Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.005
Filtrar
1.
Anticancer Res ; 41(9): 4377-4385, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475057

RESUMO

BACKGROUND/AIM: Expression of pleckstrin homology-like domain family A member 2 (PHLDA2) has been reported to be suppressed or activated in several cases of malignant tumors. However, its apoptotic regulatory mechanism and role in gastric cancer are not understood. This study examined the role of PHLDA2 in apoptosis in gastric cancer. MATERIALS AND METHODS: We used cell culture, western blotting, semiquantitative reverse transcription polymerase chain reaction, MTT assays, and PHLDA2 knockdown with short hairpin RNA (shRNA). RESULTS: To identify the pathway associated with HGF-induced PHLDA2 up-regulation, the cells were treated with PI3-kinase inhibitor (LY294002), MEK inhibitor (PD098059), or p38 inhibitor (SB203580) and then analyzed by western blotting. HGF-mediated changes in PHLDA2 protein levels were only decreased by LY294002. PHLDA2-shRNA cells showed decreased levels of p53 and increased levels of pAKT. Furthermore, HGF-induced cell proliferation and in vitro invasion were increased in PHLDA2 knockdown cells and HGF-induced cell apoptosis was increased in PHLDA2 knockdown cells. CONCLUSION: PHLDA2 plays a role in gastric cancer tumorigenesis by inhibiting apoptosis through the PI3K/AKT pathway.


Assuntos
Fator de Crescimento de Hepatócito/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/metabolismo , Regulação para Cima , Apoptose , Linhagem Celular Tumoral , Cromonas/farmacologia , Flavonoides/farmacologia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Imidazóis , Morfolinas/farmacologia , Proteínas Nucleares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Piridinas
2.
Int J Biol Macromol ; 187: 976-987, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34333006

RESUMO

Coronavirus 3C-like protease (3CLpro) is a crucial target for treating coronavirus diseases including COVID-19. Our preliminary screening showed that Ampelopsis grossedentata extract (AGE) displayed potent SARS-CoV-2-3CLpro inhibitory activity, but the key constituents with SARS-CoV-2-3CLpro inhibitory effect and their mechanisms were unrevealed. Herein, a practical strategy via integrating bioactivity-guided fractionation and purification, mass spectrometry-based peptide profiling and time-dependent biochemical assay, was applied to identify the crucial constituents in AGE and to uncover their inhibitory mechanisms. The results demonstrated that the flavonoid-rich fractions (10-17.5 min) displayed strong SARS-CoV-2-3CLpro inhibitory activities, while the constituents in these fractions were isolated and their SARS-CoV-2-3CLpro inhibitory activities were investigated. Among all isolated flavonoids, dihydromyricetin, isodihydromyricetin and myricetin strongly inhibited SARS-CoV-2 3CLpro in a time-dependent manner. Further investigations demonstrated that myricetin could covalently bind on SARS-CoV-2 3CLpro at Cys300 and Cys44, while dihydromyricetin and isodihydromyricetin covalently bound at Cys300. Covalent docking coupling with molecular dynamics simulations showed the detailed interactions between the orthoquinone form of myricetin and two covalent binding sites (surrounding Cys300 and Cys44) of SARS-CoV-2 3CLpro. Collectively, the flavonoids in AGE strongly and time-dependently inhibit SARS-CoV-2 3CLpro, while the newly identified SARS-CoV-2 3CLpro inhibitors in AGE offer promising lead compounds for developing novel antiviral agents.


Assuntos
Proteases Virais 3C/química , Proteases Virais 3C/metabolismo , Ampelopsis/química , Antivirais/farmacologia , Flavonoides/farmacologia , SARS-CoV-2/enzimologia , Antivirais/química , Sítios de Ligação/efeitos dos fármacos , Cisteína/metabolismo , Flavonoides/química , Flavonóis/química , Flavonóis/farmacologia , Espectrometria de Massas , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Ligação Proteica/efeitos dos fármacos , Conformação Proteica/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos
3.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445360

RESUMO

Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.


Assuntos
Flavonoides/uso terapêutico , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/prevenção & controle , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Citoproteção/efeitos dos fármacos , Flavonoides/farmacologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Medicina de Precisão/métodos , Prognóstico
4.
Viruses ; 13(7)2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34372556

RESUMO

Influenza viruses cause respiratory infections in humans and animals, which have high morbidity and mortality rates. Although several drugs that inhibit viral neuraminidase are used to treat influenza infections, the emergence of resistant viruses necessitates the urgent development of new antiviral drugs. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that exhibits antiviral activity against enterovirus 71 (EV71) by inhibiting viral 3C protease activity. In this study, we evaluated the antiviral activity of chrysin against influenza A/Puerto Rico/8/34 (A/PR/8). Chrysin significantly inhibited A/PR/8-mediated cell death and the replication of A/PR/8 at concentrations up to 2 µM. Viral hemagglutinin expression was also markedly decreased by the chrysin treatment in A/PR/8-infected cells. Through the time course experiment and time-of-addition assay, we found that chrysin inhibited viral infection at the early stages of the replication cycle. Additionally, the nucleoprotein expression of A/PR/8 in A549 cells was reduced upon treatment with chrysin. Regarding the mechanism of action, we found that chrysin inhibited autophagy activation by increasing the phosphorylation of mammalian target of rapamycin (mTOR). We also confirmed a decrease in LC3B expression and LC3-positive puncta levels in A/PR/8-infected cells. These results suggest that chrysin exhibits antiviral activity by activating mTOR and inhibiting autophagy to inhibit the replication of A/PR/8 in the early stages of infection.


Assuntos
Flavonoides/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Células A549 , Animais , Antivirais/farmacologia , Autofagia/efeitos dos fármacos , Cães , Flavonoides/metabolismo , Humanos , Vírus da Influenza A/patogenicidade , Influenza Humana/tratamento farmacológico , Influenza Humana/metabolismo , Células Madin Darby de Rim Canino , Neuraminidase/metabolismo , Proteínas Virais/metabolismo
5.
Molecules ; 26(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34443305

RESUMO

The local botanical Imperata cylindrica in Cameroon was investigated for its antibacterial potency. The methanol extract afforded a total of seven compounds, including five hitherto unreported compounds comprising three flavonoids (1-3) and two C-15 isoprenoid analogues (4 and 5) together with known derivatives (6 and 7). The novelty of the flavonoids was related to the presence of both methyl and prenyl groups. The potential origin of the methyl in the flavonoids is discussed, as well as the chemophenetic significance of our findings. Isolation was performed over repeated silica gel and Sephadex LH-20 column chromatography and the structures were elucidated by (NMR and MS). The crude methanol extract and isolated compounds showed considerable antibacterial potency against a panel of multi-drug resistant (MDR) bacterial strains. The best MIC values were obtained with compound (2) against S. aureus ATCC 25923 (32 µg/mL) and MRSA1 (16 µg/mL).


Assuntos
Antibacterianos/farmacologia , Flavonoides/farmacologia , Poaceae/química , Prenilação , Terpenos/farmacologia , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Flavonoides/química , Flavonoides/isolamento & purificação , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Terpenos/química , Terpenos/isolamento & purificação
6.
Molecules ; 26(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34443495

RESUMO

Phytochemical investigation and chromatographic separation of extracts from the actinobacteria strain Saccharomonospora piscinae that was isolated from dried fishpond sediment of Kouhu township, in the south of Taiwan, led to the isolation of three new compounds, saccharpiscinols A-C (1-3, respectively), and three new natural products, namely (2S)-5,7,3',4'-tetrahydroxy-6,8-dimethylflavanone (4), methyl-4-hydroxy-2-methoxy-6-methylbenzoate (5), and (±)-7-acetyl-4,8-dihydroxy-6-methyl-1-tetralone (6). Compounds 4-6 were reported before as synthesized products, herein, they are reported from nature for the first time. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Saccharpiscinol A showed inhibitory activities against LPS-induced NO production.


Assuntos
Actinobacteria/química , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Animais , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Misturas Complexas , Flavonoides/química , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Células RAW 264.7
7.
Molecules ; 26(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34443365

RESUMO

(±)-Anastatins A and B are flavonoids isolated from Anastatica hierochuntica. In a previous study, twenty-four di- and tri-substituted novel derivatives of anastatins were designed and their preliminary antioxidant activities were evaluated. In the present study, the protective effect of myocardial ischemia-reperfusion (I/R) and the systematic antioxidant capacity of 24 derivatives were further studied. Compound 13 was the most potent among all the compounds studied, which increased the survival of H9c2 cells to 80.82%. The antioxidant capability of compound 13 was evaluated in ferric reducing antioxidant power, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, and 2,2-diphenyl-1-picrylhydrazyl assays. It was observed that compound 13 significantly reduced infarcted areas and improved histopathological and electrocardiogram changes in rats with myocardial I/R injury. Moreover, compound 13 decreased the leakage rates of serum lactate dehydrogenase, creatine kinase, and malonyldialdehyde from rat myocardial tissues and increased the level of glutathione and superoxide dismutase activities following myocardial I/R injury in rats. Taken together, we concluded that compound 13 had potent cardioprotective effects against myocardial I/R injury both in vitro and in vivo owing to its extensive antioxidant activities.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/uso terapêutico , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos
8.
Braz J Med Biol Res ; 54(10): e11203, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34406208

RESUMO

Phytochemical studies of the species Pavonia glazioviana were performed. Quercetin, kaempferol, acacetin, and trimethoxylated flavonoid compounds (which present biological activity) were isolated. We aimed to evaluate the in silico, in vitro, and ex vivo toxicity of flavonoid 5,7-dihydroxy-3,8,4'-trimethoxy (Pg-1) obtained from P. glazioviana through chemical structure analyses, toxicity assessment, and predictive bioactive properties, using human samples in in vitro tests. In silico analysis suggested that Pg-1 presents a good absorption index for penetrating biological membranes (for oral bioavailability), while also suggesting potential antimutagenic, anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic, and apoptosis agonist bioactivities. Assessment of hemolytic and genotoxic effects revealed low hemolysis rates in red blood cells with no cellular toxicity in oral mucosa cells. The reduced cytotoxic activity suggested the safety of the concentrations used (500-1000 µg/mL), and demonstrated the varied interactions of Pg-1 with the analyzed cells. The data obtained in the present study suggested potential therapeutic application, and the non-toxic profile indicated viability for future studies.


Assuntos
Flavonoides , Extratos Vegetais , Antioxidantes/farmacologia , Apoptose , Simulação por Computador , Flavonoides/farmacologia , Humanos
9.
Microb Pathog ; 159: 105121, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34343655

RESUMO

The emergence of multidrug resistance (MDR) and extensive drug resistance (XDR) in Klebsiella pneumoniae strains has posed great threats to conventional antibiotics. Previous studies have shown that plant-derived flavonoids have inhibitory functions against pathogens. However, in K. pneumoniae, the antibacterial activity of different flavonoids against growth and biofilm formation remains a mystery. The aim of the present study was to evaluate the antioxidant abilities of different flavonoids, to screen active ingredients and to identify their inhibitory effects on K. pneumoniae growth and biofilm formation. In total, 10 flavonoids representing 4 major categories were screened and used in this study. The antioxidant capacity of each flavonoid was evaluated through a DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. Rutin showed the highest level of free radical scavenging capacity, followed by kaempferol, luteolin, quercetin, apigenin, hesperidin, sinensetin, naringenin, naringin and 3,5,6,7,8,3',4'-heptamethoxyflavone. The inhibitory effects of rutin and naringin on bacterial growth were also compared. The lowest MICs of rutin were found against K. pneumoniae ATCC700603 (1024 µg/mL) and E. coli ATCC25922 (512 µg/mL). However, the MBICs were not found. Rutin showed strong inhibitory ability against both the growth curve and biofilm production. The expression profiles of 15 biofilm-related genes were analyzed in biofilm cells both with and without rutin treatment. The luxS gene and wabG gene were downregulated significantly by rutin treatment. Correlation analysis showed that mrkA gene expression was positively correlated with biofilm biomass accumulation. Our study indicated that biofilm production is correlated with the expression of several genes rather than one. MrkA gene expression was positively correlated with biofilm biomass accumulation. Our study screened rutin as a potential agent to inhibit K. pneumoniae biofilm formation.


Assuntos
Antioxidantes , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Escherichia coli , Flavonoides/farmacologia , Humanos , Rutina/farmacologia
10.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361741

RESUMO

Due to their richness of bioactive substances, rose hips are a valuable raw material for obtaining extracts with potential antimicrobial activity. The aim of the study was to determine the antagonistic potential of whole pseudo-fruit and flesh extracts of three Rosa sp. varieties against Staphylococcus spp. bacteria isolated as food contaminants. The biological material in this study consisted of seven strains of bacteria from the genus Staphylococcus. Two strains-Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis DSMZ 3270-were used as reference strains. The other five strains were food-derived isolates-S. epidermidis A5, S. xylosus M5, S. haemolyticus M6, S. capitis KR6, and S. warneri KR2A. The material was the pseudo-fruits of Rosa canina, Rosa pomifera Karpatia, and Rosa rugosa. The polyphenols were extracted from the fleshy part and the whole pseudo-fruit for all rose varieties. The tested preparations differed significantly in their polyphenol composition. The sum of polyphenols ranged from 28 862 to 35 358 mg/100 g of lyophilisate. The main groups of polyphenols found in the preparations were flavanols and ellagitannins. All of the tested extracts inhibited the growth of staphylococci at a concentration of 500 mg/mL. Rosa rugosa fruit extract showed the strongest antimicrobial properties among the studied extracts. For all the strains, the growth inhibition had a diameter of 20.3-29.0 mm. Moreover, six out of the seven tested strains showed the highest inhibition with the use of this extract. The MIC of rose extracts was in the range of 3.125-500 mg/mL and was strictly dependent on the bacterial species, the species of the rose, and the part of the fruit from which the extract was obtained. Correlations were assessed between the main groups of polyphenols in the extracts and their inhibition of bacterial growth. In the case of pseudo-fruit extracts, the inhibitory effect on bacterial growth positively correlated with the content of ellagitannins, and this effect was observed for almost all the tested strains. The results presented herein follow the current trend of minimising the use of chemical preservatives in food; from this point of view, rose extracts are very promising.


Assuntos
Antibacterianos/química , Flavonoides/química , Taninos Hidrolisáveis/química , Polifenóis/química , Rosa/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Contaminação de Alimentos/prevenção & controle , Microbiologia de Alimentos/métodos , Frutas/química , Humanos , Taninos Hidrolisáveis/isolamento & purificação , Taninos Hidrolisáveis/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Staphylococcus/efeitos dos fármacos , Staphylococcus/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus capitis/efeitos dos fármacos , Staphylococcus capitis/crescimento & desenvolvimento , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/crescimento & desenvolvimento , Staphylococcus haemolyticus/efeitos dos fármacos , Staphylococcus haemolyticus/crescimento & desenvolvimento
11.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361744

RESUMO

Korean red pine (Pinus densiflora) belongs to the Genus Pinus, and its bark contains a great amount of naturally occurring phenolic compounds. Until now, few studies have been conducted to assess the neuroprotective effects of Pinus densiflora bark extract against brain ischemic injury. The aim of this study was to investigate the neuroprotective effects of pre-treatment with the extract in the hippocampus following 5-min transient forebrain ischemia in gerbils. Furthermore, this study examined the anti-inflammatory effect as a neuroprotective mechanism of the extract. Pinus densiflora bark was extracted by pure water (100 °C), and this extract was quantitatively analyzed and contained abundant polyphenols, flavonoids, and proanthocyanidins. The extract (25, 50, and 100 mg/kg) was orally administered once a day for seven days before the ischemia. In the gerbil hippocampus, death of the pyramidal neurons was found in the subfield cornu ammonis 1 (CA1) five days after the ischemia. This death was significantly attenuated by pre-treatment with 100 mg/kg, not 25 or 50 mg/kg, of the extract. The treatment with 100 mg/kg of the extract markedly inhibited the activation of microglia (microgliosis) and significantly decreased the expression of pro-inflammatory cytokines (interleukin 1ß and tumor necrosis factor α). In addition, the treatment significantly increased anti-inflammatory cytokines (interleukin 4 and interleukin 13). Taken together, this study clearly indicates that pre-treatment with 100 mg/kg of Pinus densiflora bark extract in gerbils can exert neuroprotection against brain ischemic injury by the attenuation of neuroinflammatory responses.


Assuntos
Anti-Inflamatórios/farmacologia , Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pinus/química , Prosencéfalo/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Flavonoides/química , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Gerbillinae , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação , Interleucina-13/agonistas , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-4/agonistas , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Fármacos Neuroprotetores/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Proantocianidinas/química , Proantocianidinas/farmacologia , Prosencéfalo/metabolismo , Prosencéfalo/patologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
12.
Phytochemistry ; 191: 112895, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34403885

RESUMO

Prenylated flavonoids, a unique class of flavonoids which combine a flavonoid skeleton and a lipophilic prenyl side-chain, possess great potential biological activities including cytotoxicity, anti-inflammation, anti-Alzheimer, anti-microbial, anti-oxidant, anti-diabetes, estrogenic, vasorelaxant and enzyme inhibition. Recently, prenylated flavonoids have become an indispensable anchor for the development of new therapeutic agents, and have received increasing from medicinal chemists. The prenylated flavonoids have been outstanding developed through isolation, semi or fully synthesis in a very short period of time, which proves the great value in medicinal chemistry researches. In this review, research progress of prenylated flavonoids including natural prenylated flavonoids, structural modification, synthetic methodologies and pharmacological activities was summarized comprehensively. Furthermore, the structure-activity relationships (SARs) of prenylated flavonoids were summarized which provided a basis for the selective design and optimization of multifunctional prenylated flavonoid derivatives for the treatment of multi-factorial diseases in clinic.


Assuntos
Antioxidantes , Flavonoides , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Prenilação , Relação Estrutura-Atividade
13.
Arch Oral Biol ; 130: 105219, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34364169

RESUMO

OBJECTIVE: The aim of this study was to investigate the role and molecular regulatory mechanisms of baicalin in oral squamous cell carcinoma (OSCC) progression. DESIGN: Gene expression in OSCC cells was detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). OSCC cell viability, migration, invasion and stemness were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), wound healing, Transwell, and sphere formation assays. The target genes of miR-106b-5p were predicted using bioinformatic tools. The interaction between microRNA-miR-106b-5p (miR-106b-5p) and disabled homolog 2 (DAB2) was confirmed by a luciferase reporter assay. TOP/FOP-Flash reporter assay and western blot analysis were used to analyze the activity of the Wnt/ß-catenin pathway. RESULTS: Baicalin inhibited OSCC cell viability, migration, invasion, and stemness. Baicalin downregulated miR-106b-5p expression. In addition, MiR-106b-5p upregulation reversed the effects of baicalin on OSCC cells. As a target gene of miR-106b-5p, DAB2 was negatively regulated by miR-106b-5p and upregulated by baicalin in OSCC cells. MiR-106b-5p activated Wnt/ß-catenin pathway in OSCC cells by inhibiting DAB2. Baicalin suppressed Wnt/ß-catenin pathway by upregulating DAB2. In rescue assays, miR-106b-5p overexpression-induced promotion of OSCC cellular processes was attenuated by DAB2 upregulation. CONCLUSIONS: Baicalin exerts anti-tumor effects in OSCC by inhibiting the miR-106b-5p-Wnt/ß-catenin pathway via upregulating DAB2.


Assuntos
Carcinoma de Células Escamosas , Flavonoides/farmacologia , MicroRNAs , Neoplasias Bucais , Via de Sinalização Wnt , Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
14.
Nutrients ; 13(8)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34444856

RESUMO

With a yearly production of about 39 million tons, brewer's spent grain (BSG) is the most abundant brewing industry byproduct. Because it is rich in fiber and protein, it is commonly used as cattle feed but could also be used within the human diet. Additionally, it contains many bioactive substances such as hydroxycinnamic acids that are known to be antioxidants and potent inhibitors of enzymes of glucose metabolism. Therefore, our study aim was to prepare different extracts-A1-A7 (solid-liquid extraction with 60% acetone); HE1-HE6 (alkaline hydrolysis followed by ethyl acetate extraction) and HA1-HA3 (60% acetone extraction of alkaline residue)-from various BSGs which were characterized for their total phenolic (TPC) and total flavonoid (TFC) contents, before conducting in vitro studies on their effects on the glucose metabolism enzymes α-amylase, α-glucosidase, dipeptidyl peptidase IV (DPP IV), and glycogen phosphorylase α (GPα). Depending on the extraction procedures, TPCs ranged from 20-350 µg gallic acid equivalents/mg extract and TFCs were as high as 94 µg catechin equivalents/mg extract. Strong inhibition of glucose metabolism enzymes was also observed: the IC50 values for α-glucosidase inhibition ranged from 67.4 ± 8.1 µg/mL to 268.1 ± 29.4 µg/mL, for DPP IV inhibition they ranged from 290.6 ± 97.4 to 778.4 ± 95.5 µg/mL and for GPα enzyme inhibition from 12.6 ± 1.1 to 261 ± 6 µg/mL. However, the extracts did not strongly inhibit α-amylase. In general, the A extracts from solid-liquid extraction with 60% acetone showed stronger inhibitory potential towards a-glucosidase and GPα than other extracts whereby no correlation with TPC or TFC were observed. Additionally, DPP IV was mainly inhibited by HE extracts but the effect was not of biological relevance. Our results show that BSG is a potent source of α-glucosidase and GPα inhibitors, but further research is needed to identify these bioactive compounds within BSG extracts focusing on extracts from solid-liquid extraction with 60% acetone.


Assuntos
Grão Comestível/química , Inibidores Enzimáticos/farmacologia , Glucose/metabolismo , Glicosídeo Hidrolases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Flavonoides/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Humanos , Fenóis/farmacologia
15.
Life Sci ; 283: 119864, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358548

RESUMO

AIMS: The study examined that morin as possible antioxidant and neuroprotective due to oxidative stress (H2O2) in zebrafish larval model. MATERIALS AND METHODS: Zebrafish larvae were induced with oxidative stress using H2O2 at 1 mM; their behavioural changes were assessed through partition preference and horizontal compartment test. The head section without eyes and yolk sac of zebrafish larvae were employed for enzyme assays such as SOD, CAT, Thiobarbituric acid reactive substances assay, reduced glutathione, glutathione peroxidase activity, glutathione S transferase, Acetylcholinesterase activity and nitrate levels. Also, intracellular ROS and apoptosis in larval head was detected by DCFDA and acridine orange staining followed by gene expression studies. KEY FINDINGS: Morin exposure was not harmful to the larvae at concentration between 20 and 60 µM, but it caused non-lethal deformity between 80 and 100 µM. In the partition test, zebrafish embryos treated with H2O2 showed cognitive impairment, whereas the morin-treated groups showed an improved behavioural activity. The study also found that restoring antioxidant enzymes and reduced lipid peroxidation which had a neuroprotective impact. Inhibition of NO overproduction and increased AChE activity were also shown to reduce the neuronal damage. Apoptosis and intracellular ROS levels were reduced in larvae when it was co-incubated with morin. Morin treatment up regulated the antioxidant enzymes against oxidative stress. SIGNIFICANCE: Morin provides protection against H2O2 induced oxidative stress through a cellular antioxidant defence mechanism by up-regulating gene expression, thus increasing the antioxidant activity at cellular or organismal stage.


Assuntos
Antioxidantes/farmacologia , Embrião não Mamífero/metabolismo , Flavonoides/farmacologia , Síndromes Neurotóxicas , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero/patologia , Peróxido de Hidrogênio/efeitos adversos , Peróxido de Hidrogênio/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/embriologia , Síndromes Neurotóxicas/patologia
16.
Biomolecules ; 11(8)2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34439920

RESUMO

In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The disease has been associated with high mortality rate, especially in patients with comorbidities such as diabetes, cardiovascular and kidney diseases. This could be attributed to dysregulated immune responses and severe systemic inflammation in COVID-19 patients. The use of effective antiviral drugs against SARS-CoV-2 and modulation of the immune responses could be a potential therapeutic strategy for COVID-19. Studies have shown that natural phenolic compounds have several pharmacological properties, including anticoronavirus and immunomodulatory activities. Therefore, this review discusses the dual action of these natural products from the perspective of applicability at COVID-19.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Flavonoides/uso terapêutico , Fatores Imunológicos/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Inibidores de Proteases/uso terapêutico , Animais , Antivirais/química , Antivirais/farmacologia , Coronavirus/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia
17.
Molecules ; 26(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34443698

RESUMO

There are tens of thousands of scientific papers about flavonoids and their impacts on human health. However, despite the vast amount of energy that has been put toward studying these compounds, a unified molecular mechanism that explains their bioactivity remains elusive. One contributing factor to the absence of a general mechanistic explanation of their bioactivity is the complexity of flavonoid chemistry in aqueous solutions at neutral pH. Flavonoids have acidic protons, are redox active, and frequently auto-oxidize to produce an array of degradation products including electrophilic quinones. Flavonoids are also known to interact with specificity and high affinity with a variety of proteins, and there is evidence that some of these interactions may be covalent. This review summarizes the mechanisms of flavonoid oxidation in aqueous solutions at neutral pH and proposes the formation of protein-flavonoid adducts or flavonoid-induced protein oxidation as putative mechanisms of flavonoid bioactivity in cells. Nucleophilic residues in proteins may be able to form covalent bonds with flavonoid quinones; alternatively, specific amino acid residues such as cysteine, methionine, or tyrosine in proteins could be oxidized by flavonoids. In either case, these protein-flavonoid interactions would likely occur at specific binding sites and the formation of these types of products could effectively explain how flavonoids modify proteins in cells to induce downstream biochemical and cellular changes.


Assuntos
Flavonoides/farmacologia , Proteínas/metabolismo , Animais , Flavonoides/química , Humanos , Modelos Moleculares , Oxirredução , Soluções
18.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445697

RESUMO

Polyphenols, such as flavonoids and phenolic acids, are a group of specialized metabolites in plants that largely aid in plant defense by deterring biotic stressors and alleviating abiotic stress. Polyphenols offer a wide range of medical applications, acting as preventative and active treatments for diseases such as cancers and diabetes. Recently, researchers have proposed that polyphenols may contribute to certain applications aimed at tackling challenges related to the COVID-19 pandemic. Understanding the beneficial impacts of phytochemicals, such as polyphenols, could potentially help prepare society for future pandemics. Thus far, most reviews have focused on polyphenols in cancer prevention and treatment. This review aims to provide a comprehensive discussion on the critical roles that polyphenols play in both plant chemical defense and human health based on the most recent studies while highlighting prospective avenues for future research, as well as the implications for phytochemical-based applications in both agricultural and medical fields.


Assuntos
Plantas/metabolismo , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antivirais/farmacologia , Disponibilidade Biológica , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Hidroxibenzoatos/farmacologia , Hipoglicemiantes/farmacologia , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos , Plantas/química , Polifenóis/metabolismo , Estudos Prospectivos , SARS-CoV-2/efeitos dos fármacos
19.
J Agric Food Chem ; 69(35): 10138-10150, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34459191

RESUMO

Dietary flavonoids are known to have anti-inflammatory and anticancer effects, but their influences on human macrophage migration inhibitory factor (MIF), a vital proinflammatory cytokine recognized as a therapeutic target for infectious diseases and cancers, have been rarely reported. Here, we identified 24 dietary flavonoids that could inhibit the tautomerase activity of MIF, five of which exerted IC50 values lower than the positive control ISO-1 in the micromolar range: morin (IC50 = 11.01 ± 0.45 µM) and amentoflavone (IC50 = 13.32 ± 0.64 µM) exhibited the most potent efficacy followed by apigenin (IC50 = 42.74 ± 4.20 µM), naringin (IC50 = 51.38 ± 2.12 µM), and fisetin (IC50 = 51.99 ± 0.63 µM). X-ray crystallography, molecular docking, and cellular experiments were utilized to illustrate the molecular binding details and structure-activity relationships. Scaffold modifications of flavonoids significantly influenced the potency. What stands out for morin is the unique 2'-OH substitution. In addition, amentoflavone situated at the MIF trimer pore may impact MIF-CD74 signaling. The results also showed that flavonoids could suppress cell chemotaxis and nitric oxide production in RAW264.7 cells. Our results elucidate the molecular mechanism of flavonoids acting on MIF and shed light on developing lead compounds against MIF-involved diseases.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Anti-Inflamatórios/farmacologia , Flavonoides/farmacologia , Humanos , Oxirredutases Intramoleculares , Fatores Inibidores da Migração de Macrófagos/genética , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
20.
Molecules ; 26(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34443463

RESUMO

In our study, Allium subhirsutum L. (AS) was investigated to assess its phenolic profile and bioactive molecules including flavonoids and organosulfur compounds. The antioxidant potential of AS and wound healing activity were addressed using skin wound healing and oxidative stress and inflammation marker estimation in rat models. Phytochemical and antiradical activities of AS extract (ASE) and oil (ASO) were studied. The rats were randomly assigned to four groups: group I served as a control and was treated with simple ointment base, group II was treated with ASE ointment, group III was treated with ASO ointment and group IV (reference group; Ref) was treated with a reference drug "Cytolcentella® cream". Phytochemical screening showed that total phenols (215 ± 3.5 mg GAE/g) and flavonoids (172.4 ± 3.1 mg QE/g) were higher in the ASO than the ASE group. The results of the antioxidant properties showed that ASO exhibited the highest DPPH free radical scavenging potential (IC50 = 0.136 ± 0.07 mg/mL), FRAP test (IC50 = 0.013 ± 0.006 mg/mL), ABTS test (IC50 = 0.52 ± 0.03 mg/mL) and total antioxidant capacity (IC50 = 0.34 ± 0.06 mg/mL). In the wound healing study, topical application of ASO performed the fastest wound-repairing process estimated by a chromatic study, percentage wound closure, fibrinogen level and oxidative damage status, as compared to ASE, the Cytolcentella reference drug and the untreated rats. The use of AS extract and oil were also associated with the attenuation of oxidative stress damage in the wound-healing treated rats. Overall, the results provided that AS, particularly ASO, has a potential medicinal value to act as effective skin wound healing agent.


Assuntos
Allium/química , Antioxidantes/farmacologia , Dermatite/tratamento farmacológico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Fibrinogênio/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Tecido de Granulação/efeitos dos fármacos , Masculino , Fenóis/farmacologia , Fenóis/uso terapêutico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Óleos Vegetais/uso terapêutico , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...