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1.
Braz. j. biol ; 84: e252936, 2024. graf, ilus
Artigo em Inglês | VETINDEX | ID: biblio-1374648

RESUMO

Neutrophil extracellular traps (NETs) were first reported as a microbicidal strategy for activated neutrophils. Through an immunologic response against several stimuli, neutrophils release their DNA together with proteins from granules, nucleus, and cytoplasm (e.g., elastase and myeloperoxidase). To date, NETs have been implicated in tissue damage during intense inflammatory processes, mainly when their release is dependent on oxygen radical generation. Flavonoids are antioxidant and anti-inflammatory agents; of these, quercetin is commonly found in our daily diet. Therefore, quercetin could exert some protective activity against tissue damage induced by NETs. In our in vitro assays, quercetin reduced NETs, myeloperoxidase (MPO), and elastase release from neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA). The activity of these enzymes also decreased in the presence of quercetin. Quercetin also reduced the cytotoxic effect of NETs on alveolar cells (A549 cell line). Further, in silico assays indicated favorable interactions between quercetin and NET proteins (MPO and elastase). Overall, our results demonstrate that quercetin decreases deleterious cellular effects of NETs by reducing their release from activated neutrophils, and diminishing the enzymatic activity of MPO and elastase, possibly through direct interaction.


As armadilhas extracelulares de neutrófilos (NETs) foram relatadas pela primeira vez como uma estratégia microbicida para neutrófilos ativados. Por meio de uma resposta imunológica contra vários estímulos, os neutrófilos liberam seu DNA ligado a proteínas de grânulos, núcleo e citoplasma (por exemplo, elastase e mieloperoxidase). Até o momento, os NETs têm sido implicadas em danos aos tecidos durante processos inflamatórios intensos, principalmente quando sua liberação depende da geração de radicais de oxigênio. Os flavonóides são agentes antioxidantes e anti-inflamatórios, e destes, a quercetina é comumente encontrada em nossa dieta diária. Portanto, a quercetina pode exercer alguma atividade protetora contra o dano tecidual induzido por NETs. Em nossos ensaios in vitro, a quercetina reduziu a liberação das NETs, mieloperoxidase (MPO) e elastase a partir de neutrófilos estimulados com forbol 12-miristato 13-acetato (PMA). A atividade dessas enzimas também foi diminuída na presença de quercetina. A quercetina também reduziu o efeito citotóxico dos NETs sobre células alveolares (linha celular A549). Além disso, os ensaios in silico indicaram interações favoráveis entre a quercetina e as proteínas da NET (MPO e elastase). No geral, nossos resultados demonstram que a quercetina diminui os efeitos deletérios das NETs, reduzindo sua liberação à partir de neutrófilos ativados e diminuindo a atividade enzimática de MPO e elastase, possivelmente por meio de interação direta.


Assuntos
Quercetina , Flavonoides , Armadilhas Extracelulares , Imunidade , Anti-Inflamatórios , Neutrófilos , Antioxidantes
2.
Molecules ; 28(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36677632

RESUMO

Sepsis is a serious health concern globally, which necessitates understanding the root cause of infection for the prevention of proliferation inside the host's body. Phytochemicals present in plants exhibit antibacterial and anti-proliferative properties stipulated for sepsis treatment. The aim of the study was to determine the potential role of Carica papaya leaf extract for sepsis treatment in silico and in vitro. We selected two phytochemical compounds, carpaine and quercetin, and docked them with bacterial proteins, heat shock protein (PDB ID: 4PO2), surfactant protein D (PDB ID: 1PW9), and lactobacillus bacterial protein (PDB ID: 4MKS) against imipenem and cyclophosphamide. Quercetin showed the strongest interaction with 1PW9 and 4MKS proteins. The leaves were extracted using ethanol, methanol, and water through Soxhlet extraction. Total flavonoid content, DPPH assay, HPTLC, and FTIR were performed. In vitro cytotoxicity of ethanol extract was screened via MTT assay on the J774 cell line. Ethanol extract (EE) possessed the maximum number of phytocomponents, the highest amount of flavonoid content, and the maximum antioxidant activity compared to other extracts. FTIR analysis confirmed the presence of N-H, O-H, C-H, C=O, C=C, and C-Cl functional groups in ethanol extract. Cell viability was highest (100%) at 25 µg/mL of EE. The present study demonstrated that the papaya leaves possessed antibacterial and cytotoxic activity against sepsis infection.


Assuntos
Carica , Sepse , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteínas de Bactérias , Carica/química , Simulação de Acoplamento Molecular , Quercetina , Antibacterianos/farmacologia , Compostos Fitoquímicos/análise , Flavonoides , Etanol , Sepse/tratamento farmacológico , Folhas de Planta/química
3.
Molecules ; 28(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36677770

RESUMO

Propolis is a resinous compound made by bees with well-known biological activity. However, comparisons between encapsulated and non-encapsulated propolis are lacking. Therefore, the antibacterial activity, effect on the phase transition of lipids, and inhibition of UV-induced lipid oxidation of the two forms of propolis were compared. The results showed that non-encapsulated propolis produces quicker effects, thus being better suited when more immediate effects are required (e.g., antibacterial activity). In order to gain an in-depth introspective on these effects, we further studied the synergistic effect of propolis compounds on the integrity of lipid membranes. The knowledge of component synergism is important for the understanding of effective propolis pathways and for the perspective of modes of action of synergism between different polyphenols in various extracts. Thus, five representative molecules, all previously isolated from propolis (chrysin, quercetin, trans-ferulic acid, caffeic acid, (-)-epigallocatechin-3-gallate) were mixed, and their synergistic effects on lipid bilayers were investigated, mainly using DSC. The results showed that some compounds (quercetin, chrysin) exhibit synergism, whereas others (caffeic acid, t-ferulic acid) do not show any such effects. The results also showed that the synergistic effects of mixtures composed from several different compounds are extremely complex to study, and that their prediction requires further modeling approaches.


Assuntos
Própole , Própole/farmacologia , Quercetina/farmacologia , Flavonoides/farmacologia , Bactérias , Antibacterianos/farmacologia , Lipídeos
4.
Sci Rep ; 13(1): 1237, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36690753

RESUMO

Aflatoxin M2 (AFM2) is a type of mycotoxin detected in milk or dairy products from animals consuming contaminated feed. In this study, the toxicity mechanism of AFM2 and the protective effects of quercetin were investigated in albino mice. For this purpose, the mice were divided into 6 groups and the groups were fed with quercetin and AFM2. The toxic effects of AFM2 and the protective properties of quercetin were investigated using physiological, biochemical and cytogenetic parameters. The genotoxic mechanism of AFM2 and the protective role of quercetin were investigated by molecular docking, which is an in silico model. As a result, 16 mg/kg b.w AFM2 administration caused serious changes in body weight, organ index, kidney and liver weight, and deterioration of antioxidant/oxidant balance in liver and kidney organs. The decrease in glutathione levels along with an increase in malondialdehyde (MDA) levels in the liver and kidney after AFM2 administration indicates that oxidative stress is induced. The increases in alanine transaminase (ALT) and aspartat transaminase (AST) levels, which are indicators of liver damage, and the increases in serum levels of blood urea nitrogen (BUN) and creatinine, which are indicators of kidney damage, confirm the damage in both organs. AFM2 also caused genotoxicity by inducing micronucleus (MN) and chromosomal abnormalities (CAs) in bone marrow tissue. It has been determined that AFM2, which exhibits genotoxicity as a result of its clastogenic and aneugenic effects, causes CAs by interacting with DNA. Quercetin provided significant protection by improving liver and kidney tissues, partial normalization in serum parameter levels, and severe reductions in MN and CAs. The highest protection was determined as 74.1% against dicentric chromosome formations in 50 mg/kg b.w quercetin application. The interaction of quercetin with xanthine oxidase and nitric oxide synthase enzymes was determined in silico with an inhibition constant in the range of 283.71-476.17 nM. These interactions cause changes in the activity of enzymes, reducing the oxidative load in the cell, and in this way, quercetin provides protection. All toxic effects induced by AFM2 were decreased with quercetin administration dose-dependently, and this protective effect was associated with quercetin's reduction of oxidative load by inhibiting the free radical-producing enzyme. All toxic effects caused by AFM2 were decreased with quercetin administration in a dose-dependent manner, and this protective effect was associated with quercetin's reduction of oxidative load by inhibiting the enzyme that produces free radicals.


Assuntos
Antioxidantes , Quercetina , Camundongos , Animais , Quercetina/farmacologia , Simulação de Acoplamento Molecular , Antioxidantes/metabolismo , Estresse Oxidativo , Glutationa/metabolismo , Rim/metabolismo , Fígado/metabolismo , Malondialdeído/metabolismo
5.
Lasers Med Sci ; 38(1): 49, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36689023

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the dose-dependent side effects of cisplatin. The loss of sensory neurons is observed in CIPN. There are many methods to minimalize CIPN symptoms such as pharmacological agents and photobiostimulation but the mechanisms of these methods are unclear. Our study is aimed at determining the effects of quercetin and low-level laser therapy (LLLT) in undifferentiated and nerve growth factor-differentiated PC12 cells in cisplatin-induced peripheral neuropathy. PC12 cells with cisplatin were co-treated with quercetin and LLLT (diode pumped all-solid-state laser, 670 nm, output 500 mW, and the laser beam surface area was 1.96 cm2). The effects of quercetin and LLLT on GAP-43 and Synapsin I expressions were analyzed by real-time PCR, cell viability was assessed by MTT assay, Annexin and dead assay measured the induction of apoptosis, the alterations in mitopotential were assessed by mitopotential assay, and lactate dehydrogenase activity in cells was analyzed. All experiment data were analyzed by the Tukey test and applied as a post hoc test, and statistical evaluation was made. Our results indicated that cisplatin increased apoptosis (24,210 ± 2189, 46,504 ± 8246) cells, mitochondrial dysfunction (44,312 ± 0.751, 68,788 ± 1271), and LDH activity (62,821 ± 8245, 87,838 ± 8116). Furthermore, it decreased cell viability (42,447 ± 1780, 36,140 ± 3682) and inhibited GAP-43 and Synapsin I genes in undifferentiated and differentiated PC12 cells. However, apoptosis, the alterations in mitopotential, and lactate dehydrogenase activity decreased by applications of quercetin and LLLT. It has been recommended that quercetin and low-level laser therapy roles on cisplatin-induced peripheral neuropathy should be investigated in vivo, and the relationship between quercetin and low-level laser therapy should be molecular.


Assuntos
Antineoplásicos , Terapia com Luz de Baixa Intensidade , Doenças do Sistema Nervoso Periférico , Ratos , Animais , Cisplatino/efeitos adversos , Quercetina/efeitos adversos , Terapia com Luz de Baixa Intensidade/métodos , Proteína GAP-43 , Sinapsinas , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Lactato Desidrogenases , Antineoplásicos/farmacologia
6.
Anal Chim Acta ; 1239: 340706, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36628714

RESUMO

The appearance of multi-drug resistant Escherichia coli makes the combination of tetracyclines (TCs) and quercetin (QCT) more common to fight stubborn bacterial infections so that the effective detections of TCs and QCT are essential and necessary. Here, a novel fluorescence probe for differentiating TCs and QCT is developed based on the nitrogen and copper co-doped carbon dots (N, Cu-CDs). The N, Cu-CDs are prepared from ethylene diamine tetraacetic acid (EDTA) and anhydrous copper chloride as precursors through hydrothermal process and exhibit bright blue fluorescence with excellent optical stability. With the presence of four tetracyclines (DOX, TC, CTC and OTC), the fluorescence intensity of N, Cu-CDs is quenched directly due to the internal filtration effect (IFE), and the detection limit obtained through single-signal fluorescence sensing is as low as 23.8 nM for DOX, 37.2 nM for TC, 43.8 nM for OTC and 28.8 nM for CTC. More remarkably, three dimensional ratiometric fluorescence probe for detecting QCT is proposed based on the appearance of another emission at (410 nm, 490 nm) due to electron transform (ET) process. This new method shows a good linear relationship in the range of 10-100 µM with a low detection limit of 59.3 nM. Furthermore, a dual-channel fluorescence sensing platform based on microfluidics paper-based analytical devices (µPADs) is developed for simultaneously visual discrimination of TCs (DOX is chosen as the typical detecting model for TCs) and QCT. This investigation provides a new way for the development of CDs as multifunction fluorescence probes.


Assuntos
Pontos Quânticos , Tetraciclinas , Espectrometria de Fluorescência/métodos , Quercetina , Carbono , Cobre , Antibacterianos , Corantes Fluorescentes , Transferência de Energia
7.
Food Res Int ; 163: 112293, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596197

RESUMO

Nature-derived chemicals have recently gained increased attention to settle down the challenges in the food industry. Quercetin has long been used as a natural medicine but its photoactivity has been neglected. In this work, by combining photodynamic bacteria inactivation (PDI) with an edible coating (Pectin/Quercetin) derived from FDA-approved chemicals, extend shelf-life and protected commercial quality of fresh-cut apples were achieved. Firstly, the potential photoactivated antibacterial performance of Quercetin (a natural plant flavonoid) was clarified with the treatment of a simulated sunlight lamp, realizing antibacterial efficacy of 100 % towards S. aureus (50 min) and L. monocytogenes (80 min) with light treatment. To develop safe and effective preservation of fresh-cut apples, Pectin/Quercetin edible coatings with 100 µmol/L quercetin were adopted. The results showed that the prepared edible coatings form a protective barrier over the surface of apples, effectively resisting bacterial infection and extending shelf life to 10 days while maintaining good commercial quality (including preferable color, keeping 100 % hardness, 80 % sugar content and 17.3 % weightlessness rate). Therefore, the prepared light-driven Pectin/Quercetin in this work has the potential to develop as fresh-cut fruit preservation technology.


Assuntos
Filmes Comestíveis , Malus , Malus/microbiologia , Conservação de Alimentos/métodos , Quercetina/farmacologia , Staphylococcus aureus , Compostos Fitoquímicos , Pectinas , Antibacterianos
8.
Molecules ; 28(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36615550

RESUMO

Red onion wastes (ROW) are valuable sources of bioactive metabolites with promising antimicrobial effects. Methicillin-resistant Staphylococcus aureus (MRSA) infections are a growing risk in hospitals and communities. This study aims to investigate the in vitro and in vivo antibiofilm activities of the acidified ethanolic extract of red onion scales (RO-T) and its fractions against an MRSA vaginal colonization model. The RO-T extract, as well as its anthocyanin-rich fraction (RO-P) and flavonoid-rich fraction (RO-S), recorded a promising antibacterial activity against highly virulent strains of bacteria (MRSA, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa). RO-S showed the highest antibacterial activity (MBC of 0.33 ± 0.11 mg/mL) against MRSA USA300 and significantly eradicated its biofilm formation with an IC50 of 0.003. Using a rat model, in vivo assessment on all samples, which were formulated as a hydrogel, revealed a significant reduction of MRSA bacterial load recovered from an infected vagina compared to that of the negative control group (NCG). RO-T extract and vancomycin groups recorded the highest antibacterial activity with a bacterial load 2.998 and 3.358 logs lower than the NCG, respectively. The histopathological investigation confirmed our findings. RO-T and RO-S were standardized for their quercetin content. Finally, ROW offers a new potent antibiofilm agent mostly due to its high quercetin content.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Eliminação de Resíduos , Feminino , Ratos , Animais , Cebolas , Alimentos , Quercetina/farmacologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Escherichia coli , Biofilmes
9.
Molecules ; 28(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36615626

RESUMO

Recent evidences indicate that there is a substantial increase in worldwide cases of dementia. Alzheimer's disease is the leading cause of dementia and may contribute to 60-70% of cases. Quercetin is a unique bioflavonoid that has numerous therapeutic benefits such as anti-allergy, anti-ulcer, anti-inflammatory, anti-hypertensive, anti-cancer, immuno-modulatory, anti-infective, antioxidant, acetylcholinesterase inhibitory activity, neuroprotective effects, etc. In the present study, we evaluated the neuroprotective effect of orally administered quercetin with memantine in albino Wistar rats after inducing neurotoxicity through AlCl3 (100 mg/kg, p.o.). Chronic administration of AlCl3 resulted in poor retention of memory and significant oxidative damage. Various behavioral parameters, such as locomotor activity, Morris water maze, elevated plus maze, and passive avoidance test, were assessed on days 21 and 42 of the study. The animals were euthanatized following the completion of the last behavioral assessment. Various oxidative stress parameters were assessed to know the extent of oxidative damage to brain tissue. Quercetin with memantine has shown significant improvement in behavioral studies, inhibition of AChE activity, and reduction in oxidative stress parameters. Histopathological studies assessed for cortex and hippocampus using hematoxylin and eosin (H&E), and Congo red stain demonstrated a reduction in amyloid-ß plaque formation after treatment of quercetin with memantine. Immunohistochemistry showed that quercetin with memantine treatment also improved the expression of brain-derived neurotrophic factor (BDNF) and inhibited amyloid-ß plaque formation. The present study results demonstrated protective effects of treatment of quercetin with memantine in the neurotoxicity linked to aluminum chloride in albino Wistar rats.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Ratos , Animais , Fármacos Neuroprotetores/uso terapêutico , Ratos Wistar , Memantina/farmacologia , Quercetina/farmacologia , Compostos de Alumínio/toxicidade , Cloretos/toxicidade , Acetilcolinesterase/metabolismo , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Estresse Oxidativo , Aprendizagem em Labirinto
10.
J Orthop Surg Res ; 18(1): 21, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624462

RESUMO

BACKGROUND: Liuwei Dihuang Pill (LP) was verified to alleviate postmenopausal osteoporosis (PMOP) development. Nevertheless, the major constituent of LP and the related network pharmacology study remain unexplored. METHODS: Protein-protein interaction was established to identify the downstream target of LP in PMOP, and the related signaling pathway was investigated by bioinformatics analysis. MC3T3-E1 cells were added to ferric ammonium citrate (FAC) to mimic osteoporosis in vitro. The osteoblasts were identified by Alizarin red staining. Western blot was applied to evaluate protein levels. In addition, Cell Counting Kit-8 (CCK8) assay was applied to assess cell viability, and cell apoptosis was assessed by flow cytometry. RESULTS: Quercetin was the major constituent of LP. In addition, quercetin significantly reversed FAC-induced inhibition of osteogenic differentiation in MC3T3-E1 cells. In addition, quercetin notably abolished the FAC-induced upregulation of Bax, Caspase-3, FOS, JUN, TGFB1 and PPARD. In contrast, Bcl-2, p-mTOR/mTOR, p-AKT/AKT and p-PI3K/PI3K levels in MC3T3-E1 cells were reduced by FAC, which was restored by quercetin. Meanwhile, FAC notably inhibited the viability of MC3T3-E1 cells via inducing apoptosis, but this impact was abolished by quercetin. Furthermore, quercetin could reverse pcDNA3.1-FOS-mediated growth of FAC-treated osteoblasts by mediating PI3K/AKT/mTOR signaling. CONCLUSION: Quercetin alleviated the progression of PMOP via activation of PI3K/AKT/mTOR signaling. Hence, this study would shed novel insights into discovering new methods against PMOP.


Assuntos
Osteoporose Pós-Menopausa , Proteínas Proto-Oncogênicas c-akt , Quercetina , Feminino , Linhagem Celular , Farmacologia em Rede , Osteoblastos/metabolismo , Osteogênese , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Camundongos
11.
Sci Rep ; 13(1): 510, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627363

RESUMO

Anxiety is one of the most prevalent forms of psychopathology that affects millions worldwide. It gained more importance under the pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/benefit ratio resulting in a shift toward active ingredients with better safety profile such as the naturally occurring quercetin (QRC). The delivery of QRC is hampered by its low water solubility and low bioavailability. The potential to enhance QRC delivery to the brain utilizing polymeric nanocapsules administered intranasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best formula displayed a particle size of 227.8 ± 11.9 nm, polydispersity index of 0.466 ± 0.023, zeta potential of - 17.5 ± 0.01 mV, and encapsulation efficiency % of 92.5 ± 1.9%. In vitro release of QRC loaded polymeric nanocapsules exhibited a biphasic release with an initial burst release followed by a sustained release pattern. Behavioral testing demonstrated the superiority of QRC loaded polymeric nanocapsules administered intranasally compared to QRC dispersion administered both orally and intranasally. The prepared QRC loaded polymeric nanocapsules also demonstrated good safety profile with high tolerability.


Assuntos
Nanocápsulas , Quercetina , Polímeros , Benzodiazepinas , Ansiedade/tratamento farmacológico , Tamanho da Partícula
12.
Cells ; 12(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36611972

RESUMO

Oral squamous cell carcinoma (OSCC) frequently carries high epidermal growth factor receptor (EGFR) expression. Erlotinib, a small molecule tyrosine kinase inhibitor (TKI), is an effective inhibitor of EGFR activity; however, resistance to this drug can occur, limiting therapeutic outcomes. Therefore, in the current study, we aimed to unveil key intracellular molecules and adjuvant reagents to overcome erlotinib resistance. First, two HSC-3-derived erlotinib-resistant cell lines, ERL-R5 and ERL-R10, were established; both exhibited relatively higher growth rates, glucose utilization, epithelial-mesenchymal transition (EMT), and invasiveness compared with parental cells. Cancer aggressiveness-related proteins, such as N-cadherin, Vimentin, Twist, MMP-2, MMP-9, and MMP-13, and the glycolytic enzymes PKM2 and GLUT1 were upregulated in ERL-R cells. Notably, ERL-R cells were sensitive to quercetin, a naturally-existing flavonol phytochemical with anti-cancer properties against various cancer cells. At a concentration of 5 µM, quercetin effectively arrested cell growth, reduced glucose utilization, and inhibited cellular invasiveness. An ERL-R5-derived xenograft mouse model confirmed the growth-inhibitory efficacy of quercetin. Additionally, knock-down of PKM2 by siRNA mimicked the effect of quercetin and re-sensitized ERL-R cells to erlotinib. Furthermore, adding quercetin blocked the development of erlotinib-mediated resistance by enhancing apoptosis. In conclusion, our data support the application of quercetin in anti-erlotinib-resistant OSCC and indicate that PKM2 is a determinant factor in erlotinib resistance and quercetin sensitivity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Pulmonares , Neoplasias Bucais , Humanos , Animais , Camundongos , Cloridrato de Erlotinib/farmacologia , Cloridrato de Erlotinib/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Quercetina/farmacologia , Quercetina/uso terapêutico , Piruvato Quinase , Neoplasias Pulmonares/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral , Neoplasias Bucais/tratamento farmacológico , Receptores ErbB/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Glucose
13.
Eur J Med Chem ; 247: 115075, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36599228

RESUMO

The ß-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for the suppression of hyperactive Wnt/ß-catenin signaling that is vigorously involved in cancer initiation and development. Herein, we first described quercetin and its derivatives had potential inhibitory effects on ß-catenin/BCL9 PPI. The most potent compound, quercetin-3'-O-(4-methylpiperazine-1-yl) propyl (C1), directly binded with ß-catenin and disrupted the ß-catenin/BCL9 interaction in both the protein level and the cellular context. C1 also effectively inhibited colorectal cancer in vitro and showed better selectivity in inhibiting hyperactive Wnt/ß-catenin signaling cells like CT26 and HCT116. And we further confirmed that C1 could inhibit CT26 tumor growth in vivo and regulate the tumor immune microenvironment. This study provides a good chemical probe to explore ß-catenin-related biology and a drug-like quercetin derivative as novel ß-catenin/BCL9 PPI inhibitors for further drug development.


Assuntos
Quercetina , beta Catenina , beta Catenina/metabolismo , Quercetina/farmacologia , Proteínas de Neoplasias/metabolismo , Linhagem Celular Tumoral , Via de Sinalização Wnt
14.
Life Sci ; 314: 121343, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36592787

RESUMO

AIM: Intrahepatic cholestasis is a common pathological condition of several types of liver disorders. In this study, we aimed to investigate the regulatory effects of quercetin (QU) on selected phosphodiesterase inhibitors against alpha-naphthyl isothiocyanate (ANIT)-induced acute intrahepatic cholestasis. METHODS: Cholestasis was induced in Wistar albino rats by ANIT as a single dose (60 mg/kg; P·O.). QU (50 mg/kg, daily, P·O.), sildenafil (Sild; 10 mg/kg, twice daily, P·O.), and pentoxifylline (PTX; 50 mg/kg, daily, P.O.) were evaluated either alone or in combinations for 10 days for their antioxidant, anti-inflammatory, and anti-pyroptotic effects. RESULTS: ANIT produced a prominent intrahepatic cholestasis as evidenced by a significant alteration in liver functions, histological structure, inflammatory response, and oxidative stress biomarkers. Furthermore, up-regulation of NF-κB-p65, TLR4, NLRP3, cleaved caspase-1, IKK-ß, and IL-1ß concurrently with down-regulation of Nrf-2, HO-1, and PPAR-γ expressions were observed after ANIT. QU, Sild, or PTX treatment significantly alleviated the disturbance induced by ANIT. These findings were further supported by the improvement in histopathological features. Additionally, co-administration of QU with Sild or PTX significantly improved liver defects due to ANIT as compared to the individual drugs. SIGNIFICANCE: Combined QU with Sild or PTX exhibited promising hepatoprotective effects and anti-cholestatic properties through modulation of Nrf2/ARE, TLR4/NF- κB, and NLRP3/IL-1ß signaling pathways.


Assuntos
Colestase Intra-Hepática , Colestase , Pentoxifilina , Humanos , NF-kappa B/metabolismo , Fígado/metabolismo , Quercetina/uso terapêutico , Pentoxifilina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Citrato de Sildenafila/farmacologia , Citrato de Sildenafila/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Receptor 4 Toll-Like/metabolismo , Colestase Intra-Hepática/induzido quimicamente , Colestase/metabolismo , Transdução de Sinais
15.
Medicine (Baltimore) ; 102(2): e32623, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637916

RESUMO

To explore the mechanism of Xiaoqinglong decoction (XQLD) in the treatment of infantile asthma (IA) based on network pharmacology and molecular docking. The active ingredients of fdrugs in XQLD were retrieved from Traditional Chinese Medicine Systems Pharmacology database and then the targets of drug ingredients were screened. The disease targets of IA were obtained from OMIM and Gencards databases, and the intersection targets of XQLD in the treatment of IA were obtained by Venny 2.1 mapping of ingredient targets and disease targets. Cytoscape software was used to construct active ingredient-intersection target network. The potential targets of XQLD in the treatment of IA were analyzed by protein-protein interaction network using STRING platform, and the Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were obtained by R Studio software. AutoDock was used to perform molecular docking for verification. In this study, 150 active ingredients of XQLD were obtained, including quercetin, kaempferol, ß-sitosterol, luteolin, stigmasterol, and so on. And 92 intersection targets of drugs and diseases were obtained, including interleukin 6 (IL6), cystatin 3, estrogen receptor 1, hypoxia inducible factor 1A, HSP90AA1, epidermal growth factor receptor and so on. There were 127 items of Gene Ontology enrichment analysis and 125 Kyoto Encyclopedia of Genes and Genomes enrichment results, showing that apoptosis, IL-17 signaling pathway, tumor necrosis factor signaling pathway, P13K-Akt signaling pathway and other pathways may play a key role in the treatment of IA by XQLD. The results of molecular docking showed that the key active ingredients including quercetin, kaempferol, ß-sitosterol, luteolin, stigmasterol, and the core targets including IL6, cystatin 3, estrogen receptor 1, hypoxia inducible factor 1A, HSP90AA1, and epidermal growth factor receptor had good binding activity. Through network pharmacology and molecular docking, the potential targets and modern biological mechanisms of XQLD in the treatment of IA were preliminarily revealed in the study, which will provide reference for subsequent animal experiments and clinical trials.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Animais , Simulação de Acoplamento Molecular , Cistatina C , Receptor alfa de Estrogênio , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Farmacologia em Rede , Interleucina-6 , Luteolina , Quercetina , Estigmasterol , Receptores ErbB , Asma/tratamento farmacológico , Hipóxia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa
16.
Braz. J. Biol. ; 83: 1-7, 2023. graf, ilus
Artigo em Inglês | VETINDEX | ID: vti-765501

RESUMO

Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.(AU)


O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.(AU)


Assuntos
Humanos , Neoplasias Colorretais/tratamento farmacológico , Quercetina/administração & dosagem , Apoptose/efeitos dos fármacos , Catequina/administração & dosagem , Anexina A5/uso terapêutico
17.
Behav Brain Res ; 440: 114260, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36535433

RESUMO

Excessive physical exercise (overtraining, OT) charactered by long-term and excessive training results in the damage of multiple vital tissues including hippocampus which plays a critical role in learning and memory. A combination of dasatinib (D) plus quercetin (Q) (D+Q) belongs to senolytic drugs which selectively kill senescent cells in vitro and vivo. In this study, the rats that suffered a five-week excessive swimming training were subjected to the oral administration of D+Q. D+Q alleviated the decline in exercise performance of OT rats during the swimming training, and prevented learning and memory deficits in Morris water maze, Y-maze and novel object recognition tests after excessive swimming training. Analytical results by SA-ß-gal staining and western blotting showed that D+Q significantly reduced senescent cells with repressed expression of senescence-related proteins, p53 and p21, in hippocampus. Nissl and immunohistochemical staining showed that D+Q significantly attenuated neuronal loss caused by apoptosis. Interestingly, we observed elevated level of cleaved caspase 3, an apoptosis executor protein, in p21 positive hippocampus cells by D+Q treatment in immunofluorescent staining, suggesting that senescent cells were induced to apoptosis in D+Q-treated rats. The positive control drug, silibinin, showed similar protective effect against OT, but did not induce the apoptosis of senescent cells, suggesting a difference in the protective mechanisms. These results indicated that D+Q alleviates overtraining-induced deficits in learning and memory through elimination of senescent cells and reduction of apoptotic cell number.


Assuntos
Apoptose , Quercetina , Ratos , Animais , Quercetina/farmacologia , Dasatinibe/farmacologia , Dasatinibe/metabolismo , Aprendizagem em Labirinto , Senescência Celular , Hipocampo/metabolismo
18.
Food Chem ; 409: 135270, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-36580701

RESUMO

Nanoliposome is an effective delivery system for polyphenols, whereas it always suffers from low electrostatic stability and oxidation of lipid membranes. Here, different charged anionic polysaccharides including carrageenan (-62.67 ± 1.85 mV), trehalose (-20.73 ± 1.42 mV), and pectin (-4.47 ± 0.38 mV) were used as coating material to improve the stability of nanoliposomes. Results showed that carrageenan coating greatly inhibited aggregation and fusion of nanoliposome. The coating of the higher charged polysaccharides produced the more hydrogen bonds and made the inner chains of lipid molecules more compact, thus improving the rigidity of the membrane and thermal stability. In addition, the polysaccharide coating effectively reduced the lateral diffusion within the membrane and the propagation rate of oxidation reaction. The aim of this study is to investigate the effect of anionic polysaccharides with different charges on coated nanoliposomes, provide reference for the delivery of quercetin.


Assuntos
Polissacarídeos , Quercetina , Carragenina/química , Polissacarídeos/química , Pectinas/química , Lipídeos
19.
Braz. j. biol ; 83: e248746, 2023. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1339351

RESUMO

Abstract Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.


Resumo O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.


Assuntos
Humanos , Neoplasias Colorretais/tratamento farmacológico , Catequina/análogos & derivados , Catequina/farmacologia , Quercetina/farmacologia , Ciclo Celular , Anexina A5 , Linhagem Celular Tumoral , Proliferação de Células
20.
Food Funct ; 14(1): 206-214, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36476928

RESUMO

L-Carnitine can be metabolized to trimethylamine (TMA) by gut microbiota and further converted into trimethylamine N-oxide (TMAO) in the liver, leading to liver damage. This study aimed to investigate the protective effect of quercetin against high L-carnitine-induced liver toxicity in mice. 3% L-carnitine drinking water was used to feed mice in this study. The formation of TMAO in the blood circulation of the tested mice was down-regulated following quercetin treatment. Administration of quercetin could also effectively antagonize the liver injury caused by high L-carnitine intake, which was proved by the decreased serum AST and ALT activities and the reduced levels of inflammatory liver cytokines (IL-1, IL-6, TNF-α, and TNF-ß). Moreover, quercetin exhibited a rebalancing effect on dyslipidemia (TC, TG, HDL, and LDL) and antioxidant abilities (SOD, GSH-Px, MDA, and RAHFR) in L-carnitine-treated mice. The results of hepatic H&E and Oil Red O staining further verified the liver injury of high L-carnitine-treated mice and the protective effects of quercetin. These findings suggested that quercetin could attenuate the hepatotoxic effects of the mice fed with a high L-carnitine diet via inhibiting the circulating TMAO formation.


Assuntos
Carnitina , Quercetina , Camundongos , Animais , Carnitina/metabolismo , Quercetina/farmacologia , Camundongos Endogâmicos C57BL , Metilaminas , Dieta , Óxidos
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