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1.
Chem Biol Drug Des ; 103(4): e14520, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570710

RESUMO

Quercetin, a bioactive natural compound renowned for its potent anti-inflammatory, antioxidant, and antiviral properties, has exhibited therapeutic potential in various diseases. Given that bronchopulmonary dysplasia (BPD) development is closely linked to inflammation and oxidative stress, and quercetin, a robust antioxidant known to activate NRF2 and influence the ferroptosis pathway, offers promise for a wide range of age groups. Nonetheless, the specific role of quercetin in BPD remains largely unexplored. This study aims to uncover the target role of quercetin in BPD through a combination of network pharmacology, molecular docking, computer analyses, and experimental evaluations.


Assuntos
Displasia Broncopulmonar , Ferroptose , Hiperóxia , Animais , Recém-Nascido , Humanos , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/metabolismo , Hiperóxia/tratamento farmacológico , Hiperóxia/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Simulação de Acoplamento Molecular , Ciclo-Oxigenase 2 , Animais Recém-Nascidos , Antioxidantes , Farmacologia em Rede
2.
PLoS One ; 19(4): e0301519, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38578751

RESUMO

Rice blast disease, caused by the fungus Magnaporthe oryzae, poses a severe threat to rice production, particularly in Asia where rice is a staple food. Concerns over fungicide resistance and environmental impact have sparked interest in exploring natural fungicides as potential alternatives. This study aimed to identify highly potent natural fungicides against M. oryzae to combat rice blast disease, using advanced molecular dynamics techniques. Four key proteins (CATALASE PEROXIDASES 2, HYBRID PKS-NRPS SYNTHETASE TAS1, MANGANESE LIPOXYGENASE, and PRE-MRNA-SPLICING FACTOR CEF1) involved in M. oryzae's infection process were identified. A list of 30 plant metabolites with documented antifungal properties was compiled for evaluation as potential fungicides. Molecular docking studies revealed that 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin exhibited superior binding affinities compared to reference fungicides (Azoxystrobin and Tricyclazole). High throughput molecular dynamics simulations were performed, analyzing parameters like RMSD, RMSF, Rg, SASA, hydrogen bonds, contact analysis, Gibbs free energy, and cluster analysis. The results revealed stable interactions between the selected metabolites and the target proteins, involving important hydrogen bonds and contacts. The SwissADME server analysis indicated that the metabolites possess fungicide properties, making them effective and safe fungicides with low toxicity to the environment and living beings. Additionally, bioactivity assays confirmed their biological activity as nuclear receptor ligands and enzyme inhibitors. Overall, this study offers valuable insights into potential natural fungicides for combating rice blast disease, with 2-Coumaroylquinic acid, Myricetin, Rosmarinic Acid, and Quercetin standing out as promising and environmentally friendly alternatives to conventional fungicides. These findings have significant implications for developing crop protection strategies and enhancing global food security, particularly in rice-dependent regions.


Assuntos
Ascomicetos , Fungicidas Industriais , Magnaporthe , Oryza , Ácido Quínico/análogos & derivados , Antifúngicos/farmacologia , Fungicidas Industriais/farmacologia , Quercetina/farmacologia , Simulação de Acoplamento Molecular , Oryza/microbiologia , Flavonoides/farmacologia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia
3.
J Vet Sci ; 25(2): e30, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38568831

RESUMO

BACKGROUND: Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. OBJECTIVES: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,O-carboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. METHODS: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. RESULTS: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis. In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. CONCLUSIONS: This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.


Assuntos
Quitosana , Nanopartículas , Animais , Staphylococcus epidermidis/genética , Nanogéis , Gelatina/farmacologia , Quercetina/farmacologia , Biofilmes , Quitosana/farmacologia , Quitosana/química , Gelatinases/farmacologia , Antibacterianos/farmacologia
4.
BMC Vet Res ; 20(1): 134, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570774

RESUMO

BACKGROUND: Porcine acute diarrhea syndrome coronavirus (SADS-CoV) is one of the novel pathogens responsible for piglet diarrhea, contributing to substantial economic losses in the farming sector. The broad host range of SADS-CoV raises concerns regarding its potential for cross-species transmission. Currently, there are no effective means of preventing or treating SADS-CoV infection, underscoring the urgent need for identifying efficient antiviral drugs. This study focuses on evaluating quercetin as an antiviral agent against SADS-CoV. RESULTS: In vitro experiments showed that quercetin inhibited SADS-CoV proliferation in a concentration-dependent manner, targeting the adsorption and replication stages of the viral life cycle. Furthermore, quercetin disrupts the regulation of the P53 gene by the virus and inhibits host cell cycle progression induced by SADS-CoV infection. In vivo experiments revealed that quercetin effectively alleviated the clinical symptoms and intestinal pathological damage caused by SADS-CoV-infected piglets, leading to reduced expression levels of inflammatory factors such as TLR3, IL-6, IL-8, and TNF-α. CONCLUSIONS: Therefore, this study provides compelling evidence that quercetin has great potential and promising applications for anti- SADS-CoV action.


Assuntos
Alphacoronavirus , Infecções por Coronavirus , Coronavirus , Doenças dos Suínos , Suínos , Animais , Coronavirus/genética , Quercetina/farmacologia , Quercetina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/veterinária , Diarreia/veterinária , Doenças dos Suínos/tratamento farmacológico
5.
Chem Biol Interact ; 393: 110939, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38490643

RESUMO

Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc. Oxidative stress levels, mitochondrial function and endothelial barrier changes were observed in vitro by using DCFH-DA probe detection, flow cytometry, JC-1 probe, immunofluorescence and the establishment in vitro BLB models, etc. QU pretreatment activates the PI3K/AKT signaling pathway, inhibits CDDP-induced oxidative stress, protects mitochondrial function, and reduces mitochondrial apoptosis in PCs. However, PI3K/AKT specific inhibitor (LY294002) partially reverses the protective effects of QU. In addition, in vitro BLB models were established by coculturing PCs and endothelial cells (ECs), which suggests that QU both reduces the CDDP-induced apoptosis in PCs and improves the endothelial barrier permeability. On the whole, the research findings suggest that QU can be used as a novel treatment to reduce CDDP-induced ototoxicity.


Assuntos
Cisplatino , Ototoxicidade , Camundongos , Animais , Masculino , Cisplatino/farmacologia , Cisplatino/metabolismo , Pericitos/metabolismo , Quercetina/farmacologia , Quercetina/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células Endoteliais/metabolismo , Ototoxicidade/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Apoptose
6.
J Cancer Res Ther ; 20(1): 261-267, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38554331

RESUMO

BACKGROUND AND OBJECTIVE: Radiation therapy is a routine clinical practice that has been used for a long time in the treatment of cancer patients. The most important dose-limiting organ in patients receiving radiotherapy for various conditions is the brain. The mechanisms underlying brain and pituitary gland damage caused by radiation are largely unknown. It is of great importance to use radioprotective agents to protect against damage. This study aims to evaluate the neuroprotective effects of quercetin in experimental radiation-induced brain and pituitary gland damage. MATERIALS AND METHODS: A total of 60 adult male Wistar-albino rats were randomly divided into six groups (control, sham, radiation, quercetin, radiation + quercetin, and quercetin + radiation groups, with ten rats in each group). Quercetin was given to rats by oral gavage at 50 mg/kg/day. A whole-body single dose of 10 Gy radiation was applied to the rats. Tissue samples belonging to the groups were compared after excision. Histopathological changes in the brain tissue and pituitary gland were examined with hematoxylin-tissue samples in the groups and compared histologically and immunohistochemically. RESULTS: The histopathological examination of the brain and anterior pituitary gland sections showed marked damage in the radiation-treated rats, while the quercetin-administered groups showed normal tissue architecture. While neuropeptid Y immunoreactivity was increased, synaptophysin immunoreactivity was decreased in the brains of radiation-treated rats. However, when neuropeptide Y and synaptophysin expression were assessed in the anterior pituitary gland, there was no significant difference between the groups. CONCLUSION: Consequently, quercetin may be a potential pharmacological agent in modulating radiation-induced damage in rats. However, extra experimental and preclinical studies are needed to confirm our findings before they can be used clinically.


Assuntos
Fármacos Neuroprotetores , Quercetina , Humanos , Ratos , Masculino , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Raios gama/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Sinaptofisina , Ratos Wistar , Estresse Oxidativo , Antioxidantes/farmacologia
7.
Eur J Pharmacol ; 970: 176491, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38503399

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease with the hallmark of aggregation of beta-amyloid (Aß) into extracellular fibrillar deposition. Accumulating evidence suggests that soluble toxic Aß oligomers exert diverse roles in neuronal cell death, oxidative stress, neuroinflammation, and the eventual pathogenesis of AD. Aß is derived from the sequential cleavage of amyloid-ß precursor protein (APP) by ß-secretase (BACE1) and γ-secretase. The current effect of single targeting is not ideal for the treatment of AD. Therefore, developing multipotent agents with multiple properties, including anti-Aß generation and anti-Aß aggregation, is attracting more attention for AD treatment. Previous studies indicated that Quercetin was able to attenuate the effects of several pathogenetic factors in AD. Here, we showed that naturally synthesized Quercetin-3-O-glc-1-3-rham-1-6-glucoside (YCC31) could inhibit Aß production by reducing ß-secretase activity. Further investigations indicated that YCC31 could suppress toxic Aß oligomer formation by directly binding to Aß. Moreover, YCC31 could attenuate Aß-mediated neuronal death, ROS and NO production, and pro-inflammatory cytokines release. Taken together, YCC31 targeting multiple pathogenetic factors deserves further investigation for drug development of AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Secretases da Proteína Precursora do Amiloide/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Citocinas , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Glucosídeos/uso terapêutico
8.
J Mol Histol ; 55(2): 211-225, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38441713

RESUMO

Quercetin has been documented to possess a multitude of pharmacological effects, encompassing antioxidant, antiviral, antimicrobial, and anti-inflammatory properties. Nevertheless, the exact molecular mechanisms responsible for the anti-tumor properties of quercetin remain to be fully explicated. To this end, quercetin was administered to gastric cancer cells (in vitro) AGS and MKN45, as well as BALB/c mice (in vivo). The proliferation ability of cells was evaluated using cholecystokinin octapeptide (CCK-8) and colony formation assays. The evaluation of ferroptosis involved the measurement of iron, malondialdehyde (MDA), and lipid reactive oxygen species. Autophagy and apoptosis were evaluated using immunofluorescence staining, western blotting, and flow cytometry analysis. Our findings indicate that quercetin significantly inhibited cell viability and tumor volume compared to the control group. Additionally, quercetin was found to decrease glutathione (GSH), malondialdehyde, and reactive oxygen species (ROS) levels while suppressing beclin1 and LC3B levels in cancer cells. Remarkably, the utilization of siATG5 was found to reverse all the aforementioned effects of quercetin. Ultimately, the effects of quercetin on gastric cancer were validated. In summary, our findings provide evidence that quercetin facilitates autophagy-mediated ferroptosis in gastric cancer.


Assuntos
Ferroptose , Neoplasias Gástricas , Animais , Camundongos , Espécies Reativas de Oxigênio , Quercetina/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Autofagia , Malondialdeído
9.
Life Sci ; 344: 122561, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38490298

RESUMO

AIMS: Increasing evidence suggests a link between gut microbial dysbiosis and the pathogenesis of depression. Alpha-glycosyl isoquercitrin (AGIQ), consisting of isoquercitrin and its glycosylated quercetin, has beneficial effects on the gut microbiome and brain function. Here, we detected the potential antidepressant impact of a four-week administration of AGIQ and its underlying mechanisms using a mouse model of depression. MAIN METHODS: Male C57BL/6 mice were orally administered AGIQ (0.05 % or 0.5 % in drinking water) for 28 days; subchronic social defeat stress was performed in the last 10 days. Behavior tests were conducted to assess anxiety and depressive-like behaviors. Additionally, evaluations encompassed 5-hydroxytryptamine (5-HT) levels, the gut microbiota composition, lipopolysaccharide (LPS) concentrations, short-chain fatty acids levels, and intestinal barrier integrity changes. KEY FINDINGS: AGIQ significantly alleviated depression-like behaviors and increased hippocampal 5-HT levels. Further, AGIQ mitigated stress-induced gut microbial abnormalities and reduced the levels of LPS in the serum, which affected the relative gene expression levels of 5-HT biosynthesis enzymes in vitro. Furthermore, AGIQ reversed the reduced butyrate levels in cecal contents and improved the impaired intestinal barrier by increasing the expression of colonic zonula occluden-1 (ZO-1) and occludin, thereby decreasing LPS leakage. SIGNIFICANCE: Our results suggest that AGIQ could improve stress-induced depression by regulating the gut microbiome, which inhibits LPS production and maintains the gut barrier. This is the first report on the potential effect of AGIQ on depression via the gut microbiota-brain axis, shedding new light on treatment options.


Assuntos
Eixo Encéfalo-Intestino , Quercetina , Quercetina/análogos & derivados , Animais , Camundongos , Masculino , Quercetina/farmacologia , Depressão/tratamento farmacológico , Lipopolissacarídeos , Derrota Social , Serotonina , Camundongos Endogâmicos C57BL
10.
Neurosci Lett ; 826: 137730, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38485080

RESUMO

PURPOSE: Considering that the combination of dasatinib and quercetin (D + Q) demonstrated a neuroprotective action, as well as that females experience a decline in hormonal levels during aging and this is linked to increased susceptibility to Alzheimer's disease, in this study we evaluated the effect of D + Q on inflammatory and oxidative stress markers and on acetylcholinesterase and Na+, K+-ATPase activities in brain of female mice. METHODS: Female C57BL/6 mice were divided in Control and D (5 mg/kg) + Q (50 mg/kg) treated. Treatment was administered via gavage for three consecutive days every two weeks starting at 30 days of age. The animals were euthanized at 6 months of age and at 14 months of age. RESULTS: Results indicate an increase in reactive species (RS), thiol content and lipid peroxidation followed by a reduction in nitrite levels and superoxide dismutase, catalase and glutathione S-transferase activity in the brain of control animals with age. D+Q protected against age-associated increase in RS and catalase activity reduction. Acetylcholinesterase activity was increased, while Na+, K+-ATPase activity was reduced at 14 months of age and D+Q prevented this reduction. CONCLUSION: These data demonstrate that D+Q can protect against age-associated neurochemical alterations in the female brain.


Assuntos
Acetilcolinesterase , Senoterapia , Ratos , Feminino , Camundongos , Animais , Catalase/metabolismo , Acetilcolinesterase/metabolismo , Ratos Wistar , Camundongos Endogâmicos C57BL , Antioxidantes/farmacologia , Estresse Oxidativo , Quercetina/farmacologia , Encéfalo/metabolismo , Superóxido Dismutase/metabolismo , Adenosina Trifosfatases
11.
Pol Merkur Lekarski ; 52(1): 17-22, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38518228

RESUMO

OBJECTIVE: Aim: To study the general activity of NO synthases (gNOS), the activity of inducible and constitutive isoforms of NO synthase, the activity of arginases, and the concentration of nitrites in the nasal mucosa under the conditions of local treatment of chronic atrophic rhinitis (AR) with quercetin and platelet-rich plasma (PRP therapy).. PATIENTS AND METHODS: Materials and Methods: The study was conducted on 118 patients divided into two groups: control (n=20) and experimental (patients with AR, n=98). Experimental group was divided into 4 subgroups: standard treatment (n=29), PRP therapy (6 injections for 28 day course, n=19), Quercetin (40 mg 3 times a day for 28 days, n=26) and PRP+Quercetin (n=24) groups. RESULTS: Results: Standard therapy of SaR increases gNOS by 278.38% and arginase activity increases by 222.73%. PRP therapy increases gNOS by 211.43% and arginase by 540.91%. Quercetin elevates gNOS by 108.33% and arginase by 250%. PRP therapy and quercetin increases gNOS by 146.15% and arginase by 536.36%. CONCLUSION: Conclusions: The use of standard therapy of SaR and addition of PRP therapy, quercetin and their combination effectively restores the production of nitric oxide and the arginase activity in the nasal mucosa.


Assuntos
Rinite Atrófica , Humanos , Óxido Nítrico , Quercetina/farmacologia , Quercetina/uso terapêutico , Arginase , Mucosa Nasal , Óxido Nítrico Sintase
12.
Mol Biol Rep ; 51(1): 445, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38520487

RESUMO

BACKGROUND: Inflammation is an important factor contributing to obesity-induced metabolic disorders. Different investigations confirm that local inflammation in adipose issues is the primary reason for such disorder, resulting in low-grade systemic inflammation. Anti-inflammatory, antioxidant, and epigenetic modification are among the varied properties of Quercetin (QCT) as a natural flavonoid. OBJECTIVE: The precise molecular mechanism followed by QCT to alleviate inflammation has been unclear. This study explores whether the anti-inflammatory effects of QCT in 3T3-L1 differentiated adipocytes may rely on SIRT-1. METHODS: The authors isolated 3T3-L1 pre-adipocyte cells and exposed them to varying concentrations of QCT, lipopolysaccharide (LPS), and a selective inhibitor of silent mating type information regulation 2 homolog 1 (SIRT-1) called EX-527. After determining the optimal dosages of QCT, LPS, and EX-527, they assessed the mRNA expression levels of IL-18, IL-1, IL-6, TNF-α, SIRT-1, and adiponectin using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: The study showed considerable cytotoxic effects of LPS (200 ng/mL) + QCT (100 µM) + EX-527 (10 µM) on 3T3-L1 differentiated adipocytes after 48 h of incubation. QCT significantly upregulated the expression levels of adiponectin and SIRT-1 (p < 0.0001). However, introducing SIRT-1 inhibitor (p < 0.0001) reversed the impact of QCT on adiponectin expression. Additionally, QCT reduced SIRT-1-dependent pro-inflammatory cytokines in 3T3-L1 differentiated adipocytes (p < 0.0001). CONCLUSION: This study revealed that QCT treatment reduced crucial pro-inflammatory cytokines levels and increased adiponectin levels following LPS treatment. This finding implies that SIRT-1 may be a crucial factor for the anti-inflammatory activity of QCT.


Assuntos
Adiponectina , Lipopolissacarídeos , Animais , Camundongos , Humanos , Adiponectina/genética , Adiponectina/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Quercetina/farmacologia , Quercetina/metabolismo , Células 3T3-L1 , Adipócitos/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo
13.
Sci Rep ; 14(1): 6286, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491064

RESUMO

The major risk factor for chronic disease is chronological age, and age-related chronic diseases account for the majority of deaths worldwide. Targeting senescent cells that accumulate in disease-related tissues presents a strategy to reduce disease burden and to increase healthspan. The senolytic combination of the tyrosine-kinase inhibitor dasatinib and the flavonol quercetin is frequently used in clinical trials aiming to eliminate senescent cells. Here, our goal was to computationally identify natural senotherapeutic repurposing candidates that may substitute dasatinib based on their similarity in gene expression effects. The natural senolytic piperlongumine (a compound found in long pepper), and the natural senomorphics parthenolide, phloretin and curcumin (found in various edible plants) were identified as potential substitutes of dasatinib. The gene expression changes underlying the repositioning highlight apoptosis-related genes and pathways. The four compounds, and in particular the top-runner piperlongumine, may be combined with quercetin to obtain natural formulas emulating the dasatinib + quercetin formula.


Assuntos
Quercetina , Senoterapia , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Quercetina/farmacologia , Quercetina/uso terapêutico , Senescência Celular , Expressão Gênica
14.
Respir Res ; 25(1): 120, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468259

RESUMO

BACKGROUND: Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression. METHODS: COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression. RESULTS: Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-ß (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment. CONCLUSIONS: These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Quercetina , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Quercetina/metabolismo , Interleucina-8/metabolismo , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/farmacologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/genética , Brônquios/metabolismo , Células Epiteliais/metabolismo , Células Cultivadas , Fatores de Transcrição/metabolismo , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/farmacologia
15.
Biomed Pharmacother ; 173: 116418, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38461683

RESUMO

Quercetin is a representative flavonoid that is widely present in fruits, herbs, and vegetables. It is also an important active core component in traditional Chinese medicines. As an important flavonoid, quercetin has various properties and exerts antioxidant, anti-inflammatory, and cardioprotective effects. The public interest in quercetin is increasing, and quercetin has been used to prevent or treat numerous of diseases, such as polycystic ovary syndrome (PCOS), cancer, autoimmune diseases and chronic cardiovascular diseases, in clinical experiments and animal studies due to its powerful antioxidant properties and minimal side effects. Quercetin exerts marked pharmacological effects on gynecological disorders; however, there have been no reviews about the potential health benefits of quercetin in the context of gynecological disorders, including PCOS, premature ovary failure (POF), endometriosis (EM), ovarian cancer (OC), cervical cancer (CC) and endometrial carcinoma (EC). Thus, this review aimed to summarize the biological effects of quercetin on gynecological disorders and its mechanisms.


Assuntos
Síndrome do Ovário Policístico , Quercetina , Humanos , Animais , Feminino , Quercetina/farmacologia , Quercetina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Flavonoides/uso terapêutico
16.
Cell Mol Biol (Noisy-le-grand) ; 70(2): 257-263, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38430013

RESUMO

Granulosa cells are somatic cells located inside follicles that play a crucial role in the growth and development of follicles. Quercetin and tanshinone are two key monomers in traditional Chinese medicine that have antioxidant and anti-aging properties. The KGN cell apoptosis model caused by triptolide (TP) was employed in this work to investigate granulosa cell death and medication rescue. Quercetin and tanshinone therapy suppressed KGN cell death and oxidation while also regulating the expression of critical apoptosis and oxidation-related markers such as B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax). Further research revealed that the effects of Quercetin and Tanshinone were accomplished via deacetylation of FOXO3A in the cytoplasm and mitochondria via the SIRT1/SIRT3-FOXO3a axis. In summary, Quercetin and tanshinone protect KGN cells from apoptosis by reducing mitochondrial apoptosis and oxidation via the SIRT1/SIRT3-FOXO3a axis.


Assuntos
Abietanos , Sirtuína 3 , Feminino , Humanos , Apoptose , Autofagia/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Quercetina/farmacologia , Sirtuína 1/efeitos dos fármacos , Sirtuína 1/metabolismo , Sirtuína 3/efeitos dos fármacos , Sirtuína 3/metabolismo , Proteína Forkhead Box O3/efeitos dos fármacos
17.
Biomed Res Int ; 2024: 7632408, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38456097

RESUMO

Despite tremendous advances in the prevention and treatment of infectious diseases, only few antiparasitic drugs have been developed to date. Protozoan infections such as malaria, leishmaniasis, and trypanosomiasis continue to exact an enormous toll on public health worldwide, underscoring the need to discover novel antiprotozoan drugs. Recently, there has been an explosion of research into the antiprotozoan properties of quercetin, one of the most abundant flavonoids in the human diet. In this review, we tried to consolidate the current knowledge on the antiprotozoal effects of quercetin and to provide the most fruitful avenues for future research. Quercetin exerts potent antiprotozoan activity against a broad spectrum of pathogens such as Leishmania spp., Trypanosoma spp., Plasmodium spp., Cryptosporidium spp., Trichomonas spp., and Toxoplasma gondii. In addition to its immunomodulatory roles, quercetin disrupts mitochondrial function, induces apoptotic/necrotic cell death, impairs iron uptake, inhibits multiple enzymes involved in fatty acid synthesis and the glycolytic pathways, suppresses the activity of DNA topoisomerases, and downregulates the expression of various heat shock proteins in these pathogens. In vivo studies also show that quercetin is effective in reducing parasitic loads, histopathological damage, and mortality in animals. Future research should focus on designing effective drug delivery systems to increase the oral bioavailability of quercetin. Incorporating quercetin into various nanocarrier systems would be a promising approach to manage localized cutaneous infections. Nevertheless, clinical trials are needed to validate the efficacy of quercetin in treating various protozoan infections.


Assuntos
Criptosporidiose , Cryptosporidium , Infecções por Protozoários , Humanos , Animais , Quercetina/farmacologia , Quercetina/uso terapêutico , Compostos Fitoquímicos/uso terapêutico
18.
Cancer Med ; 13(4): e7082, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38457248

RESUMO

BACKGROUND: Tumor metastasis and recurrence are major causes of mortality in patients with hepatocellular carcinoma (HCC) that is still lack of effective therapeutic targets and drugs. Previous reports implied that ras homolog family member C (RhoC) plays a toxic role on metastasis and proliferation of cancer. METHODS: In this research, the correlation between RhoC and metastasis ability was confirmed by in vitro experiments and TCGA database. We explored whether quercetin could inhibit cell migration or invasion by transwell assay. Real-time PCR, overexpression and ubiquitination assay, etc. were applied in mechanism study. Primary HCC cells and animal models including patient-derived xenografts (PDXs) were employed to evaluate the anti-metastasis effects of quercetin. RESULTS: Clinical relevance and in vitro experiments further confirmed the level of RhoC was positively correlated with invasion and metastasis ability of HCC. Then we uncovered that quercetin could attenuate invasion and metastasis of HCC by downregulating RhoC's level in vitro, in vivo and PDXs. Furthermore, mechanistic investigations displayed quercetin hindered the E3 ligase expression of SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) leading to enhancement of RhoC's ubiquitination and proteasomal degradation. CONCLUSIONS: Our research has revealed the novel mechanisms quercetin regulates degradation of RhoC level by targeting SMURF2 and identified quercetin may be a potential compound for HCC therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Quercetina/farmacologia , Invasividade Neoplásica/genética , Proteína de Ligação a GTP rhoC/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Ubiquitina-Proteína Ligases/metabolismo
19.
Org Biomol Chem ; 22(14): 2877-2890, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38525805

RESUMO

Oxidative stress and carbonyl stress resulting from the toxicity of small aldehydes are part of the detrimental mechanisms leading to neuronal cell loss involved in the progression of neurodegenerative diseases such as Alzheimer's disease. Polyunsaturated alkylated lipophenols represent a new class of hybrid molecules that combine the health benefits of anti-inflammatory omega-3 fatty acids with the anti-carbonyl and oxidative stress (anti-COS) properties of (poly)phenols in a single pharmacological entity. To investigate the therapeutic potential of quercetin-3-docosahexaenoic acid-7-isopropyl lipophenol in neurodegenerative diseases, three synthetic pathways using chemical or chemo-enzymatic strategies were developed to access milligram or gram scale quantities of this alkyl lipophenol. The protective effect of quercetin-3-DHA-7-iPr against cytotoxic concentrations of acrolein (a carbonyl stressor) was assessed in human SHSY-5Y neuroblastoma cells to underscore its ability to alleviate harmful mechanisms associated with carbonyl stress in the context of neurodegenerative diseases.


Assuntos
Ácidos Graxos Ômega-3 , Doenças Neurodegenerativas , Humanos , Quercetina/farmacologia , Estresse Oxidativo , Ácidos Graxos Ômega-3/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo
20.
Colloids Surf B Biointerfaces ; 237: 113837, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508086

RESUMO

Ultra Violet radiations induced skin damage and associated skin disorders are a widespread concern. The consequences of sun exposure include a plethora of dermal conditions like aging, solar urticaria, albinism and cancer. Sunscreens provide effective protection to skin from these damages. Besides FDA approved physical and chemical UV filters, phytoconstituents with their multi functionalities are emerging as frontrunners in Therapy of skin disorders. Objective of this study was to develop novel phyto-dermal gel (PDG) with dual action of sun protection and antioxidant potential using polymeric mixed micelles (PMMs) are nanocarriers. PMMs of Pluronic F127 and Pluronic F68 loaded with curcumin and quercetin were optimized by 32 factorial designs. Responses studied were vesicle size, SPF, entrapment efficiency of curcumin and quercetin and antioxidant activity. Droplet size ranged from 300 to 500 nm with PDI in between 0.248 and 0.584. Combination of curcumin and quercetin showed enhanced sun protection and antioxidant activity. Pluronics played a significant positive role in various parameters. In present studies vesicle size of factorial batches was found to be between 387 and 527 nm, and SPF was found to be between 18.86 and 28.32. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into Carbopol 940. Optimized PDG was evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and skin retention. Hysteresis loop in the rheogram suggested thixotropy of PDG. Syneresis for gels from day 0-30 days was found to be between 0% and 12.46% w/w. SPF of optimized PDG was 27±0.5. Optimized PDG showed no signs of erythema and edema on Wistar rats. PMMs thus effectively enhanced antioxidant and skin protective effect of curcumin and quercetin.


Assuntos
Cosmecêuticos , Curcumina , Ratos , Animais , Micelas , Curcumina/farmacologia , Curcumina/química , Antioxidantes/farmacologia , Quercetina/farmacologia , Ratos Wistar , Poloxâmero/química , Polímeros/química , Géis , Portadores de Fármacos/química , Tamanho da Partícula
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