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1.
J Med Chem ; 63(8): 4090-4106, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202425

RESUMO

Fatty-acid binding protein 4 (FABP4) is a promising therapeutic target for immunometabolic diseases, while its potential for systemic inflammatory response syndrome treatment has not been explored. Here, a series of 2-(phenylamino)benzoic acids as novel and potent FABP4 inhibitors are rationally designed based on an interesting fragment that adopts multiple binding poses within FABP4. A fusion of these binding poses leads to the design of compound 3 with an ∼460-fold improvement in binding affinity compared to the initial fragment. A subsequent structure-aided optimization upon 3 results in a promising lead (17) with the highest binding affinity among all the inhibitors, exerting a significant anti-inflammatory effect in cells and effectively attenuating a systemic inflammatory damage in mice. Our work therefore presents a good example of lead compound discovery derived from the multiple binding poses of a fragment and provides a candidate for development of drugs against inflammation-related diseases.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/metabolismo , Descoberta de Drogas/métodos , Proteínas de Ligação a Ácido Graxo/antagonistas & inibidores , Proteínas de Ligação a Ácido Graxo/metabolismo , Células 3T3 , Administração Oral , Animais , Anti-Inflamatórios/química , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/química , Compostos de Bifenilo/metabolismo , Células CACO-2 , Relação Dose-Resposta a Droga , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Pirazóis/administração & dosagem , Pirazóis/química , Pirazóis/metabolismo , Resultado do Tratamento
2.
Food Funct ; 11(1): 871-882, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31942589

RESUMO

This research focused on the effects of electron beam irradiation (EBI) on the hydrolysis and antioxidant activity of rice proteins (RPs). The RPs were treated with 0, 5, 10, 20 and 30 kGy doses of EBI. The results showed that EBI pretreatment improved significantly (P < 0.05) the degree of hydrolysis, increasing the DH value by more than 15.09% at a dose of 30 kGy. In addition, radical scavenging results showed that EBI treatment had effects on antioxidant activity and could increase the DPPH and ABTS+ radical scavenging activity of rice protein hydrolysates (RPHs) by 32.06% and 79.11%, respectively (30 kGy). The CAA test also confirmed that EBI pretreatment could effectively improve the ability of RPHs to remove intracellular free radicals. Scanning electron microscopy indicated that EBI treatment destroyed microstructures and resulted in cracks and fragments of RPs. Circular dichroism analysis showed that EBI affected the secondary structure of RPs by destroying the α-helix structure. Changes in the UV visible spectra indicated unfolding of RPs by EBI. Amino acid and molecular weight distribution analysis revealed that EBI pretreatment could increase the ratio of antioxidant-related amino acids and produce smaller peptides. Therefore, EBI pretreatment is an efficient method to promote protein proteolysis due to its effect on the molecular conformation as well as on protein microstructure. Moreover, EBI treatment applied before enzymatic hydrolysis has the potential to prepare hydrolysates with high bioactivity.


Assuntos
Antioxidantes/farmacologia , Oryza , Proteínas de Plantas/química , Antioxidantes/química , Compostos de Bifenilo/metabolismo , Relação Dose-Resposta à Radiação , Elétrons , Células Hep G2/efeitos dos fármacos , Humanos , Picratos/metabolismo , Proteínas de Plantas/efeitos da radiação , Proteólise
3.
Appl Biochem Biotechnol ; 190(2): 391-409, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31363982

RESUMO

Microorganisms that survive in the high salt environment have been shown to be a potential source for metabolites with pharmaceutical importance. In the present study, we have investigated the effect of 5 and 10% (w/v) NaCl on growth, biochemical changes, and metabolite production in seven moderately halophilic bacteria isolated from the salterns/mangrove area of South India. Metabolite production by Bacillus VITPS3 increased by 3.18-fold in the presence of 10% (w/v) NaCl concentration. Total phenolic and flavonoid content increased in Bacillus VITPS5 (11.3-fold) and Planococcus maritimus VITP21 (5.99-fold) whereas ß-carotene content was less at higher NaCl concentrations. VITP21 and VITPS5, in response to NaCl, produced metabolites with higher (6.72- and 4.91-fold) DPPH and ABTS radical scavenging activity. UV/visible spectrophotometry of the extracts confirmed the presence of flavonoids, phenolics, and related compounds. 1H-NMR spectra indicated substantial changes in the metabolite production in response to salt concentration. Principal component analysis (PCA) revealed that VITP21 extracts exhibited the highest antioxidant activity compared with other extracts. The present study presents the first report on the comparative analysis of pigment production by moderate halophilic bacteria, in response to the effect of salt and their relation to radical scavenging property.


Assuntos
Antioxidantes/farmacologia , Bacillus/efeitos dos fármacos , Pigmentos Biológicos/biossíntese , Planococcus (Bactéria)/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Bacillus/crescimento & desenvolvimento , Bacillus/metabolismo , Compostos de Bifenilo/metabolismo , Depuradores de Radicais Livres/farmacologia , Picratos/metabolismo , Planococcus (Bactéria)/crescimento & desenvolvimento , Planococcus (Bactéria)/metabolismo
4.
Chem Biodivers ; 17(1): e1900394, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31618522

RESUMO

We aimed in the present study to investigate the chemical composition, the antioxidant capacities as well as the in vitro fermentation properties of Salvia officinalis leaves aqueous extract (SOLAE) grown in four regions of northwestern Tunisia. Our data firstly indicated a spatial variation (P<0.05) in condensed tannins, total lipids, polyphenols and flavonoids contents. The HPLC-PDA-ESI-MS/MS-LC/HR-ESI-MS technique allowed to the identification of 13 phenolic compounds and showed that protocatechuic acid is the major constituent of the plant leaves grown in Tabarka, Ain Draham and Testour. The SOLAE of the plant grown in Tabarka presents the most potent scavenging activity against DPPH radical and had the highest percentage of inhibition. More importantly, we found in the present study that the digestibility of dry matter and in vitro fermentation showed a significant variation between the regions and the animal species. Also, we showed a very positive correlation between antioxidant properties and phenolic compounds contents. In conclusion, we suggest that SOLAE had potential beneficial effects owing in part to its antioxidant and ROS scavenging activities. Therefore, S. officinalis can be proposed as an additive food for animals' nutrition and health.


Assuntos
Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Fermentação , Compostos Fitoquímicos/farmacologia , Picratos/antagonistas & inibidores , Salvia officinalis/metabolismo , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Compostos de Bifenilo/metabolismo , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos , Cabras , Hidroxibenzoatos/análise , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/farmacologia , Espectrometria de Massas , Fenol/análise , Fenol/metabolismo , Fenol/farmacologia , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/metabolismo , Picratos/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Salvia officinalis/química , Salvia officinalis/crescimento & desenvolvimento , Ovinos , Tunísia
5.
J Appl Microbiol ; 128(3): 853-861, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31733170

RESUMO

AIM: The aim of the present study was to investigate the in vitro antioxidant activity of yeast strains isolated from virgin olive oil. METHODS AND RESULTS: The 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free-radical scavenging activity of single cultures of 24 yeast strains belonging to eight species isolated from virgin olive oil was evaluated and compared with that of the reference yeast Saccharomyces boulardii. All the yeasts studied in vitro showed antioxidant activity similar to or superior to that of the reference yeast. The highest antioxidant activity was observed in Nakazawaea wickerhamii, which exceeded the value reached by the reference strain S. boulardii, while the significantly lowest values were observed in the Candida adriatica, Candida diddensiae and Barnettozyma californica strains. Tests performed with virgin olive oil enriched with Wickerhamomyces anomalus and S. boulardii yeast biomasses showed a positive correlation between the microbial biomass used and the percentage of antioxidant activity observed during 60 days of storage. Survival in virgin olive oil was also significantly higher for W. anomalus compared to S. boulardii. CONCLUSIONS: All the oil-borne yeasts studied showed DPPH free-radical scavenging activity in both aqueous and oily media. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time, the antioxidant activity of the microbiota of virgin olive oil is reported. This activity may indicate the probiotic characteristics of the microbiota.


Assuntos
Antioxidantes/metabolismo , Azeite de Oliva , Saccharomycetales/isolamento & purificação , Saccharomycetales/metabolismo , Biomassa , Compostos de Bifenilo/metabolismo , Microbiologia de Alimentos , Microbiota , Picratos/metabolismo , Probióticos , Saccharomycetales/classificação , Saccharomycetales/crescimento & desenvolvimento
6.
Biomed Chromatogr ; 34(2): e4734, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31692001

RESUMO

Laportea bulbifera, named Hong He Ma in Chinese, is a Chinese herbal medicine commonly used by the Miao nationality of China. In this study, 43 batches of L. bulbifera were collected from different origins in China. Ethanol, ethyl acetate and petroleum ether were used to prepare different extracts of the plant. UHPLC technique was used to establish the fingerprints, whereas DPPH assay and RAW264.7 inflammatory cell models were used to evaluate the antioxidant and anti-inflammatory activities, respectively. Moreover, the spectrum-effect relationship between relative peak area of common peaks and efficacy value was set up by multivariate statistical analysis. Furthermore, 10 batches were selected randomly for validation of those models. The results showed that ethyl acetate and petroleum ether extracts possess excellent antioxidant and anti-inflammatory activities, respectively. Peaks A6 and A7 demonstrated the greatest antioxidant activity, while peak A17 showed the strongest anti-inflammatory activity. After a verified experiment, the result was obtained and illustrated that the spectrum-effect relationship which we established could reliably infer antioxidant and anti-inflammatory compounds of the Chinese herbal medicine.


Assuntos
Anti-Inflamatórios , Antioxidantes , Extratos Vegetais , Urticaceae/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Camundongos , Análise Multivariada , Picratos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/antagonistas & inibidores
7.
Med Sci Monit ; 25: 8579-8586, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724562

RESUMO

BACKGROUND Dysregulation of the Hedgehog (Hh) pathway modulates various aspects of hematologic and solid tumors, but its effects in human Natural killer/T-cell lymphoma (NKTCL) are unclear. Moreover, no study has examined the consequences of pharmacologically inhibiting Hh signaling in NKTCL cell lines. MATERIAL AND METHODS In this study, the expression of Smoothened (Smo) and Glioma-associated oncogene 1 (Gli1) in NKTCL tissue were scrutinized. Two human NKTCL cell lines, SNK6 and SNT8, were subjected to various doses of sonidegib (a Smo inhibitor) and incubated for distinct durations. The cell apoptosis was examined by flow cytometry, CCK-8 assay was run to assess proliferation, and protein levels were quantified by Western blotting. RESULTS Both Smo and Gli1 expression were higher in NKTCL tissue than in Lymphoid Reactive Hyperplasia (LRH). Sonidegib significantly suppressed proliferation in NKTCL cells and the effect was dose-dependent. Further analysis revealed that sonidegib treatment elevated the number of apoptotic cells in a dose- and time-dependent manner. In addition, sonidegib downregulated Smo and Gli1expression in NKTCL cells. CONCLUSIONS The Hh pathway is crucial to the development of NKTCL and thus holds huge promise as a treatment for this disease.


Assuntos
Compostos de Bifenilo/farmacologia , Linfoma de Células T/metabolismo , Piridinas/farmacologia , Receptor Smoothened/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Linfoma , Piridinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor Smoothened/metabolismo , Proteína GLI1 em Dedos de Zinco
8.
Mar Drugs ; 17(11)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739542

RESUMO

Antioxidant peptides have elicited interest for the versatility of their use in the food and pharmaceutical industry. In the current study, antioxidant peptides were prepared by microwave-assisted alkaline protease hydrolysis of collagen from sea cucumber (Acaudina molpadioides). The results showed that microwave irradiation significantly improved the degree of hydrolysis of collagen and the hydroxyl radical (OH⋅) scavenging activity of hydrolysate. The content and OH⋅ scavenging activity of collagen peptides with molecular weight ≤ 1 kDa (CPS) in the hydrolysate obtained at 250 W increased significantly compared with the non-microwave-assisted control. CPS could scavenge OH⋅ and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical in a dose-dependent manner. The scavenging activity of OH⋅ and DPPH radical was 93.1% and 41.2%, respectively, at CPS concentration of 1 mg/mL. CPS could significantly promote RAW264.7 cell proliferation and reduce the Reactive Oxygen Species (ROS) level of H2O2-induced damage in RAW264.7 cells in a dose-dependent manner. Furthermore, all CPS-treated groups exhibited an increase in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and a decrease in malondialdehyde (MDA) level compared with the control. These results showed that CPS could effectively protect RAW264.7 cells from H2O2-induced damage, implying the potential utilization of CPS as a natural antioxidant for food and pharmaceutical applications.


Assuntos
Antioxidantes/farmacologia , Colágeno/metabolismo , Peróxido de Hidrogênio/farmacologia , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Compostos de Bifenilo/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Hidrólise , Radical Hidroxila/metabolismo , Malondialdeído/metabolismo , Camundongos , Micro-Ondas , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
9.
Int J Biol Macromol ; 140: 631-636, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415860

RESUMO

This study was conducted to confirm the effects of salinity stress on bioactive compounds and antioxidant activity of wheat microgreen extract. The microgreens were cultivated for 8 days in organic media with different concentrations of Na [0 (control), 12.5, 25, 50, and 100 mM from sodium chloride] which was contained in a growth chamber with controlled temperature (20/15 °C, day/night), light (14/10 h, light/dark; intensity 150 µmol·m-2·s-1 with quantum dot light-emitting diodes), and humidity (60%). Treatment with increasing concentrations of Na resulted in an increase in the Na content of microgreens. Treatment with 12.5 mM of NaCl significantly maximized ß-carotene (1.21 µg/mL), phenolic acid (41.70 µg/mL), flavonoid (165.47 µg/mL), and vitamin C (29.51 µg/mL) levels and the nitrite-scavenging activities (37.33%) in wheat microgreen extracts. In addition, the salt-stress caused due to treatment with 25 mM of NaCl resulted in the highest anthocyanin (51.43 µg/mL), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (89.31%), and 2,2-diphenyl-1-picrylhydrazyl (63.28%) radical-scavenging activity. Therefore, attaining adequate levels of salt-stress may be useful for the industrial manufacturing of new products from wheat microgreen extract.


Assuntos
Antioxidantes/metabolismo , Produtos Biológicos/metabolismo , Extratos Vegetais/metabolismo , Estresse Salino/fisiologia , Sódio/metabolismo , Triticum/metabolismo , Triticum/fisiologia , Antocianinas/metabolismo , Compostos de Bifenilo/metabolismo , Flavonoides/metabolismo , Hidroxibenzoatos/metabolismo , Fenóis/metabolismo , Vitaminas/metabolismo , beta Caroteno/metabolismo
10.
Eur J Med Chem ; 182: 111596, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31419776

RESUMO

Facing the complexity of Alzheimer's disease (AD), it is now currently admitted that a therapeutic pleiotropic intervention is needed to alter its progression. Among the major hallmarks of the disease, the amyloid pathology and the oxidative stress are closely related. We propose in this study to develop original Multi-Target Directed Ligands (MTDL) able to impact at the same time Aß protein accumulation and toxicity of Reactive Oxygen Species (ROS) in neuronal cells. Such MTDL were obtained by linking on a central piperidine two scaffolds of interest: a typical aminochlorobenzophenone present in numerous 5-HT4R agonists, and diverse antioxidant chemotypes. Interestingly, the most active compound 9g possesses a Ki of 12.7 nM towards 5-HT4R and an antioxidant activity in vitro and in cellulo.


Assuntos
Antioxidantes/farmacologia , Receptores 5-HT4 de Serotonina/metabolismo , Agonistas do Receptor 5-HT4 de Serotonina/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Antioxidantes/síntese química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/metabolismo , Células COS , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Estrutura Molecular , Picratos/antagonistas & inibidores , Picratos/metabolismo , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Agonistas do Receptor 5-HT4 de Serotonina/síntese química , Agonistas do Receptor 5-HT4 de Serotonina/química , Relação Estrutura-Atividade
11.
Eur J Med Chem ; 179: 515-526, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276896

RESUMO

Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the naphthoquinone- (5), thiazol- (12), and the azo-based (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, naphthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.


Assuntos
Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos Organosselênicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Células MCF-7 , Estrutura Molecular , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/química , Picratos/antagonistas & inibidores , Picratos/metabolismo , Relação Estrutura-Atividade
12.
AAPS PharmSciTech ; 20(6): 244, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286296

RESUMO

Cyclodextrin (CD) inclusions are generally used to increase the solubility of poorly soluble drugs. In this study, magnolol (MAG) was used as a model drug for exploring the effects of CD on the degradation of pharmaceutical drugs by intestinal microflora. MAG/ß-cyclodextrin (ß-CD) and MAG/hydroxypropyl-ß-CD (HP-ß-CD) inclusion complexes were successfully prepared by the saturated aqueous solution and freeze-drying methods, respectively. Structural characterisation along with analyses of solubility, residual water content and drug content of the inclusion complexes was performed. The intestinal microflora of male rats was used to study MAG degradation in vitro. At three concentrations, the degradation of both the inclusion complexes was slower than that of the MAG monomer, MAG and CD mixtures and the MAG-poloxamer 188 micelle. There were no statistically significant differences in the degradation of the MAG/ß-CD and MAG/HP-ß-CD inclusion complexes. A simulation first-order equation of the degradation parameters revealed that the degradation of the inclusion complexes was slower and pronounced, judging by slope. The experimental findings were verified by molecular docking for predicting the stable molecular structure of the inclusion complexes. In conclusion, the inclusion complexes partially protected MAG from degradation by the intestinal bacteria.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Bactérias/metabolismo , Compostos de Bifenilo/metabolismo , Intestinos/microbiologia , Lignanas/metabolismo , beta-Ciclodextrinas/química , Animais , Liofilização , Masculino , Simulação de Acoplamento Molecular , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Solubilidade
13.
Biomed Chromatogr ; 33(11): e4635, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31257616

RESUMO

Gynura procumbens (Lour.) Merr. is traditionally used as a raw material for making dumplings or steamed stuffed buns, and its fresh leaves are boiled with water for tea. Herein, we established an ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) combined with characteristic ion filtration (CIF) strategy to rapidly screen active ingredients with antioxidant and anti-inflammatory properties in G. procumbens. This strategy involved screening the active part of G. procumbens using antioxidation and anti-inflammatory activity assays; discovering the active compounds by speculating on the active site's chemical composition by UHPLC-Q-TOF-MS/MS plus CIF; and verifying the active compounds' activities. The ethyl acetate extract (EEAF) of G. procumbens was the major active site. Eighty-one compounds were identified from the EEAF using UHPLC-Q-TOF-MS/MS plus CIF. Furthermore, polyphenols such as cynarine, isochlorogenic acids A and isochlorogenic acids C have excellent antioxidizing and anti-inflammatory activities. This study provides a practical strategy for rapid in vitro screening of the antioxidizing and anti-inflammatory activities of traditional vegetables and herbs and identification of active ingredients.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Asteraceae/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/farmacologia , Espectrometria de Massas em Tandem/métodos , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/análise , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Picratos/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Células RAW 264.7
14.
Biomed Res Int ; 2019: 1847130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240205

RESUMO

Over years, various biological constituents are isolated from Traditional Chinese Medicine and confirmed to show multifunctional activities. Magnolol, a hydroxylated biphenyl natural compound isolated from Magnolia officinalis, has been extensively documented and shows a range of biological activities. Many signaling pathways include, but are not limited to, NF-κB/MAPK, Nrf2/HO-1, and PI3K/Akt pathways, which are implicated in the biological functions mediated by magnolol. Thus, magnolol is considered as a promising therapeutic agent for clinic research. However, the low water solubility, the low bioavailability, and the rapid metabolism of magnolol dramatically limit its clinical application. In this review, we will comprehensively discuss the last five-year progress of the biological activities of magnolol, including anti-inflammatory, antimicroorganism, antioxidative, anticancer, neuroprotective, cardiovascular protection, metabolism regulation, and ion-mediating activity.


Assuntos
Compostos de Bifenilo/metabolismo , Compostos de Bifenilo/farmacologia , Lignanas/metabolismo , Lignanas/farmacologia , Medicina Tradicional Chinesa , Anti-Inflamatórios/análise , Antineoplásicos/análise , Antioxidantes/análise , Compostos de Bifenilo/química , Compostos de Bifenilo/uso terapêutico , Fármacos Cardiovasculares/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Lignanas/química , Lignanas/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Magnolia/química , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/análise , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Appl Microbiol Biotechnol ; 103(16): 6825-6836, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31240368

RESUMO

Polychlorinated biphenyls (PCBs) are a group of persistent organic pollutants (POPs) widely existing in the environment. Arthrobacter sp. YC-RL1 is a biphenyl-degrading bacterium that shows metabolic versatility towards aromatic compounds. A 2-hydroxy-6-oxo-6-phenylhexa-2, 4-dienoate (HOPDA) hydrolase (BphD) gene involved in the biodegradation of biphenyl was cloned from strain YC-RL1 and heterologously expressed in Escherichia coli BL21 (DE3). The recombinant BphDYC-RL1 was purified and characterized. BphDYC-RL1 showed the highest activity at 45 °C and pH 7. It was stable under a wide range of temperature (20-50 °C). The enzyme had a Km value of 0.14 mM, Kcat of 11.61 s-1, and Vmax of 0.027 U/mg. Temperature dependence catalysis exhibited a biphasic Arrhenius Plot with a transition at 20 °C. BphDYC-RL1 was inactivated by SDS, Tween 20, Tween 80, Trition X-100, DTT, CHAPS, NBS, PMSF, and DEPC, but insensitive to EDTA. Site-directed mutagenesis of the active-site residues revealed that the catalytic triad residues (Ser115, His275, and Asp247) of BphDYC-RL1 were necessary for its activity. The investigation of BphDYC-RL1 not only provides new potential enzyme resource for the biodegradation of biphenyl but also helps deepen our understanding on the catalytic process and mechanism.


Assuntos
Arthrobacter/enzimologia , Compostos de Bifenilo/metabolismo , Fungicidas Industriais/metabolismo , Hidrolases/metabolismo , Arthrobacter/genética , Biotransformação , Domínio Catalítico , Clonagem Molecular , Análise Mutacional de DNA , Inibidores Enzimáticos/análise , Estabilidade Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Concentração de Íons de Hidrogênio , Hidrolases/genética , Cinética , Mutagênese Sítio-Dirigida , Temperatura
16.
Biomed Chromatogr ; 33(10): e4624, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31215046

RESUMO

Cimicifugae Rhizoma (sheng ma) is a well-known traditional Chinese medicine, which has been demonstrated to possess anti-inflammatory, antipyretic and analgesic activities. In the present study, a simple and efficient HPLC-DAD (high-performance liquid chromatography coupled with diode array detection) method was developed and validated for simultaneous quantification of 19 chemical components (including 16 phenolic acids, one coumarin and two alkaloids) in Cimicifugae Rhizoma. The result indicated that this method could effectively evaluate the quality of Cimicifugae Rhizoma and provide a valuable reference for further study. Additionally, the antioxidant activity of Cimicifugae Rhizoma was evaluated by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay. The results showed that the content of phenolic acids and antioxidant activity exhibited significant correlation coefficients.


Assuntos
Antioxidantes , Cromatografia Líquida de Alta Pressão/métodos , Cimicifuga/química , Medicamentos de Ervas Chinesas , Alcaloides/análise , Alcaloides/isolamento & purificação , Alcaloides/metabolismo , Antioxidantes/análise , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Compostos de Bifenilo/metabolismo , Cumarínicos/análise , Cumarínicos/isolamento & purificação , Cumarínicos/metabolismo , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Radicais Livres/análise , Radicais Livres/isolamento & purificação , Radicais Livres/metabolismo , Hidroxibenzoatos/análise , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/metabolismo , Limite de Detecção , Modelos Lineares , Picratos/metabolismo , Reprodutibilidade dos Testes
17.
Chem Biol Interact ; 308: 339-349, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170387

RESUMO

Magnolol, the most abundant bioactive constituent of the Chinese herb Magnolia officinalis, has been found with multiple biological activities, including anti-oxidative, anti-inflammatory and enzyme-regulatory activities. In this study, the inhibitory effects and inhibition mechanism of magnolol on human carboxylesterases (hCEs), the key enzymes responsible for the hydrolytic metabolism of a variety of endogenous esters as well as ester-bearing drugs, have been well-investigated. The results demonstrate that magnolol strongly inhibits hCE1-mediated hydrolysis of various substrates, whereas the inhibition of hCE2 by magnolol is substrate-dependent, ranging from strong to moderate. Inhibition of intracellular hCE1 and hCE2 by magnolol was also investigated in living HepG2 cells, and the results showed that magnolol could strongly inhibit intracellular hCE1, while the inhibition of intracellular hCE2 was weak. Inhibition kinetic analyses and docking simulations revealed that magnolol inhibited both hCE1 and hCE2 in a mixed manner, which could be partially attributed to its binding at two distinct ligand-binding sites in each carboxylesterase, including the catalytic cavity and the regulatory domain. In addition, the potential risk of the metabolic interactions of magnolol via hCE1 inhibition was predicted on the basis of a series of available pharmacokinetic data and the inhibition constants. All these findings are very helpful in deciphering the metabolic interactions between magnolol and hCEs, and also very useful for avoiding deleterious interactions via inhibition of hCEs.


Assuntos
Compostos de Bifenilo/metabolismo , Hidrolases de Éster Carboxílico/metabolismo , Lignanas/metabolismo , Sítios de Ligação , Biocatálise , Compostos de Bifenilo/química , Hidrolases de Éster Carboxílico/antagonistas & inibidores , Domínio Catalítico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Células Hep G2 , Humanos , Hidrólise , Cinética , Lignanas/química , Simulação de Acoplamento Molecular
18.
Int J Biol Sci ; 15(5): 1052-1071, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182925

RESUMO

In pursuit of a novel approach in colon cancer therapy, we explored the ability of ruthenium baicalein complex to eradicate colon cancer by efficiently targeting various apoptotic pathways on human colon cancer cell line and on a DMH and DSS induced murine model of colorectal cancer. In this study, we provide direct proof of the chemotherapeutic potential of the ruthenium baicalein complex by activating p-53 dependent intrinsic apoptosis and modulating the AKT/mTOR and WNT/ß- catenin pathways. The ruthenium baicalein complex was synthesized and its characterizations were accomplished through various spectroscopic techniques followed by assessment of antioxidant potential by DPPH, FRAP, and ABTS methods. In vitro study established that the complex increased p53 and caspase-3 expressions while down regulating VEGF and mTOR expression, induced apoptosis, and DNA fragmentation in the HT-29 cells. Acute and sub-acute toxicity study was also considered and results from in vivo study revealed that complex was effective in suppressing ACF multiplicity and hyperplastic lesions and also raised the CAT, SOD, and glutathione levels. Furthermore, the complex decreased cell proliferation and increased apoptotic events in tumor cells correlated with the upregulation of Bax and downregulation of Bcl2, WNT and ß- catenin expressions. Our findings from the in vitro and in vivo study provide robust confirmation that ruthenium baicalein complex possesses a potential chemotherapeutic activity against colon cancer and is competent in reducing ACF multiplicity, hyperplastic lesions in the colon tissues of rats by inducing apoptosis.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Flavanonas/química , Rutênio/química , Animais , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/metabolismo , Catalase/metabolismo , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Glutationa/metabolismo , Células HT29 , Humanos , Masculino , Picratos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/metabolismo , beta Catenina/metabolismo
19.
Molecules ; 24(10)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137531

RESUMO

Alnus sibirica (AS) is geographically distributed in Korea, Japan, Northeast China, and Russia. Various anti-oxidant, anti-inflammation, anti-atopic dermatitis and anti-cancer biological effects of AS have been reported. Enzymatic hydrolysis decomposes the sugar bond attached to glycoside into aglycone which, generally, has a superior biological activity, compared to glycoside. Enzymatic hydrolysis of the extract (EAS) from AS was processed and the isolated compounds were investigated-hirsutanonol (1), hirsutenone (2), rubranol (3), and muricarpon B (4). The structures of these compounds were elucidated, and the biological activities were assessed. The ability of EAS and the compounds (1-4) to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and Nitroblue tetrazolium (NBT) superoxide, and to inhibit NO production was evaluated in vitro. EAS showed more potent antioxidant and anti-inflammatory activity than AS. All investigated compounds showed excellent antioxidant and anti-inflammatory activities.


Assuntos
Alnus/química , Compostos de Bifenilo/metabolismo , Diarileptanoides/isolamento & purificação , Etanol/química , Óxido Nítrico/biossíntese , Nitroazul de Tetrazólio/metabolismo , Picratos/metabolismo , Extratos Vegetais/química , Superóxidos/metabolismo , Animais , Hidrólise , Concentração Inibidora 50 , Camundongos , Células RAW 264.7
20.
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
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