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OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.
Subject(s)
Chick Embryo , Animals , Quercetin/therapeutic use , Lipopolysaccharides/toxicity , Matrix Metalloproteinase 9 , Caspase 3 , Matrix Metalloproteinase 3 , Toll-Like Receptor 4 , Claudin-1 , Inflammation/metabolism , Apoptosis , RNA, Messenger , Autophagy , NF-kappa BABSTRACT
Heart failure is one of the main cardiovascular system diseases at present， and it is a clinical syndrome caused by changes in cardiac structure and function， resulting in impaired ejection function or ventricular filling. Therefore， heart failure has become the most important cardiovascular disease in the 21st century. In recent years， the incidence of heart failure is increasing， and the survival rate of patients with heart failure is very low. Traditional Chinese medicine has rich experience in preventing and treating heart failure. With the modernization of traditional Chinese medicine， more and more attention has been paid to the research， development， and application of active ingredients in traditional Chinese medicine. Traditional Chinese medicine has unique advantages in improving the heart function of patients with heart failure by treating multiple targets and multiple pathways through syndrome differentiation. Astragalus membranacus， a traditional Chinese medicine， is a kind of medicine that benefits Qi and blood circulation and removes evil spirits. It has the functions of improving myocardial energy metabolism and hemodynamics， protecting myocardial muscle， and promoting angiogenesis. Astragalus membranaceus is often used to treat patients with heart failure， yielding remarkable results. In recent years， it has been found that astragaloside， Astragalus polysaccharide， quercetin， calyx isoflavones， and other main active ingredients of Astragalus membranacus can improve cardiac function and treat heart failure by inhibiting inflammatory response， myocardial apoptosis， and myocardial fibrosis. This paper reviewed the research progress of the action and mechanism of the active ingredients of Astragalus membranacus in the treatment of heart failure by studying relevant literature， with a view to providing a reference for its further research， development， and application in the prevention and treatment of heart failure.
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To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL
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Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.
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Aim To study the mechanism of quereetin (Que) inhibiting mitochondrial damage induced by Aβ
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Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.
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OBJECTIVE To investigate the effects of quercetin on mitochondrial energy metabolism function after myocardial ischemia. METHODS H9c2 cells were divided into blank group， model group， quercetin high-dose， medium-dose and low-dose groups （40， 20， 10 μmol/L）， and positive control group （cyclosporine A， 1 μmol/L）. Reactive oxygen species （ROS）， mitochondrial membrane potential （MMP）， openness of mitochondrial permeability transition pore （MPTP）， adenosine triphosphate （ATP）， malondialdehyde （MDA）， lactate dehydrogenase （LDH） and creatine kinase （CK） were observed after cell hypoxia treatment. Rats were randomly assigned into sham operation group， model group， quercetin high-dose， medium-dose and low-dose groups （100， 50， 25 mg/kg）， and positive control group （trimetazidine， 6.3 mg/kg）， with 8 rats in each group. They were given relevant medicine intragastrically， once a day， for 7 consecutive days. After the last medication， myocardial ischemia model was induced by the ligation of the left anterior descending branch of the coronary artery. The contents of LDH， MDA， creatine kinase isoenzyme-MB （CK-MB）， superoxide dismutase （SOD）， complex Ⅰ， complex Ⅳ and ATP in serum were all determined. RESULTS Compared with the model group， ROS fluorescence intensity， openness of MPTP， the contents of CK， LDH and MDA were significantly decreased in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of MMP and ATP were all increased significantly （P＜0.01）； the contents of CK-MB， LDH and MDA in serum were all decreased significantly in quercetin low-dose， medium-dose and high-dose groups， and positive control group， while the contents of SOD， complex Ⅰ， complex Ⅳ and ATP （except for positive control group） were increased significantly （P＜ 0.05 or P＜0.01）. CONCLUSIONS Quercetin can effectively reduce myocardial hypoxic injury， promote endogenous energy production and improve mitochondrial function after myocardial ischemia.
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Introduction: Periodontitis is a pandemic, with about 14 percent of people worldwide already suffering from severe periodontitis. Early intervention in the disease could probably reduce its progression and eliminate the need for the extraction of affected teeth. Quercetin is a probable candidate as it has exemplary anti-inflammatory properties. The presence of phenolic hydroxyl groups in them greatly contributes to their antioxidant and anti-inflammatory activities. Objectives: The study introduces the formulation of Quercetin mouthwash and assesses its anti-inflammatory properties in comparison to Diclofenac sodium. Methods: Quercetin mouthwash was prepared using a commercially procured bioactive agent. One standard nonsteroidal anti-inflammatory drug, Diclofenac was used as a reference drug. The percentage inhibition of protein denaturation was calculated and its anti-inflammatory properties were evaluated through Bovine Serum Albumin Assay and Egg Albumin Assay. Results: Quercetin mouthwash showed parallel anti-inflammatory properties and showed a proportionate increase in anti-inflammatory properties with the increase in the concentration of the mouthwash. Comparable inhibition of protein denaturation at 10µl and 50µl concentrations with a proportionate variation of 1 percent (p>0.05) to the control in Egg Albumin Assay and 47 percent and 83 percent denaturation at 10µl and 50µl of Bovine Serum Albumin Assay were observed. Conclusion: Quercetin mouthwash has shown significant anti-inflammatory activity and hence is considered a potent anti-inflammatory agent comparable to Diclofenac sodium. It is found to be a suitable agent as an oral formulation for reducing the progression of inflammatory conditions(AU)
Introducción: La periodontitis es una pandemia, ya que alrededor del 14 por ciento de las personas en todo el mundo padecen periodontitis grave. Una intervención precoz en la enfermedad podría, probablemente, reducir su progresión y eliminar la necesidad de extraer los dientes afectados. La quercetina es un candidato probable, ya que tiene propiedades antiinflamatorias ejemplares. Su presencia de grupos hidroxilos fenólicos contribuye en gran medida a sus actividades antioxidantes y antiinflamatorias. Objetivos: El estudio presenta la formulación del colutorio de quercetina y evalúa sus propiedades antiinflamatorias en comparación con el diclofenaco sódico. Métodos: Se preparó un colutorio de quercetina, utilizando un agente bioactivo obtenido comercialmente. Se utilizó como fármaco de referencia un antiinflamatorio no esteroideo estándar, el diclofenaco. Se calculó el porcentaje de inhibición de la desnaturalización de proteínas y se evaluaron sus propiedades antiinflamatorias mediante ensayo con albúmina de suero bovino y con albúmina de huevo. Resultados: El colutorio de quercetina mostró propiedades antiinflamatorias paralelas y mostró un aumento proporcional de las propiedades antiinflamatorias con el aumento de la concentración del colutorio. Se observó una inhibición comparable de la desnaturalización de proteínas a concentraciones de 10µl y 50µl con una variación proporcional del 1 por ciento (p > 0,05), respecto al control en el ensayo de albúmina de huevo y una desnaturalización del 47 por ciento y 83 por ciento a 10µl y 50µl del ensayo de albúmina de suero bovino. Conclusiones: El enjuague bucal de quercetina ha mostrado una actividad antiinflamatoria significativa, por lo que se considera un potente agente antiinflamatorio comparable al diclofenaco sódico. Se considera un agente adecuado como formulación oral para reducir la progresión de las afecciones inflamatorias(AU)
Subject(s)
Humans , Periodontitis/epidemiology , Quercetin/therapeutic use , Oral Health , Anti-Inflammatory Agents/therapeutic use , Mouthwashes/administration & dosageABSTRACT
SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.
El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.
Subject(s)
Animals , Rats , Quercetin/administration & dosage , Chemical and Drug Induced Liver Injury, Chronic/drug therapy , Resveratrol/administration & dosage , Acetaminophen/toxicity , Acute Disease , NF-kappa B/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Rats, Sprague-Dawley , Nitric Oxide Synthase/antagonists & inhibitors , Protective Agents , Drug Therapy, Combination , Drug OverdoseABSTRACT
ABSTRACT Introduction: Quercetin (Q) is a flavonoid that has been shown to be an antioxidant in vitro. A current review is necessary to evaluate whether Q can improve biochemical damage markers following exercise-induced muscle damage (EIMD) and delayed onset muscle soreness (DOMS). Objective: Specify the impact of Q supplementation on EIMD, DOMS, and inflammatory cytokines (IL-6, IL-10, and TNF-α) after exercise. Methods: Participants (n=28) were randomly assigned to Q (1000 mg/day) and placebo (PLA). Intake was done 48 hours before EMID to 96 hours after EMID (one week). Before EIMD (PRE) and 24, 48, 72, and 96 hours after EIMD, blood samples were collected for CK and measurement of inflammatory cytokines. ANOVA test was used for data analysis with a significance P > 0.05. Results: Peak DOMS was seen 48 hours after EIMD, regardless of the DOMS combination. Q had a significant reducing effect on CK response at 24 hours (-43%), 48 hours (-48%), 72 hours (-56%), and 96 hours (-67%) after EIMD compared to placebo. IL-10 and IL-6 did not change statistically for the applied sample size. TNF-α was lower by Q intake significantly at 24 hours (-24%), 48 hours (-22%), and 96 hours (-22%) compared to PLA. Furthermore, the TNF-α trend was lower with Q intake at 72 hours (-19%). Conclusion: Q supplementation decreased biological inflammation during post-IMD recovery but not quadriceps DOMS. Level of Evidence: Therapeutic Studies - Investigating Treatment Outcomes.
RESUMO Introdução: A quercetina (Q) é um flavonóide que provou ser um antioxidante in vitro. Fez-se necessária uma revisão atual projetada para avaliar se a Q pode melhorar os marcadores bioquímicos de dano após o dano muscular induzido pelo exercício (EIMD) e a dor muscular de início retardado (DOMS). Objetivo: O objetivo da revisão atual foi especificar o impacto da suplementação Q sobre EIMD, DOMS e citocinas inflamatórias (IL-6, IL-10 e TNF-α) após o exercício. Métodos: Os participantes (n=28) foram alocados em Q (1000 mg/dia) e placebo (PLA) aleatoriamente. Fez-se ingestão 48 horas antes da EMID a 96 horas após a EMID (uma semana). Antes da EIMD (PRE) e 24, 48, 72 e 96 horas após a EIMD, amostras de sangue coletadas para CK e medição de citocinas inflamatórias. O teste ANOVA foi usado para análise de dados com significância P > 0,05. Resultados: O pico DOMS foi visto em 48 horas após EIMD, independentemente da combinação de DOMS. Q teve um efeito de redução significativo na resposta CK em 24 horas (-43%), 48 horas (-48%), 72 horas (-56%) e 96 horas (-67%) após a EIMD em comparação com placebo. IL-10 e IL-6 não mudaram estatisticamente para o tamanho da amostra aplicada. TNF-α foi menor pela ingestão de Q significativamente às 24 horas (-24%), 48 horas (-22%), e 96 horas (-22%) em comparação com o PLA. Ademais, a tendência TNF-α foi menor com a ingestão de Q às 72 horas (-19%). Conclusão: A suplementação de Q diminuiu a inflamação biológica durante a recuperação pós EIMD, porém não os DOMS do quadríceps. Nível de evidência: Estudos Terapêuticos - Investigando os Resultados de tratamento.
RESUMEN Introducción: La quercetina (Q) es un flavonoide que ha demostrado ser un antioxidante in vitro. Por ello, es necesaria una revisión actual diseñada para evaluar si la Q puede mejorar los marcadores bioquímicos de daño tras el daño muscular inducido por el ejercicio (EIMD) y el dolor muscular de aparición retardada (DOMS). Objetivo: El objetivo de la presente revisión fue especificar el impacto de la suplementación con Q en el EIMD, el DOMS y las citoquinas inflamatorias (IL-6, IL-10 y TNF-α) después del ejercicio. Métodos: Los participantes (n=28) fueron asignados aleatoriamente a Q (1000 mg/día) y a placebo (PLA). La ingesta se realizó desde 48 horas antes de la EMID hasta 96 horas después de la misma (una semana). Antes de la EMID (PRE) y 24, 48, 72 y 96 horas después de la EMID, se tomaron muestras de sangre para la CK y la medición de citoquinas inflamatorias. Se utilizó la prueba ANOVA para el análisis de los datos con una significancia P > 0,05. Resultados: El pico de DOMS se observó en las 48 horas posteriores a la EIMD, independientemente de la combinación de DOMS. Q tuvo un efecto significativamente reductor en la respuesta de la CK a las 24 horas (-43%), 48 horas (-48%), 72 horas (-56%) y 96 horas (-67%) después de la EIMD en comparación con el placebo. La IL-10 y la IL-6 no cambiaron estadísticamente para el tamaño de muestra aplicado. El TNF-α se redujo significativamente con la ingesta de Q a las 24 horas (-24%), a las 48 horas (-22%) y a las 96 horas (-22%) en comparación con el PLA. Además, la tendencia del TNF-α fue menor con la ingesta de Q a las 72 horas (-19%). Conclusión: La suplementación con Q disminuyó la inflamación biológica durante la recuperación después de un IMD, pero no el DOMS del cuádriceps. Nivel de evidencia: Estudios terapéuticos -Investigación de los resultados del tratamiento.
ABSTRACT
UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.
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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.
Subject(s)
Humans , Colorectal Neoplasms/drug therapy , Catechin/analogs & derivatives , Catechin/pharmacology , Quercetin/pharmacology , Cell Cycle , Annexin A5 , Cell Line, Tumor , Cell ProliferationABSTRACT
OBJECTIVE@#To explore the mechanism underlying the inhibitory effect of quercetin against testicular oxidative damage induced by a mixture of 3 commonly used phthalates (MPEs) in rats.@*METHODS@#Forty male Sprague-Dawley rats were randomly divided into control group, MPEs exposure group, and MPEs with low-, median- and high-dose quercetin treatment groups. For MPEs exposure, the rats were subjected to intragastric administration of MPEs at the daily dose of 900 mg/kg for 30 consecutive days; Quercetin treatments were administered in the same manner at the daily dose of 10, 30, and 90 mg/kg. After the treatments, serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testicular malondialdeyhde (MDA), catalase (CAT) and superoxide dismutase (SOD) were detected, and testicular pathologies of the rats were observed with HE staining. The expressions of nuclear factor-E2-related factor 2 (Nrf2), Kelch-like ECH2 associated protein 1 (Keap1) and heme oxygenase 1 (HO-1) in the testis were detected using immunofluorescence assay and Western blotting.@*RESULTS@#Compared with the control group, the rats with MPEs exposure showed significant reductions of the anogenital distance, weight of the testis and epididymis, and the coefficients of the testis and epididymis with lowered serum testosterone, LH and FSH levels (P < 0.05). Testicular histological examination revealed atrophy of the seminiferous tubules, spermatogenic arrest, and hyperplasia of the Leydig cells in MPEs-exposed rats. MPEs exposure also caused significant increments of testicular Nrf2, MDA, SOD, CAT and HO-1 expressions and lowered testicular Keap1 expression (P < 0.05). Treatment with quercetin at the median and high doses significantly ameliorated the pathological changes induced by MPEs exposure (P < 0.05).@*CONCLUSION@#Quercetin treatment inhibits MPEs-induced oxidative testicular damage in rats possibly by direct scavenging of free radicals to lower testicular oxidative stress and restore the regulation of the Nrf2 signaling pathway.
Subject(s)
Rats , Male , Animals , Testis , Quercetin/pharmacology , Rats, Sprague-Dawley , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Oxidative Stress , Testosterone/pharmacology , Superoxide Dismutase/metabolism , Follicle Stimulating Hormone , Luteinizing HormoneABSTRACT
OBJECTIVE@#To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS).@*METHODS@#Fourteen apolipoprotein E-deficient (ApoE-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot.@*RESULTS@#Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05).@*CONCLUSION@#Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.
Subject(s)
Mice , Animals , Apelin , Tissue Plasminogen Activator/metabolism , Quercetin/therapeutic use , AMP-Activated Protein Kinases/metabolism , Sirtuin 1/metabolism , Signal Transduction/physiology , Atherosclerosis/metabolism , Apolipoproteins EABSTRACT
Objective:To investigate potential effective components of traditional Chinese medicine and their molecular mechanisms of action in the anti-angiogenic treatment of Kaposi′s sarcoma based on network pharmacology, and to predict key targets and signal pathways in the anti-angiogenic treatment of Kaposi′s sarcoma with traditional Chinese medicine.Methods:According to the previous network pharmacology-based analysis results, main chemical components and targets of Rhizoma Polygoni Cuspidati, Cortex Mori, Rhizoma Smilacis Glabrae and Fructus Perillae were obtained by using the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP); potential therapeutic targets for angiogenesis and Kaposi′s sarcoma were obtained by searching the GeneCard, OMIM, DrugBank and TTD databases, and a Venn diagram was constructed to obtain targets for the interaction between Kaposi′s sarcoma and anti-angiogenic drug components; a protein-protein interaction model was constructed using the STRING 11.5 platform; the Cytoscape 3.6.0 software was used to construct the component-target visual network. Meanwhile, the Metascape platform was used to analyze the Gene Ontology (GO) functions and the enrichment of Kyoto Encyclopedia of Genes and Genome (KEGG) -based pathways. The main active ingredients and core targets obtained through the above analyses were then verified by molecular docking. Results:The core components of anti-Kaposi′s sarcoma angiogenesis drugs were resveratrol (degree: 142), quercetin (degree: 141), kaempferol (degree: 56), luteolin (degree: 56), β-sitosterol (degree: 37), arachidonic acid (degree: 36), naringenin (degree: 36), etc., and the core target was prostaglandin-endoperoxide synthase 2 (PTGS2). KEGG analysis revealed that the cancer signaling pathways were the important pathways related to the inhibiton of angiogenesis in Kaposi′s sarcoma; functional enrichment analysis showed that the positive regulation of cell migration was the most significantly enriched GO term in the biological process category. Molecular docking results showed that resveratrol, quercetin, kaempferol and luteolin had good affinity with PTGS2, especially quercetin and luteolin exhibited the strongest binding abilities to PTGS2, with the binding energies being -9.4 and -9.5 kcal/mol, respectively.Conclusion:This study showed that the 4 traditional Chinese medicines recorded in TCMSP (including Rhizoma Polygoni Cuspidati., Cortex Mori, Rhizoma Smilacis Glabrae and Fructus Perillae) may play an anti-angiogenic role by regulating cancer signaling pathways and acting on targets such as PTGS2, and predicted the possible anti-angiogenesis mechanisms of traditional Chinese medicines in Kaposi′s sarcoma.
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OBJECTIVE The abnormal amyloid-β(Aβ)and oxidative stress assiociated with the progression of Alzheimer disease(AD).Quercetin has been reported to possess antioxidant and anti-inflammatory properties in neurodegenerative disorders.In this present study,we designed to characterize the mechanisms by which quer-cetin exerts neuroprotective effects in murine neuroblas-toma N2a cells stably expressing human Swedish mutant amyloid precursor protein(N2a/APP).METHODS N2a/APP cells were treated with quercetin at concentrations of 10,20 and 50 μ mol·L-1 for 24 h.Cell viability was examined with CCK-8 assays.The protein levels of ERK1/2 and Akt were detected by Western blotting.Intra-cellular reactive oxygen species(ROS)was detected by a fluorescent probe 2,7-dichlorofluorescein diacetate(DCFH-DA).The mitochondrial membrane potential(Δψ m)in N2a/APP cells was detected by using JC-1 staining method.Immunofluorescence was used to detect the generation of 8-hydroxy-2′-deoxyguanosine(8-OHdG)and 4-hydroxynonenal(4-HNE).RESULTS Quercetin attenuated the enhancement of p-ERK1/2,reductions of p-Akt,and decreased levels of APP expression.More-over,quercetin alleviated loss of mitochondria membrane potential(MMP)since it attenuates these oxidative stress,as reflected in the levels of ROS,4-HNE and 8-OHdG,was elevated in N2a/APP cells and these effects were again ameliorated by quercetin.CONCLUSION Neuroprotection by quercetin in N2a/APP cells involves normalizing the impaired mitochondrial function and reducing oxidative stress via inactivation of the ERK1/2 and activation of the Akt pathways.
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Objective:To determine the contents of quercetin, kaempferol, total flavonoids and extracts in 52 samples of Lysimachiae Herba collected from different origins; To analyze the quality differences of Lysimachiae Herba among different producing areas. Methods:The quercetin and kaempferol contents of the Lysimachiae Herba from Guizhou Province, Sichuan Province and Chongqing were determined by HPLC, and the total flavonoids were determined by Symergy HTX microplate reader. Results:The total content of quercetin and kaempferol in 52 samples was among 0.146 2-2.517 0 mg/g, with an average content of 0.872 6 mg/g, among which the average content of Sichuan was 1.073 2 mg/g, that of Guizhou was 0.705 4 mg/g, and that of Chongqing was 0.865 1 mg/g. Among them, 20 samples reached the standard of the Chinese Pharmacopoeia. The average content of the samples that met the standard was 1.439 7 mg/g. The compliance rate of samples collected in Guizhou, Sichuan and Chongqing reached 12.5%, 62.5%, and 38.8% respectively. The total flavonoid content of 52 samples was among 0.994 2- 3.866 4 mg/g, and 52 samples were in conformity with the ethanol hot extract standard of the Chinese Pharmacopoeia. Conclusions:The total contents of quercetin and kaempferol from different sources in Sichuan, Guizhou and Chongqing are quite different, and the total contents of quercetin and kaempferol collected from the same district and county are also quite different, and the compliance rate is low. There are great differences in total flavonoids in different producing areas and different populations of Lysimachiae Herba samples collected in the field.
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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.
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.
Subject(s)
Humans , /therapeutic use , Apoptosis/drug effects , Catechin/administration & dosage , Colorectal Neoplasms/drug therapy , Quercetin/administration & dosageABSTRACT
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.
ABSTRACT
AIM: To investigate the function and mechanism of quercetin (Que) in anti-fibrosis in vitro and in vivo from the perspective of interfering with the glycolysis of renal interstitial fibroblasts. METHODS: ln vivo experiments, mice were administered in groups, kidneys were dissected, weighed and examined histopathologically and biochemically; ln vitro experiments, rat normal renal fibroblasts (NRK-49F cells) were treated with different reagents, proteins were extracted, and NRK-49F cell activation indicators such as α-smooth muscle actin (α-SMA) were detected by protein immunoblotting (Western Blot). The expression of the proteins, such as proliferating cell nuclear antigen (PCNA), was examined by protein immunoblotting (Western Blot), and the effect of Que on glucose uptake in NRK-49F cells induced by transforming growth factor-β (TGF-β1) and epidermal growth factor (EGF) was examined by fluorescence assay; the lactate content of cells in different experimental groups was examined by lactate assay kit; the effect of Que on glucose uptake in NRK-49F cells induced by TGF-β1 and EGF was examined by fluorescence quantitative PCR. EGF-induced mRNA of hexokinase (HK2), phosphofruc-tokinase 1 (PFK1) and muscle pyruvate kinase isozyme 2 (PKM2), key enzymes of glycolysis in NRK-49F cells. RESULTS: Compared with the UUO group, the morphological structures of kidney tissues in the Que administration group were all alleviated to different degrees, which were related to the inhibition of glycolysis, and the serum levels of urea nitrogen (BUN) and blood creatinine (Scr) in mice showed a significant downward trend; lactate production and glucose uptake in NRK-49F cells were gradually reduced, and Que affected TGF-β1 and EGF-induced RIF of mRNA levels of key enzymes of glycolysis gradually decreased and were associated with PKM2. CONCLUSION: Que inhibits PKM2 enzyme activity and glycolysis in NRK-49F cells and reduces TGF-β1-induced myofibroblast activation.