple roles for BdASR4 in the plant response to drought stress by regulating antioxidant enzymes and the transcription of stress- and abscisic acid-responsive genes.


Assuntos
Antioxidantes/metabolismo , Brachypodium/genética , Proteínas de Plantas/metabolismo , Água/fisiologia , Brachypodium/fisiologia , Núcleo Celular/metabolismo , Secas , Depuradores de Radicais Livres/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico
6.
Plant Cell Rep ; 38(9): 1039-1051, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31144112

RESUMO

KEY MESSAGE: Overexpression of FvC5SD improves drought tolerance in soybean. Drought stress is one of the most important abiotic stress factors that influence soybean crop quality and yield. Therefore, the creation of drought-tolerant soybean germplasm resources through genetic engineering technology is effective in alleviating drought stress. FvC5SD is a type of C-5 sterol desaturase gene that is obtained from the edible fungus Flammulina velutipes. This gene has good tolerance to the effects of stresses, including drought and low temperature, in yeast cells and tomato. In this study, we introduced the FvC5SD gene into the soybean variety Shennong9 through the Agrobacterium-mediated transformation of soybean to identify drought-tolerant transgenic soybean varieties. PCR, RT-PCR, and Southern blot analysis results showed that T-DNA was inserted into the soybean genome and stably inherited by the progeny. The ectopic expression of FvC5SD under the control of a CaMV 35S promoter in transgenic soybean plants enhanced the plant's tolerance to dehydration and drought. Under drought conditions, the transgenic plants accumulated lower levels of reactive oxygen species and exhibited higher activities and expression levels of enzymes and cell than wild-type soybean. iTRAQ analysis of the comparative proteomics showed that some exogenous genes coding either functional or regulatory proteins were induced in the transgenic lines under drought stress. FvC5SD overexpression can serve as a direct and efficient target in improving drought tolerance in soybean and may be an important biotechnological strategy for trait improvement in soybean and other crops.


Assuntos
Flammulina/genética , Depuradores de Radicais Livres/metabolismo , Regulação da Expressão Gênica de Plantas , Oxirredutases/genética , Espécies Reativas de Oxigênio/metabolismo , Secas , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Expressão Gênica , Oxirredutases/metabolismo , Plantas Geneticamente Modificadas , Soja/genética , Estresse Fisiológico , Transgenes
7.
Carbohydr Polym ; 216: 369-375, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047079

RESUMO

Lignocellulosic-like materials are potentially low-cost fermentation substrates, but their pretreatment brings about by-products. This work investigated the effects of furfural on xanthan gum (XG) production, and product quality was evaluated by structure, viscosity and antioxidant capacities. Xanthomonas campestris maintained steady polysaccharide yield (above 13 g·L-1) with enhanced cell growth at low furfural concentrations (below 3.2 g·L-1). The products were verified as XG by FT-IR, XRD, NMR and monosaccharide analysis. Moreover, they were found to have reduced acetyl, rising pyruvate and up-to-down glucuronic acid groups as increasing furfural concentration. Furthermore, XG product with 1 g·L-1 furfural addition showed the best hydroxyl scavenging effects, though reducing powers presented no variation. It was demonstrated that furfural, the common hydrolysis by-product, was not necessarily an inhibitor for fermentation, and an appropriate amount of furfural was beneficial to XG production with steady yield and good quality.


Assuntos
Depuradores de Radicais Livres/metabolismo , Furaldeído/farmacologia , Polissacarídeos Bacterianos/biossíntese , Polissacarídeos Bacterianos/química , Xanthomonas campestris/metabolismo , Fermentação/efeitos dos fármacos , Depuradores de Radicais Livres/química , Radical Hidroxila/química , Viscosidade , Xanthomonas campestris/efeitos dos fármacos
8.
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
9.
J Plant Physiol ; 236: 88-95, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30939333

RESUMO

Enhanced ultraviolet radiation (UV) is an important environmental factor that may cause reductions in the growth and productivity of plants. In the present work we studied the response to UV-B radiation in leaves of the model legume Lotus japonicus. After UV-B treatment, induction of phenyalanine-ammonia lyase gene expression and enzyme activity was detected. Among the ten genes encoding for PAL found in the L. japonicus genome, LjPAL1 was both the most expressed and the most induced. All the genes encoding for enzymes of the isoflavonoid pathway were also strongly induced; this was paralleled by a marked accumulation of vestitol and isoliquiritigenin. Moreover, accumulation of several other isoflavonoids was also detected. In vitro measurements of the free radical scavenging capacity of vestitol indicated that this compound can be an appropriate free radical scavenger, suggesting a possible role for this molecule in the response to abiotic stress. On the other hand, an increase of flavonol levels was not observed while the expression of the key enzymes for flavonol biosynthesis flavanone-3-hydroxylase and flavonol synthase was decreased. Taken together, these results indicate that L. japonicus follows a peculiar strategy in its response to UV radiation by accumulating isoflavonoids as an possible alternative to accumulation of flavonols as observed in other plant species.


Assuntos
Isoflavonas/biossíntese , Lotus/efeitos da radiação , Cromatografia Líquida de Alta Pressão , Indução Enzimática/efeitos da radiação , Depuradores de Radicais Livres/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Lotus/metabolismo , Espectrometria de Massas , Fenilalanina Amônia-Liase/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Reação em Cadeia da Polimerase em Tempo Real , Raios Ultravioleta
10.
Int J Med Mushrooms ; 21(4): 367-380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002632

RESUMO

This study investigates the hepatoprotective effect of a water-alcohol extract of the medicinal mushroom Phellinus caryophylli (Racib.) G. Cunn. (PCE) against acetaminophen (APAP)-induced hepatotoxicity in Swiss albino mice. The mice orally received APAP (150 mg/kg body weight), followed by PCE extract (250 or 500 mg/kg body weight). The liver damage induced by APAP was analyzed on the basis of blood serum parameters (glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, and alkaline phosphatase), antioxidant assays (reduced glutathione and glutathione peroxidase), and tissue peroxidation based on malondialdehyde level. The molecular mechanism underlying the prevention of APAP-induced damage by PCE was also analyzed. Liver damage was confirmed on the basis of increased serum parameter values, decreased antioxidant levels, and cellular and molecular alterations, which PCE restored in a dose-dependent manner. At a transcriptional level, PCE downregulated expression of the preapoptototic gene Bax and the inflammatory gene Cox2 but upregulated the antiapoptotic gene Bcl2 in the mice that received APAP. PCE exerted a hepatoprotective effect by preventing apoptotic and inflammatory events caused by APAP. Thus, this study demonstrates a hepatoprotective effect of PCE, which could be explored further for managing hepatopathy.


Assuntos
Antioxidantes/farmacologia , Artocarpus/microbiologia , Basidiomycota/química , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Acetaminofen/efeitos adversos , Alanina Transaminase/metabolismo , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Modelos Animais de Doenças , Etanol , Depuradores de Radicais Livres/metabolismo , Glutationa Peroxidase/metabolismo , Índia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Camundongos , Óxido Nítrico/metabolismo , Água
11.
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
12.
PLoS Genet ; 15(3): e1008053, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30883543

RESUMO

Eukaryotic striatin forms striatin-interacting phosphatase and kinase (STRIPAK) complexes that control many cellular processes including development, cellular transport, signal transduction, stem cell differentiation and cardiac functions. However, detailed knowledge of complex assembly and its roles in stress responses are currently poorly understood. Here, we discovered six striatin (StrA) interacting proteins (Sips), which form a heptameric complex in the filamentous fungus Aspergillus nidulans. The complex consists of the striatin scaffold StrA, the Mob3-type kinase coactivator SipA, the SIKE-like protein SipB, the STRIP1/2 homolog SipC, the SLMAP-related protein SipD and the catalytic and regulatory phosphatase 2A subunits SipE (PpgA), and SipF, respectively. Single and double deletions of the complex components result in loss of multicellular light-dependent fungal development, secondary metabolite production (e.g. mycotoxin Sterigmatocystin) and reduced stress responses. sipA (Mob3) deletion is epistatic to strA deletion by supressing all the defects caused by the lack of striatin. The STRIPAK complex, which is established during vegetative growth and maintained during the early hours of light and dark development, is mainly formed on the nuclear envelope in the presence of the scaffold StrA. The loss of the scaffold revealed three STRIPAK subcomplexes: (I) SipA only interacts with StrA, (II) SipB-SipD is found as a heterodimer, (III) SipC, SipE and SipF exist as a heterotrimeric complex. The STRIPAK complex is required for proper expression of the heterotrimeric VeA-VelB-LaeA complex which coordinates fungal development and secondary metabolism. Furthermore, the STRIPAK complex modulates two important MAPK pathways by promoting phosphorylation of MpkB and restricting nuclear shuttling of MpkC in the absence of stress conditions. SipB in A. nidulans is similar to human suppressor of IKK-ε(SIKE) protein which supresses antiviral responses in mammals, while velvet family proteins show strong similarity to mammalian proinflammatory NF-KB proteins. The presence of these proteins in A. nidulans further strengthens the hypothesis that mammals and fungi use similar proteins for their immune response and secondary metabolite production, respectively.


Assuntos
Aspergillus nidulans/metabolismo , Proteínas Fúngicas/metabolismo , Aspergillus nidulans/genética , Aspergillus nidulans/crescimento & desenvolvimento , Depuradores de Radicais Livres/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Deleção de Genes , Genes Fúngicos , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Luz , Sistema de Sinalização das MAP Quinases , Modelos Biológicos , Membrana Nuclear/metabolismo , Estrutura Quaternária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Estresse Fisiológico
13.
Biomed Res Int ; 2019: 6951927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30868071

RESUMO

Secondary bioactive compounds of endophytes are inevitable biomolecules of therapeutical importance. In the present study, secondary metabolites profiling of an endophytic bacterial strain, Acinetobacter baumannii, were explored using GC-MS study. Presence of antioxidant substances and antioxidant properties in chloroform (CHL), diethyl ether (DEE), and ethyl acetate (EA) crude extracts of the endophytic bacteria were studied. Total phenolic content (TPC), total flavonoid content (TFC), total antioxidant capacity (TAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and ferrous ion chelating assay were evaluated. A total of 74 compounds were identified from the GC-MS analysis of the EA extract representing mostly alkane compounds followed by phenols, carboxylic acids, aromatic heterocyclic compounds, ketones, aromatic esters, aromatic benzenes, and alkenes. Among the two phenolic compounds, namely, phenol, 2,4-bis(1,1-dimethylethyl)- and phenol, 3,5-bis(1,1-dimethylethyl)-, the former was found in abundance (11.56%) while the latter was found in smaller quantity (0.14%). Moreover, the endophytic bacteria was found to possess a number of metal ions including Fe(II) and Cu(II) as 1307.13 ± 2.35 ppb and 42.38 ± 0.352 ppb, respectively. The extracts exhibited concentration dependent antioxidant and prooxidant properties at high and low concentrations, respectively. The presence of phenolic compounds and metal ions was believed to play an important role in the antioxidant and prooxidant potentials of the extracts. Further studies are suggested for exploring the untapped resource of endophytic bacteria for the development of novel therapeutic agents.


Assuntos
Acinetobacter baumannii/metabolismo , Antioxidantes/metabolismo , Capsicum/metabolismo , Folhas de Planta/metabolismo , Antioxidantes/química , Capsicum/crescimento & desenvolvimento , Capsicum/microbiologia , Flavonoides/química , Flavonoides/metabolismo , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Fenóis/química , Fenóis/metabolismo , Extratos Vegetais/química , Extratos Vegetais/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/microbiologia , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Metabolismo Secundário/genética
14.
Plant Physiol Biochem ; 138: 91-99, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30856415

RESUMO

Traditionally, methylglyoxal (MG) was looked upon as a toxic byproduct of cellular metabolism. Nowadays, MG has been found to be a novel signaling molecule. However, whether MG can trigger the heat tolerance in maize seedlings and the underlying mechanisms is still elusive. In this study, the maize seedlings irrigated with MG increased the survival percentage of seedlings under heat stress (HS), remitted a decrease in tissue vitality and an increase in electrolyte leakage, and reduced membrane lipid peroxidation, implying MG could trigger the heat tolerance of maize seedlings. The further experiments showed that MG drove the ascorbic acid (AsA)-glutathione (GSH) cycle by activating enzymes (glutathione reductase, monodehydroascorbate reductase, dehydroascorbate reductase, and ascorbate peroxidase) and increasing the contents of antioxidants (AsA and GSH) and the ratio of GSH/(GSH + oxidized glutathione) and AsA/(AsA + dehydroascorbate) under both non-HS and HS. Also, the reactive oxygen species (ROS)-scavenger system (catalase, guaiacol peroxidase, carotenoid, total phenols, and flavonoids) and MG-scavenger system (glyoxalase I and glyoxalas II) also were up-regulated in maize seedlings pretreated with MG under non-HS and HS. This work for the first time reported that MG could trigger the heat tolerance of maize seedlings by driving the AsA-GSH cycle and ROS-/MG-scavenging system.


Assuntos
Ácido Ascórbico/metabolismo , Depuradores de Radicais Livres/metabolismo , Glutationa/metabolismo , Aldeído Pirúvico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Plântula/metabolismo , Termotolerância , Zea mays/metabolismo , Temperatura Alta , Peroxidação de Lipídeos , Lipídeos de Membrana/metabolismo
15.
Comput Biol Chem ; 80: 54-65, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901601

RESUMO

Development of novel, safe and effective drug candidates combating the emerging drug resistance has remained a major focus in the mainstream of anti-tuberculosis research. Here, we inspired to design and synthesize series of new pyridin-4-yl-1,3,4-oxadiazol-2-yl-thio-ethylidene-hydrazinecarbothioamide derivatives as potential anti-tubercular agents. The anti-tubercular bioactive assay demonstrated that the synthesized compounds exhibit potent anti-tubercular activity (MIC = 3.9-7.81 µg/mL) in comparison with reference drugs Rifampicin and Isoniazid.We employed pharmacophore probing approach for the identification of CYP51 as a possible drug target for the synthesized compounds. To understand the preferable binding mode, the synthesized molecules were docked onto the active site of Sterol 14 α-demethylases (CYP51) target. From the binding free energy of the docking results it was revealed that the compounds were effective CYP51 inhibitors and acts as antitubercular agent.


Assuntos
Antituberculosos/farmacologia , Oxidiazóis/farmacologia , Piridinas/farmacologia , Tiossemicarbazonas/farmacologia , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/metabolismo , Domínio Catalítico , Família 51 do Citocromo P450/química , Família 51 do Citocromo P450/metabolismo , Desenho de Drogas , Depuradores de Radicais Livres/síntese química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Isoniazida/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Oxidiazóis/síntese química , Oxidiazóis/química , Oxidiazóis/metabolismo , Ligação Proteica , Piridinas/síntese química , Piridinas/química , Piridinas/metabolismo , Rifampina/farmacologia , Relação Estrutura-Atividade , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/química , Tiossemicarbazonas/metabolismo
16.
Int J Biol Macromol ; 128: 761-767, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30726750

RESUMO

The physicochemical characteristics, antioxidant and antitumor activities of partial purified exopolysaccharides from microalgae Chlorella pyrenoidosa FACHB-9, Scenedesmus sp. and Chlorococcum sp. were investigated. The molecular weights were 1.94 × 105, 7.39 × 103 and 3.24 × 104 g/mol, respectively. Monosaccharide analysis indicating that these exopolysaccharides consisted of ten different kinds of sugars and derivatives, respectively. Furthermore, they exhibited obvious free radicals scavenging abilities, which reached to 55.2-71.4% and 63.1-77.5% on DPPH and hydroxyl radicals, respectively. Moreover, the antitumor effects were investigated using human colon cancer cell lines HCT116 and HCT8. The results showed that they had significant antitumor effects considering the inhibitory effects on cell viabilities (17.2-19.2% on HCT116, and 22.9-38.6 on HCT8, respectively), and could decrease the colony amounts (21-42.8% on HCT116, and 11.5-35.2% on HCT8, respectively) at the tested dosage. Thus, these exopolysaccharides may be worth further investigating as effective potential antitumor agents.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/patologia , Depuradores de Radicais Livres/farmacologia , Microalgas/metabolismo , Polissacarídeos/farmacologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Compostos de Bifenilo/química , Sobrevivência Celular/efeitos dos fármacos , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Células HCT116 , Humanos , Radical Hidroxila/química , Peso Molecular , Monossacarídeos/análise , Picratos/química , Polissacarídeos/biossíntese , Polissacarídeos/química
17.
Int J Mol Sci ; 20(4)2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30781644

RESUMO

Oxidative stress is the main pathogenesis of diabetic microangiopathy, which can cause microvascular endothelial cell damage and destroy vascular barrier. In this study, it is found that carnosol protects human microvascular endothelial cells (HMVEC) through antioxidative mechanisms. First, we measured the antioxidant activity of carnosol. We showed that carnosol pretreatment suppressed tert-butyl hydroperoxide (t-BHP)-induced cell viability, affected the production of lactate dehydrogenase (LDH) as well as reactive oxygen species (ROS), and increased the produce of nitric oxide (NO). Additionally, carnosol promotes the protein expression of vascular endothelial cadherin (VE-cadherin) to keep the integrity of intercellular junctions, which indicated that it protected microvascular barrier in oxidative stress. Meanwhile, we investigated that carnosol can interrupt Nrf2-Keap1 protein-protein interaction and stimulated antioxidant-responsive element (ARE)-driven luciferase activity in vitro. Mechanistically, we showed that carnosol promotes the expression of heme oxygenase 1(HO-1) and nuclear factor-erythroid 2 related factor 2(Nrf2). It can also promote the expression of endothelial nitric oxide synthase (eNOS). Collectively, our data support the notion that carnosol is a protective agent in HMVECs and has the potential for therapeutic use in the treatments of microvascular endothelial cell injury.


Assuntos
Antioxidantes/farmacologia , Diterpenos de Abietano/farmacologia , Células Endoteliais/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Antígenos CD/metabolismo , Benzotiazóis/metabolismo , Caderinas/metabolismo , Linhagem Celular , Citoproteção/efeitos dos fármacos , Citoproteção/genética , Diterpenos de Abietano/química , Células Endoteliais/efeitos dos fármacos , Depuradores de Radicais Livres/metabolismo , Humanos , Microvasos/patologia , Simulação de Acoplamento Molecular , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácidos Sulfônicos/metabolismo , terc-Butil Hidroperóxido
18.
Int J Mol Sci ; 20(4)2019 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-30781587

RESUMO

To elucidate the influence of methionine, which is an essential sulfur-containing amino acid, on the antioxidant activity of rice protein (RP), methionine was added to RP (RM). The addition of methionine to RM0.5, RM1.0, RM1.5, RM2.0, and RM2.5 was 0.5-, 1.0-, 1.5-, 2.0-, and 2.5-fold of methionine of RP, respectively. Using the in vitro digestive system, the antioxidant capacities of scavenging free radicals (superoxide; nitric oxide; 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, ABTS), chelating metal (iron), and reducing power were investigated in the hydrolysates of RP and RMs. Upon pepsin-pancreatin digestion, the weakest antioxidant capacity was produced by RP. With the addition of methionine, RMs exhibited more excellent responses to free radical scavenging activities and reducing power than RP, whereas RMs did not produce the marked enhancements in iron chelating activity as compared to RP. The present study demonstrated that RMs differently exerted the free radical scavenging activities that emerged in the protein hydrolysates, in which the strongest scavenging capacities for ABTS, superoxide, and nitric oxide were RM1.5, RM2.0, and RM2.5, respectively. Results suggested that the availability of methionine is a critical factor to augment antioxidant ability of RP in the in vitro gastrointestinal tract.


Assuntos
Antioxidantes/metabolismo , Metionina/metabolismo , Proteínas de Plantas/metabolismo , Proteólise , Antioxidantes/química , Sistema Digestório/metabolismo , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Trato Gastrointestinal/metabolismo , Técnicas In Vitro , Metionina/química , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Oryza/química , Proteínas de Plantas/química , Proteínas de Plantas/farmacologia , Superóxidos/química , Superóxidos/metabolismo
19.
Int Heart J ; 60(2): 392-399, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30745528

RESUMO

Endogenous cardiac regeneration has been focused for decades as a potential therapy for heart diseases with cell loss, and dimethyl sulfoxide (DMSO) has been proposed as a treatment for many diseases. In this study, we aimed to investigate the function of DMSO on fetal cardiomyocyte proliferation. By tracing BrdU+/α actinin+ cells or Ki67+/α actinin+ cells with immunohistochemical staining, we found that DMSO remarkably promoted fetal cardiomyocytes proliferation, and at the late developmental stage (LDS), such effects were more efficient than that at early developmental stage (EDS). Western blot data revealed a significant increase in STAT3 phosphorylation under DMSO treatments at LDS, while not at EDS. Consistently, STAT3 phosphorylation blocker STA21 could greatly reverse DMSO's function at LDS whereas hardly at EDS. Moreover, hearts at the EDS had less total STAT3 protein, but relatively much higher level of phosphorylated STAT3. This suggests that DMSO promote fetal cardiomyocytes proliferation, and STAT3 phosphorylation play a pivotal role in DMSO's function. With maturation, DMSO exerted a better ability to favor cardiomyocyte proliferation depending on STAT3 phosphorylation. Therefore, DMSO could serve as an effective, economic, and safe therapy for heart diseases with cell loss.


Assuntos
Proliferação de Células , Dimetil Sulfóxido , Maturidade dos Órgãos Fetais , Miócitos Cardíacos , Regeneração , Fator de Transcrição STAT3/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/farmacologia , Feminino , Desenvolvimento Fetal/fisiologia , Pesquisa Fetal , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Idade Gestacional , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Fosforilação , Gravidez , Regeneração/efeitos dos fármacos , Regeneração/fisiologia
20.
Gene ; 696: 122-134, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30790651

RESUMO

Mosses are predominant terrestrial vegetation in Antarctica. Their distributions appear to be controlled more by water and salinity. The Antarctic moss Pohlia nutans can tolerate high salt stress. Here, high-throughput sequencing was employed to study the transcriptional characteristics of P. nutans under salt stress. Differentially expressed genes (DEGs) analysis showed that 1340 genes were significantly upregulated and 831 genes were markedly downregulated. The expression of representative DEGs including abscisic acid (ABA) and Jasmonates (JAs) pathway-related genes, antioxidant enzyme genes, and flavonoid biosynthesis-related genes were analyzed by real-time PCR and most were upregulated after salt stress. Furthermore, malondialdehyde (MDA) content was significantly increased after salt treatment. The levels of hydroxyl free radical (∙OH) first rose then quickly decreased. In addition, the activities of antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD), and the flavonoid content were enhanced after salt stress. Exogenous application of ABA, Methyl jasmonate (MeJA) or proanthocyanidins (PA) improved the performance of P. nutans in response to high salt stress. Furthermore, real-time PCR showed that ABA or MeJA treatment upregulated the gene expression of antioxidant and flavonoid biosynthesis-related enzymes. These results suggest that the responses of P. nutans under salt stress are involved in activating phytohormone signaling pathways which trigger two main antioxidant defense systems (i.e., antioxidant enzymes and flavonoids) for protecting cell and scavenging reactive oxygen species.


Assuntos
Briófitas/fisiologia , Depuradores de Radicais Livres/metabolismo , Proteínas de Plantas/metabolismo , Tolerância ao Sal/genética , Transdução de Sinais/genética , Regiões Antárticas , Briófitas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala , Reguladores de Crescimento de Planta/genética , Reguladores de Crescimento de Planta/metabolismo , Proteínas de Plantas/genética , Espécies Reativas de Oxigênio/metabolismo , Sequenciamento Completo do Exoma
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