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1.
Nat Commun ; 11(1): 4951, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009382

RESUMO

Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials.


Assuntos
Antineoplásicos/farmacologia , Espaço Extracelular/metabolismo , Depuradores de Radicais Livres/metabolismo , Morte Celular Imunogênica , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular Tumoral , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Proteína HMGB1/metabolismo , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Polietilenoglicóis/química , Microambiente Tumoral/efeitos dos fármacos
2.
Food Chem Toxicol ; 145: 111701, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32858131

RESUMO

Obesity and its related metabolic disorders, as well as infectious diseases like covid-19, are important health risks nowadays. It was recently documented that long-term fasting improves metabolic health and enhanced the total antioxidant capacity. The present study investigated the influence of a 10-day fasting on markers of the redox status in 109 subjects. Reducing power, 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation(ABTS) radical scavenging capacity, and hydroxyl radical scavenging capacity increased significantly, and indicated an increase of circulating antioxidant levels. No differences were detected in superoxide scavenging capacity, protein carbonyls, and superoxide dismutase when measured at baseline and after 10 days of fasting. These findings were concomitant to a decrease in blood glucose, insulin, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) and triglycerides as well as an increase in total cholesterol/high-density lipoprotein (HDL) ratio. In addition, the well-being index as well as the subjective energy levels increased, documenting a good tolerability. There was an interplay between redox and metabolic parameters since lipid peroxidation baseline levels (thiobarbituric acid reactive substances [TBARS]) affected the ability of long-term fasting to normalize lipid levels. A machine learning model showed that a combination of antioxidant parameters measured at baseline predicted the efficiency of the fasting regimen to decrease LDL levels. In conclusion, it was demonstrated that long-term fasting enhanced the endogenous production of antioxidant molecules, that act protectively against free radicals, and in parallel improved the metabolic health status. Our results suggest that the outcome of long-term fasting strategies could be depending on the baseline values of the antioxidative and metabolic status of subjects.


Assuntos
Jejum/metabolismo , Depuradores de Radicais Livres/metabolismo , Obesidade/dietoterapia , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Peroxidação de Lipídeos/fisiologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adulto Jovem
3.
PLoS One ; 15(8): e0237031, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790698

RESUMO

Tomato is the most widespread vegetable crop in the world. In Italy, tomatoes are mainly cultivated in the South and in the Campania region, precisely in the area called Agro Nocerino-Sarnese. This flatland is affected by an extreme level of environmental degradation, especially related to the Sarno River, where concentrations of Potential Toxic Elements (PTEs) have been found to be higher than the maximum permitted level. The aim of this study was to determine the PTEs uptake by roots and their translocation to the aerial parts of the plants of two cultivars of tomatoes (Pomodoro Giallo and San Marzano Cirio 3). To the purpose, samples of the two cultivars were grown both in pots with experimentally contaminated soil containing: Cr or Cd or Pb at extremely high concentrations and in pots with uncontaminated soils (control). Additionally, the antioxidant properties of the cultivars selected grown on uncontaminated/contaminated soils were assessed. The results showed that Cd was the contaminant that most significantly interfered with the growth of both cultivars of tomato plants, whereas Pb caused lower phenotypical damage. Cd translocation from root to the organs of tomato plants was observed in both cultivars. Specifically, the total amount of Cd found in stems and leaves was higher in the Pomodoro Giallo (254.4 mg/kg dry weight) than in the San Marzano Cirio 3 (165.8 mg/kg dry weight). Cd was the only PTE found in the fruits of both cultivars, with values of 6.1 and 3.9 mg/kg dry weight of Pomodoro Giallo and San Marzano Cirio 3, respectively. The fruits of tomato plants grown in PTEs-contaminated soil showed inhibition or stimulations of the radical scavenging activity compared to the fruits grown in uncontaminated soil. This study highlighted that, despite the relatively high experimental concentrations of PTEs, their translocation to the edible part was comparatively low or absent.


Assuntos
Lycopersicon esculentum/metabolismo , Metais Pesados/farmacocinética , Poluentes do Solo/farmacocinética , Bioacumulação , Transporte Biológico Ativo , Cádmio/farmacocinética , Cádmio/toxicidade , Cromo/farmacocinética , Cromo/toxicidade , Depuradores de Radicais Livres/metabolismo , Radicais Livres/metabolismo , Itália , Chumbo/farmacocinética , Chumbo/toxicidade , Lycopersicon esculentum/efeitos dos fármacos , Lycopersicon esculentum/crescimento & desenvolvimento , Metais Pesados/toxicidade , Poluentes do Solo/toxicidade , Distribuição Tecidual
4.
Nat Commun ; 11(1): 1515, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251291

RESUMO

Hydroxytyrosol is an antioxidant free radical scavenger that is biosynthesized from tyrosine. In metabolic engineering efforts, the use of the mouse tyrosine hydroxylase limits its production. Here, we design an efficient whole-cell catalyst of hydroxytyrosol in Escherichia coli by de-bottlenecking two rate-limiting enzymatic steps. First, we replace the mouse tyrosine hydroxylase by an engineered two-component flavin-dependent monooxygenase HpaBC of E. coli through structure-guided modeling and directed evolution. Next, we elucidate the structure of the Corynebacterium glutamicum VanR regulatory protein complexed with its inducer vanillic acid. By switching its induction specificity from vanillic acid to hydroxytyrosol, VanR is engineered into a hydroxytyrosol biosensor. Then, with this biosensor, we use in vivo-directed evolution to optimize the activity of tyramine oxidase (TYO), the second rate-limiting enzyme in hydroxytyrosol biosynthesis. The final strain reaches a 95% conversion rate of tyrosine. This study demonstrates the effectiveness of sequentially de-bottlenecking rate-limiting steps for whole-cell catalyst development.


Assuntos
Evolução Molecular Direcionada/métodos , Escherichia coli/enzimologia , Depuradores de Radicais Livres/metabolismo , Engenharia Metabólica , Álcool Feniletílico/análogos & derivados , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas Biossensoriais , Vias Biossintéticas/genética , Corynebacterium glutamicum/enzimologia , Corynebacterium glutamicum/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Estudos de Viabilidade , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Mutagênese Sítio-Dirigida , Mutação , Álcool Feniletílico/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tirosina/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Ácido Vanílico/metabolismo
5.
Proc Natl Acad Sci U S A ; 117(12): 6910-6917, 2020 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-32152121

RESUMO

Auxin is a class of plant hormone that plays a crucial role in the life cycle of plants, particularly in the growth response of plants to ever-changing environments. Since the auxin responses are concentration-dependent and higher auxin concentrations might often be inhibitory, the optimal endogenous auxin level must be closely controlled. However, the underlying mechanism governing auxin homeostasis remains largely unknown. In this study, a UDP-glycosyltransferase (UGT76F1) was identified from Arabidopsis thaliana, which participates in the regulation of auxin homeostasis by glucosylation of indole-3-pyruvic acid (IPyA), a major precursor of the auxin indole-3-acetic acid (IAA) biosynthesis, in the formation of IPyA glucose conjugates (IPyA-Glc). In addition, UGT76F1 was found to mediate hypocotyl growth by modulating active auxin levels in a light- and temperature-dependent manner. Moreover, the transcription of UGT76F1 was demonstrated to be directly and negatively regulated by PIF4, which is a key integrator of both light and temperature signaling pathways. This study sheds a light on the trade-off between IAA biosynthesis and IPyA-Glc formation in controlling auxin levels and reveals a regulatory mechanism for plant growth adaptation to environmental changes through glucosylation of IPyA.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Glucose/metabolismo , Hipocótilo/crescimento & desenvolvimento , Ácidos Indolacéticos/farmacologia , Indóis/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Glucosiltransferases/metabolismo , Glicosilação , Hipocótilo/efeitos dos fármacos , Hipocótilo/metabolismo , Hipocótilo/efeitos da radiação , Indóis/química , Luz , Reguladores de Crescimento de Planta/farmacologia , Plântula , Temperatura
6.
Food Chem ; 318: 126484, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32151923

RESUMO

The phytochemical contents, peroxyl radical scavenging capacities (PSCs) and cellular antioxidant activities (CAAs) of free and bound fractions of rice were reported. Black rice had the highest total phenolic content and total flavonoid content in free and bound fractions, followed by red rice, brown rice, and polished rice. Black rice contained much more free phenolic compounds than other rice samples, such as cyanidin-3-O-glucoside, protocatechuic acid, and vanillic acid. Tocopherols and tocotrienols contents were highest in red rice, then in black rice, brown rice, and polished rice. PSCs and CAAs of free and bound fractions were in the order: black rice > red rice > brown rice > polished rice, except that bound CAA of red rice was higher than that of black rice. The cellular uptake rate of free phenolics was highest in red rice, while cellular uptake rates of bound phenolics were highest in brown rice and polished rice.


Assuntos
Antioxidantes/análise , Carcinoma Hepatocelular/tratamento farmacológico , Flavonoides/análise , Neoplasias Hepáticas/tratamento farmacológico , Oryza/química , Fenóis/análise , Compostos Fitoquímicos/análise , Amidinas/efeitos adversos , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Depuradores de Radicais Livres/metabolismo , Células Hep G2 , Humanos , Estresse Oxidativo/efeitos dos fármacos , Peróxidos/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Especificidade da Espécie , Tocoferóis/análise , Tocotrienóis/análise
7.
Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 47-52, Jan.-Mar. 2020. graf
Artigo em Inglês | LILACS | ID: biblio-1090559

RESUMO

Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.


Assuntos
Animais , Masculino , Acetilcisteína/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Cisplatino/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Antineoplásicos/toxicidade , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Microscopia Eletrônica de Varredura , Potenciais Evocados Auditivos do Tronco Encefálico , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Imunofluorescência , Cisplatino/uso terapêutico , Ratos Wistar , Cóclea/anatomia & histologia , Cóclea/efeitos dos fármacos , Radicais Livres , Glutationa Peroxidase/metabolismo , Perda Auditiva Neurossensorial/prevenção & controle
8.
J Trace Elem Med Biol ; 58: 126448, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901726

RESUMO

BACKGROUND: Increasing resistance to available drugs and their associated side-effects have drawn wide attention towards designing alternative therapeutic strategies for control of hyperglycemia and oxidative stress. The roles of the sizes and shapes of the nanomaterials used in the treatment and management of Type 2 Diabetes Mellitus (T2DM) in preventing chronic hyperglycaemia and oxidative stress are investigated. We report specifically on the effects of doping silver (Ag) into the ZnO nanorods (ZnO:Ag NR's) as a rational drug designing strategy. METHODS: Inhibition of porcine pancreatic α-amylase, murine pancreatic amylase, α-glucosidase, murine intestinal glucosidase and amyloglucosidase are checked for evaluation of antidiabetic potential. In addition, the radical scavenging activities of ZnO:Ag NR's against nitric oxide, DDPH and superoxide radicals are evaluated. RESULTS: Quantitative radical scavenging and metabolic enzyme inhibition activities of ZnO:Ag NR's at a concentration of 100 µg/mL were found to depend on the amount of Ag doped in up to a threshold level (3-4 %). Circular dichroism analysis revealed that the interaction of the NR's with the enzymes altered their secondary conformation. This alteration is the underlying mechanism for the potent enzyme inhibition. CONCLUSIONS: Enhanced inhibition of enzymes and scavenging of free radicals primarily responsible for reactive oxygen species (ROS) mediated damage, provide a strong scientific rationale for considering ZnO:Ag NR's as a candidate nanomedicine for controlling postprandial hyperglycaemia and the associated oxidative stress.


Assuntos
Antioxidantes/farmacologia , Hipoglicemiantes/farmacologia , Nanotubos/química , Prata/farmacologia , Óxido de Zinco/farmacologia , Amilases/antagonistas & inibidores , Amilases/metabolismo , Animais , Compostos de Bifenilo/química , Inibidores Enzimáticos/farmacologia , Depuradores de Radicais Livres/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Intestinos/enzimologia , Camundongos , Nanotubos/ultraestrutura , Óxido Nítrico/metabolismo , Pâncreas/enzimologia , Picratos/química , Superóxidos/metabolismo , Suínos , alfa-Glucosidases/metabolismo
9.
Plant Biol (Stuttg) ; 22(3): 472-479, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31990448

RESUMO

Cadmium (Cd) is detrimental to crops and the environment. This work examines the natural mechanisms underlying silicon- (Si-)directed Cd detoxification in rice plants. The addition of Si to plants under Cd stress caused significant improvements in morphological parameters, chlorophyll score, Fv /Fm and total soluble protein concentration compared to controls, confirming that Si is able to ameliorate Cd-induced damage in rice plants. This morpho-physiological evidence was correlated with decreased cell death and electrolyte leakage after Si application. The results showed no critical changes in root Cd concentration, while shoot Cd decreased significantly after Si supplementation in comparison with Cd-stressed rice. Additionally, expression of Cd transporters (OsNRAMP5 and OsHMA2) was significantly down-regulated while the concentration of phytochelatin, cysteine and glutathione, together with expression of OsPCS1 (phytochelatin synthase) in roots of Cd-stressed rice was significantly induced when subjected to Si treatment. This confirms that the alleviation of Cd stress is not only limited to the down-regulation of Cd transporters but also closely related to the phytochelatin-driven vacuolar storage of Cd in rice roots. The enzymatic analysis further revealed the role of SOD and GR enzymes in protecting rice plants from Cd-induced oxidative harm. These findings suggest a mechanistic basis in rice plants for Si-mediated mitigation of Cd stress.


Assuntos
Cádmio , Depuradores de Radicais Livres , Oryza , Fitoquelatinas , Silício , Cádmio/metabolismo , Depuradores de Radicais Livres/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Oryza/química , Oryza/efeitos dos fármacos , Fitoquelatinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Silício/metabolismo , Silício/farmacologia
10.
Carbohydr Polym ; 232: 115802, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952601

RESUMO

A series of biocompatible and non- toxic polysaccharide molecules have been successfully fabricated and explored their potential application for scavenging the carbonyl species in vitro. These macromolecules were dextrans with different hydrazide substitution ratios determined by TNBS assay, NMR and FTIR characterization. The colorimetric assay had demonstrated that these macromolecules could effectively scavenge acrolein, oxidized bovine serum albumin (BSA) in buffer solutions as well as carbonyl proteins from serum. The scavengers could achieve twice more scavenging effects for modified dextrans with high molecular weight (Mw = 100,000) than those of low ones (Mw = 40,000) with the same substitution ratio. Protein gel electrophoresis confirmed that the formation of the complex between carbonyls and modified dextrans resulted in appearance of slower bands. It also revealed that such macromolecules could protect cultured cells against the toxicity of acrolein or its derivatives. The proposed macromolecules indicated a very promising capability as scavengers for oxidative stress plus its derivatives without side effects.


Assuntos
Dextranos/metabolismo , Depuradores de Radicais Livres/metabolismo , Hidrazinas/metabolismo , Soroalbumina Bovina/metabolismo , Animais , Bovinos , Dextranos/química , Depuradores de Radicais Livres/química , Hidrazinas/química , Estrutura Molecular , Carbonilação Proteica , Soroalbumina Bovina/química
11.
Comput Biol Chem ; 84: 107170, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31810852

RESUMO

Octopamine is a neurotransmitter in invertebrates and a phenol analog of norepinephrine. The crystallographic and spectral (UV-visUV, and NMR) characteristics of octopamine were investigated experimentally and theoretically by applying appropriate level of theory, B3LYP-D3BJ/6-311++G(d,p), which reproduced well the experimental bond lengths and angles. The intramolecular interactions governing the stability of conformers were described by NBO and QTAIM analyses. The antiradical potencies of octopamine and norepinephrine towards DPPH and ABTS+ were examined with special emphasis on the preferred mechanism and effect of catechol moiety. Several techniques were used to distinguish Hydrogen Atom Transfer (HAT) and Proton Coupled Electron Transfer (PCET) mechanisms for reaction with DPPH. The calculated rate constants of the reactions with both radicals showed that Sequential Proton Loss Electron Transfer (SPLET) mechanism was dominant both thermodynamically and kinetically, with values of thermodynamic functions and rate constants clearly proving the importance of the second hydroxyl group in structure. The Molecular Docking and afterward Molecular Dynamics calculations of formed complexes between octopamine/norepinephrine with ß1- and ß2- adrenergic receptors examined in details the interactions that lead to the formation of stable complexes. The number of strong interactions of amino acids with norepinephrine was higher, but the absence of hydroxyl group in octopamine did not lead to a significant change in the type of interactions and stability. The formed complexes showed higher flexibility of amino acids, similar compactness of structure as proteins and increased interatomic distances of the backbone when compared to pure proteins.


Assuntos
Depuradores de Radicais Livres/química , Neurotransmissores/química , Norepinefrina/química , Octopamina/química , Animais , Camelídeos Americanos , Depuradores de Radicais Livres/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Neurotransmissores/metabolismo , Norepinefrina/metabolismo , Octopamina/metabolismo , Receptores Adrenérgicos beta 1/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Perus
12.
Int J Mol Sci ; 20(23)2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31801293

RESUMO

The gastric secretory trefoil factor family (TFF) peptides xP1 and xP4 are the Xenopus laevis orthologs of mammalian TFF1 and TFF2, respectively. The aim of this study was to analyze the molecular forms of xP1 and xP4 in the X. laevis gastric mucosa by FPLC. xP1 mainly occurred in a monomeric low-molecular-mass form and only a minor subset is associated with the mucus fraction. The occurrence of monomeric xP1 is unexpected because of its odd number of cysteine residues. Probably a conserved acidic residue flanking Cys55 allows monomeric secretion. Furthermore, Cys55 is probably post-translationally modified. For the first time, we hypothesize that the free thiol of monomeric xP1-and probably also its mammalian ortholog TFF1-could have a protective scavenger function, e.g., for reactive oxygen/nitrogen species. In contrast, xP4 mainly occurs in a high-molecular-mass form and is non-covalently bound to a mucin similarly as TFF2. In vitro binding studies with radioactively labeled porcine TFF2 even showed binding to X. laevis gastric mucin. Thus, xP4 is expected to bind as a lectin to an evolutionary conserved sugar epitope of the X. laevis ortholog of mucin MUC6 creating a tight mucus barrier. Taken together, xP1 and xP4 appear to have different gastric protective functions.


Assuntos
Proteínas de Anfíbios/química , Depuradores de Radicais Livres/química , Mucosa Gástrica/metabolismo , Substâncias Protetoras/química , Processamento de Proteína Pós-Traducional , Fator Trefoil-1/química , Proteínas de Anfíbios/isolamento & purificação , Proteínas de Anfíbios/metabolismo , Proteínas de Anfíbios/farmacologia , Animais , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/metabolismo , Depuradores de Radicais Livres/farmacologia , Peso Molecular , Mucinas/química , Mucinas/metabolismo , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Ligação Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/isolamento & purificação , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacologia , Espécies Reativas de Nitrogênio/antagonistas & inibidores , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Suínos , Fator Trefoil-1/isolamento & purificação , Fator Trefoil-1/metabolismo , Fator Trefoil-1/farmacologia , Xenopus laevis/fisiologia
13.
Molecules ; 24(23)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775226

RESUMO

Brassica vegetables, such as cabbage, have many health benefits arising from their antioxidant and anticancer properties. These properties are endowed by the metabolite composition of the plant, and it is therefore important to elucidate the metabolic profile and associated activities in this genus. This study objectively evaluated the characteristics of cabbage varieties using metabolic profiling to identify the primary metabolic components that correlate with antioxidant activity and taste attributes. GC-MS analysis was used to identify the primary metabolites. Antioxidant activity was measured by oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging assays, and an electronic tongue was used to quantitate nine taste attributes. Orthogonal projections to latent structures (OPLS) using SIMCA 14 correlated the metabolite components with the taste and antioxidant characteristics. We identified 4-aminobutyric acid, fructose 1-phosphate, adipic acid, 5-oxoproline, N-acetylglycine, O-phosphoethanolamine, and homovanillic acid as important determinants of DPPH scavenging activity and umami, sourness, acidic bitterness, irritant and saltiness, bitterness, astringency, and richness, respectively. These metabolites represent markers indicating breed differences and contribute to differential cabbage functionality. These studies could be extended to measure additional metabolites, as well as to understand the role of growth conditions on the metabolic profile and health benefits of plants.


Assuntos
Antioxidantes/metabolismo , Brassica/metabolismo , Metaboloma , Metabolômica , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/química , Brassica/química , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Capacidade de Absorbância de Radicais de Oxigênio , Picratos/química , Extratos Vegetais/química , Paladar
14.
Molecules ; 24(20)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652501

RESUMO

Centaurium erythraea is recommended for the treatment of gastrointestinal disorders and to reduce hypercholesterolemia in ethno-medicinal practice. To perform a top-down study that could give some insight into the molecular basis of these bioactivities, decoctions from C. erythraea leaves were prepared and the compounds were identified by liquid chromatography-high resolution tandem mass spectrometry (LC-MS/MS). Secoiridoids glycosides, like gentiopicroside and sweroside, and several xanthones, such as di-hydroxy-dimethoxyxanthone, were identified. Following some of the bioactivities previously ascribed to C. erythraea, we have studied its antioxidant capacity and the ability to inhibit acetylcholinesterase (AChE) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Significant antioxidant activities were observed, following three assays: free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) reduction; lipoperoxidation; and NO radical scavenging capacity. The AChE and HMGR inhibitory activities for the decoction were also measured (56% at 500 µg/mL and 48% at 10 µg/mL, respectively). Molecular docking studies indicated that xanthones are better AChE inhibitors than gentiopicroside, while this compound exhibits a better shape complementarity with the HMGR active site than xanthones. To the extent of our knowledge, this is the first report on AChE and HMGR activities by C. erythraea decoctions, in a top-down analysis, complemented with in silico molecular docking, which aims to understand, at the molecular level, some of the biological effects ascribed to infusions from this plant.


Assuntos
Antioxidantes/farmacologia , Centaurium/química , Inibidores da Colinesterase/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Extratos Vegetais/química , Xantonas/química , Acetilcolinesterase/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Inibidores da Colinesterase/química , Cromatografia Líquida de Alta Pressão , Depuradores de Radicais Livres/metabolismo , Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Glucosídeos Iridoides/química , Glicosídeos Iridoides/química , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem
15.
Molecules ; 24(20)2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31652513

RESUMO

Halophytic grasses have been recently targeted as possible sources of nutraceutical and medicinal compounds. Nonetheless, few studies have been conducted on the phytochemistry and biological activities of metabolites produced by these plants. Among these, Spartina maritima (Curtis) Fernald, Spartina patens (Aiton.) Muhl., and Puccinellia maritima (Hudson) Parl. are three halophytic grasses whose chemical composition and bioactivities are unknown. The present work broadens the knowledge on the polyphenolic and chlorophyll composition of these species identifying for the first time hydroxycinnamic acids and their derivatives, flavones, flavonols, lignans, as well as chlorophylls and xantophylls. The extracts were particularly rich in caffeic and ferulic acids as well as in trihydroxymethoxyflavone, apigenin and tricin derivatives. Interestingly, several of the identified compounds are relevant from a medicinal and nutraceutical point of view putting in evidence the potential of these species. Thus, the antioxidant, anti-acetylcholinesterase, antibacterial, and antifungal activities of the polyphenolic extracts were assessed as well as the photophysical properties of the chlorophyll-rich extracts. The results, herein presented for the first time, reinforce the nutritional and the medicinal potential of these halophytic grasses.


Assuntos
Clorofila/química , Extratos Vegetais/química , Poaceae/química , Polifenóis/química , Plantas Tolerantes a Sal/química , Acetilcolinesterase/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antioxidantes/metabolismo , Clorofila/análise , Clorofila/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/análise , Ácidos Cumáricos/química , Suplementos Nutricionais , Flavonas/análise , Flavonas/química , Flavonoides/análise , Flavonoides/química , Flavonóis/análise , Flavonóis/química , Depuradores de Radicais Livres/metabolismo , Lignanas/análise , Lignanas/química , Plantas Medicinais/química , Poaceae/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Xantofilas/análise , Xantofilas/química
16.
Colloids Surf B Biointerfaces ; 184: 110508, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31546223

RESUMO

Extensive utilization of silver nanoparticles (AgNP) has raised concerns of their safety profile upon interaction with biological system. In past decade, various nanoparticles (NPs) with excellent antimicrobial potential have been synthesized, a majority of which have struggled with the established toxicity in biological systems. The NPs safety is still a hot debate and various strategies are being adopted to overcome this giant limitation. This paper successfully reports comparative toxicity profiles of previously synthesized antimicrobial NPs in our lab and concludes the effectiveness of biologically synthesized NPs for its safe usage in biological systems. In this study, five of our previously synthesized NPs that showed excellent antimicrobial potential were compared for their in vivo toxicity and corresponding radical scavenging activities. Based on lowest morbidity, mortality, weight loss, toxicity and agglomeration profile, best NPs with highest antimicrobial potentials were screened out and used for further biomedical applications. The previously reported NPs used in this study included Aerva javanica synthesized nanoparticles (AjNPs), Heliotropium crispium synthesized nanoparticles (HcNPs), and violacein capped nanoparticles (VNPs), these showed least toxicity upon in vivo histological analysis. AjNPs among them showed maximum safety and efficacy profile and consistently showed least production of reactive oxygen species, least mortality and morbidity rate as compared to other groups. Present study establishes that all these biologically synthesized NPs and specifically AjNPs can be efficiently employed as antimicrobial agents as they have not exhibited toxic profile and have shown least accumulation into the organs such as liver spleen and kidney.


Assuntos
Antibacterianos/toxicidade , Depuradores de Radicais Livres/toxicidade , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Animais , Antibacterianos/análise , Antibacterianos/metabolismo , Coloides/análise , Coloides/metabolismo , Coloides/toxicidade , Depuradores de Radicais Livres/análise , Depuradores de Radicais Livres/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Nanopartículas Metálicas/análise , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Prata/análise , Prata/metabolismo , Baço/efeitos dos fármacos , Baço/patologia , Propriedades de Superfície
17.
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
18.
J Cosmet Laser Ther ; 21(6): 332-342, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31451001

RESUMO

Objective: The objective of current study to investigate the photo protective potential of synbiotic formulation comprising of prebiotic and probiotic. Methods: Selenium nanoparticles were synthesized by chemical reduction method and investigated for physical-chemical properties including morphology, physical state, and free radical scavenging potential. Selection of probiotic biomass was made on the free radical scavenging potential by using NO assay. A topical w/o emulsion-based cream was prepared with screened ingredients to achieve a stable product with optimum free radical scavenging potential. The finished product was investigated for various mechanical, physiochemical, and viscoelastic characteristics. The SPF of optimized formulation was determined in UV-stimulated Wistar rat model. Results: Results indicated that the finished product shows nanoscale feature of elemental selenium. Cream comprising of potential free radical reagent (Selenium nanoparticles with IC50 50.097 µg/ml and biomass of Lactobacillus rhamnosus have IC50 61.63 µg/ml) exhibits a SPF of 29.77. Optimized skin care formulation has desirable physiochemical and viscoelastic properties required for topical application. Histopathology and Draize test indicated the finished product does not show any sign of skin toxicity. Conclusion: Results inferred that topical formulation combining the features of selenium and probiotic biomass offer an effective alternative for the treatment of sunburn complications.


Assuntos
Queimadura Solar/terapia , Simbióticos/administração & dosagem , Administração Cutânea , Animais , Antioxidantes/administração & dosagem , Emulsões , Depuradores de Radicais Livres/metabolismo , Lactobacillus , Nanopartículas/química , Tamanho da Partícula , Ratos , Ratos Wistar , Selênio/administração & dosagem , Higiene da Pele , Fator de Proteção Solar
19.
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 , Ligação 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
20.
Molecules ; 24(15)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366105

RESUMO

The biological process, 3-O-galactosylation, is important in plant cells. To understand the mechanism of the reduction of flavonol antioxidative activity by 3-O-galactosylation, myricetin-3-O-galactoside (M3OGa) and myricetin aglycone were each incubated with 2 mol α,α-diphenyl-ß-picrylhydrazyl radical (DPPH•) and subsequently comparatively analyzed for radical adduct formation (RAF) products using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS) technology. The analyses revealed that M3OGa afforded an M3OGa-DPPH adduct (m/z 873.1573) and an M3OGa-M3OGa dimer (m/z 958.1620). Similarly, myricetin yielded a myricetin-DPPH adduct (m/z 711.1039) and a myricetin-myricetin dimer (m/z 634.0544). Subsequently, M3OGa and myricetin were compared using three redox-dependent antioxidant analyses, including DPPH•-trapping analysis, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-trapping analysis, and •O2 inhibition analysis. In the three analyses, M3OGa always possessed higher IC50 values than those of myricetin. Conclusively, M3OGa and its myricetin aglycone could trap the free radical via a chain reaction comprising of a propagation step and a termination step. At the propagation step, both M3OGa and myricetin could trap radicals through redox-dependent antioxidant pathways. The 3-O-galactosylation process, however, could limit these pathways; thus, M3OGa is an inferior antioxidant compared to its myricetin aglycone. Nevertheless, 3-O-galactosylation has a negligible effect on the termination step. This 3-O-galactosylation effect has provided novel evidence that the difference in the antioxidative activities of phytophenols exists at the propagation step rather than the termination step.


Assuntos
Flavonoides/química , Depuradores de Radicais Livres/química , Galactosídeos/química , Superóxidos/química , Compostos de Bifenilo/antagonistas & inibidores , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/metabolismo , Dimerização , Flavonoides/metabolismo , Depuradores de Radicais Livres/metabolismo , Radicais Livres , Galactosídeos/metabolismo , Glicosilação , Imidazóis/química , Imidazóis/metabolismo , Cinética , Oxirredução , Picratos/antagonistas & inibidores , Células Vegetais/química , Células Vegetais/metabolismo , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo
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