A ternary early-strengthening agent consisting of calcium formate+triethanolamine+lithium sulfate was compounded with quercetin to shorten the setting time of cementitious materials while ensuring their early strength...A ternary early-strengthening agent consisting of calcium formate+triethanolamine+lithium sulfate was compounded with quercetin to shorten the setting time of cementitious materials while ensuring their early strength.The optimum ratio of the three early-strengthening agents was determined as 0.5%calcium formate+0.04%triethanolamine+0.4%lithium sulfate by response surface methodology.The effects of the ternary early-strengthening agent composed of calcium formate+triethanolamine(TEA)+lithium sulfate on cementitious pore sealing materials under the synergistic effect of quercetin were studied by means of the performance tests of compressive strength,fluidity,and setting time,and the microstructural characterizations of X-ray powder diffractometer(XRD),thermogravimetry(TG-DSC)and scanning electron microscopy(SEM).The study shows that the synergistic effect of ternary early-strengthening agent and quercetin forms a multi-performance composite admixture for cementitious materials.The best performance was obtained with the compounding scheme of 0.5%calcium formate+0.04%triethanolamine+0.4%lithium sulfate ternary early-strengthening agent and 0.05%quercetin.The compressive strength of 1,3,7,and 28 d are 94.8%,39.8%,42%,and 28%higher than those of the blank group,respectively.The initial time and final setting time are 41 and 57 minutes,respectively.According to the microscopic analysis,the network and fibrous C-S-H gels generated by ternary early-strengthening agents are attached to the surface promoted by quercetin,which forms skeleton support while thickening and solidifying the cement slurry,which enhances the early compressive strength of the cement-based materials.展开更多
Hyperuricemia is a prevalent metabolic disorder resulting from dysregulation of purine metabolism,often accompanied by inflammation.It is characterized by an abnormal elevation in uric acid(UA)levels.In our investigat...Hyperuricemia is a prevalent metabolic disorder resulting from dysregulation of purine metabolism,often accompanied by inflammation.It is characterized by an abnormal elevation in uric acid(UA)levels.In our investigation,the combined treatment with Lactiplantibacillus plantarum DY1 and quercetin suppressed the activity of xanthine oxidase and adenosine deaminase,decreased the levels of UA,tumor necrosis factor alpha(TNF-α)and interleukin 1β(IL-β),downregulated gene expression of urate transporter 1(URAT1)and glucose transporter 9(GLUT9),and upregulated organic anion transporter 1(OAT1)and ATP-binding cassette transporter subfamily G member 2(ABCG2).The combination increased the abundance of Lactobacillus and decreased the abundance of norank_f_norank_o__Clostridia_UCG-014 and Roseburia.Metabolomics analysis revealed that the combination of probiotics and quercetin exhibited distinct metabolic pathways compared to their individual administrations.When compared to probiotics alone,the combination led to alterations in glutathione metabolism(oxidized glutathione and glutathione)as well as sphingolipid metabolism(sphingosine and sphinganine).When compared to quercetin alone,the combination resulted in variations in tryptophan metabolism(indole-3-acetamide,5-hydroxy-L-tryptophan,indoleacetaldehyde,3-(3-indolyl)-2-oxopropanoic acid,3-indoleacetic acid and 3-methylindole)along with purine metabolism(UA,xanthosine,cyclic adenosine monophosphate(cAMP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)).The subsequent fecal microbiota transplantation proved that the effect of the combination on reducing UA levels was mediated by the gut microbiota.Therefore,this new combination can be considered a promising adjuvant therapy capable of synergistically alleviating hyperuricemia.展开更多
The purpose of this experiment was to investigate the effect and mechanism of quercetin on reproductive performance in perinatal sows.According to the similar principle of parity and body weight,24 perinatal sows were...The purpose of this experiment was to investigate the effect and mechanism of quercetin on reproductive performance in perinatal sows.According to the similar principle of parity and body weight,24 perinatal sows were randomly divided into four treatments with six replicates,including normal control and three treatments fed by a basal diet supplemented with 0,0.025%,0.050%,and 0.075%quercetin,respectively.The feeding trial was conducted from 100 days of gestation to 28 days post-partum.Reproductive performance,colostrum composition,serum indexes of antioxidation,inflammation,hormones,and the diversity and relative abundance of fecal microflora were determined in perinatal sows.Compared with the control,quercetin significantly reduced the rate of constipation,serum content of malondialdehyde(MDA),prolactin(PRL),and progesterone(PROG),and significantly increased the content of serum estradiol(E2)and insulin-like growth factor-1(IGF-1)in colostrum of perinatal sows(P<0.05).Meanwhile,0.025%quercetin significantly increased glutathione(GSH)content in serum(P<0.05),0.050%quercetin significantly reduced the rate of backfat loss(P<0.05),and 0.075%quercetin significantly increased immunoglobulin M(IgM)content in colostrum of perinatal sows(P<0.05).In addition,0.050%and 0.075%quercetin significantly shortened estrus interval(P<0.05)and significantly increased the content of IgA and IgG in colostrum(P<0.05)and dopamine(DA)content in serum of perinatal sows(P<0.05).Quercetin significantly decreased the content of nitric oxide(NO),IL-1β,IL-6,TNF-α,and MCP-1 in serum(P<0.05)and significantly improved microflora abundance and diversity in feces of perinatal sows(P<0.05).In conclusion,dietary supplementation of quercetin reduced oxidative stress and inflammatory responses and regulated intestinal microflora in perinatal sows,thus improved reproductive performance in perinatal sows.Under this experimental condition,the optimal supplementation with dietary quercetin was 0.075%in perinatal sows.展开更多
Background Granulosa cell(GC)apoptosis,ferroptosis,and other programmed cell death processes are markers of follicular aging.Quercetin has been shown to reduce ferroptosis,however,its effects on ferroptosis in poultry...Background Granulosa cell(GC)apoptosis,ferroptosis,and other programmed cell death processes are markers of follicular aging.Quercetin has been shown to reduce ferroptosis,however,its effects on ferroptosis in poultry remains unexplored.Our preliminary study identified ferroptosis in aging ovaries.Therefore,in the present study,540-day-old Mountain Plum-blossom chickens were fed with quercetin supplementation at varying doses(0.2,0.4,and 0.6 g/kg),and examined its molecular effects on GC ferroptosis using an in vitro Erastin-induced model.Results The results showed that quercetin supplementation significantly increased egg production,which confirmed its potential to alleviate ferroptosis in chicken ovarian tissue.The in vitro experiment revealed that quercetin and Fer-1(positive control)mitigated Erastin-induced ferroptosis in GCs.Further,transcriptome analysis revealed that querce-tin modulated key genes such as acyl-CoA synthetase long-chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11),and transferrin receptor(TFRC),involved in ferroptosis regulation.The results further showed that quercetin also reduced Erastin-induced apoptosis and inflammation by modulating the expression of genes and proteins related to apoptosis and inflammatory factors(NF-κB,TNF-α,IL-6,and IL-10).Conclusion Taken together,the results showed that quercetin improves egg production performance in chickens and mitigates ovarian ferroptosis in aging hens,and inhibits Erastin-induced ferroptosis,inflammation,and apoptosis in GCs.These findings revealed the protective role of quercetin in poultry ovarian tissue and its cellular mechanisms against detrimental factors in poultry production.展开更多
Background:Neurodegenerative diseases(NDs),including Alzheimer‘s disease,Parkinson‘s disease,and Huntington‘s disease,are complex and challenging due to their intricate pathophysiology and limited treatment options...Background:Neurodegenerative diseases(NDs),including Alzheimer‘s disease,Parkinson‘s disease,and Huntington‘s disease,are complex and challenging due to their intricate pathophysiology and limited treatment options.Methods:This review systematically sourced articles related to neurodegenerative diseases,neurodegeneration,quercetin,and clinical studies from primary medical databases,including Scopus,PubMed,and Web of Science.Results:Recent studies have included quercetin to impact the cellular and molecular pathways involved in neurodegeneration.Quercetin,a flavonoid abundant in vegetables and fruits,is gaining attention for its antioxidant,anti-inflammatory,and antiapoptotic properties.It regulates signaling pathways such as nuclear factor-κB(NF-κB),sirtuins,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt).These pathways are essential for cellular survival,inflammation regulation,and apoptosis.Preclinical and clinical studies have shown that quercetin improves symptoms and pathology in neurodegenerative models,indicating promising outcomes.Conclusions:The study explores the potential of incorporating laboratory research into practical medical treatment,focusing on quercetin‘s neuroprotective effects on NDs and its optimal dosage.展开更多
Objective:Limb ischemia-reperfusion injury(LIRI)may lead to tissue necrosis and loss of function,even life-threatening.Our previous study found that Tao-Hong-Si-Wu decoction(THSWD)had some efficacy in treating of LIRI...Objective:Limb ischemia-reperfusion injury(LIRI)may lead to tissue necrosis and loss of function,even life-threatening.Our previous study found that Tao-Hong-Si-Wu decoction(THSWD)had some efficacy in treating of LIRI.Quercetin,the major component of THSWD,was selected further to uncover the molecular mechanism underlying its treatment of LIRI.Methods:In this study,myoblasts were isolated fromrat gastrocnemiusmuscle tissue,and an in vitro LIRI model was established.The cell counting kit-8(CCK-8)and colony formation assay were used to evaluate the impact of quercetin on LIRI-induced myoblast viability and proliferation.Lactate dehydrogenase(LDH)activity wasmeasured to detectmyoblast injury in the LIRI model.Theapoptosis ofmyoblasts was evaluated byHoechst staining and flow cytometry.In addition,molecular docking analysis was performed to predict the interaction between quercetin and NADPH oxidase 2(NOX-2).Subsequently,we investigated the molecular mechanism of quercetin in LIRI-induced myoblasts by overexpressing NOX-2.Results:The myogenic marker Desmin was highly expressed in isolatedmyoblasts.In the LIRImodel,myoblast viability and proliferation were decreased,and cell injury and apoptosis levels were increased.In addition,NOX-2 was highly expressed in the LIRI model.At the same time,LIRI induction promoted the up-regulation of oxidative stress and inflammatory response.Quercetin significantly reversed the effects of LIRI treatment on myoblasts in a concentration-dependent manner.Molecular docking suggested an interaction between quercetin and NOX-2.Further overexpression of NOX-2 inhibited the effect of quercetin on LIRI-induced myoblasts.Conclusion:Quercetin could reduce inflammatory response and oxidative stress by inhibiting NOX-2,thus playing a therapeutic role in treating LIRI.展开更多
BACKGROUND Schizophrenia is a complex psychiatric disorder with significant functional impairment.Although olanzapine is effective in treating positive symptoms,its efficacy against negative symptoms and cognitive def...BACKGROUND Schizophrenia is a complex psychiatric disorder with significant functional impairment.Although olanzapine is effective in treating positive symptoms,its efficacy against negative symptoms and cognitive deficits is limited.Yueju pill,a traditional Chinese herbal formula,has shown potential in improving these domains,but its mechanisms remain largely unexplored.AIM To evaluate the therapeutic efficacy and underlying mechanisms of Yueju pill combined with olanzapine in treating schizophrenia.METHODS Ninety-seven patients with schizophrenia were randomly assigned to an intervention group(n=48)receiving olanzapine and Yueju pill,or a control group(n=49)receiving olanzapine and a placebo for 8 weeks.Symptom severity was assessed using the positive and negative syndrome scale,the scale for the assessment of negative symptoms,and cognitive and social function scales.Serum levels of brain-derived neurotrophic factor(BDNF),dopamine(DA),and serotonin(5-HT)were measured.Network pharmacology analysis identified key chemical components and target genes involved in the treatment response.RESULTS The intervention group demonstrated a significantly higher overall efficacy rate(93.75%)compared to the control group(73.47%,P<0.05).Improvements in psychiatric symptoms,cognitive function,and social performance were more pronounced in the intervention group.Additionally,serum levels of BDNF,DA,and 5-HT were significantly higher in the intervention group(P<0.05).Network pharmacology analysis revealed quercetin as a key component,modulating genes such as CHRM1,GSK3B,and KCNH2,crucial in DA signaling.CONCLUSION Yueju pill,when combined with olanzapine,significantly improves clinical outcomes in schizophrenia patients,with safety comparable to olanzapine alone.展开更多
Background:Breast cancer ranks as the most common cancer in women globally,presenting major challenges primarily due to the emergence of resistance to existing therapies and the adverse side effects linked with these ...Background:Breast cancer ranks as the most common cancer in women globally,presenting major challenges primarily due to the emergence of resistance to existing therapies and the adverse side effects linked with these treatments.Natural compounds,such as quercetin,a flavonoid found in Artemisia annua,have gained attention for their multi-targeted therapeutic potential.This research aims to investigate the pharmacological effects of quercetin in inducing cellular senescence in breast cancer cells utilizing network pharmacology.Methods:Initially,the active compounds of Artemisia annua were identified through the Traditional Chinese Medicine Systems Pharmacology database.The breast cancer-related genes were gathered from various databases.The intersection between the genes associated with breast cancer and the targets of active pharmaceutical ingredients was analyzed.Additionally,the regulatory network of active ingredients and their targets was researched.Further,protein-protein interaction was acquired from STRING database and core targets were analyzed.The analyses of Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were conducted utilizing R programming language.Results:In Artemisia annua,18 active compounds were identified along with their associated target proteins,among which quercetin exhibiting the highest number of target proteins.2897 disease-related genes were discovered,and 145 drug-disease intersection targets were selected.The analysis focused on the impact of quercetin on cellular senescence,informed by core target analysis and enrichment results.Molecular docking studies demonstrated the stable binding of quercetin to cyclin-dependent kinase 2(CDK2),which was chosen for experimental validation.Conclusion:The research highlights the promising therapeutic efficacy of quercetin on breast cancer by the induction of cellular senescence,offering valuable biological insights and establishing a foundation for future research.展开更多
Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized ...Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized inhalation,exploring its underlying mechanisms.Methods:The anti-fibrotic properties of nebulized YQHTSJ were assessed using a bleomycin(BLM)-induced PF mouse model.RNA sequencing identified differentially expressed genes(DEGs),and subsequent gene enrichment analysis,along with transcription factor(TF)prediction,revealed YQHTSJ-regulated DEGs.Active components and targets of YQHTSJ were retrieved from the HERB database,leading to the identification of key TFs interacting with DEGs.Quercetin,a constituent of YQHTSJ,was evaluated for its effects on transforming growth factor-β1-induced myofibroblast activation and BLM-induced PF.The direct binding interaction between quercetin and the key TF Jun proto-oncogene(JUN)was confirmed through molecular docking studies and the cellular thermal shift assay(CETSA)experiments.Results:Nebulized YQHTSJ was found to significantly inhibit PF and inflammation in the mouse model.RNA sequencing identified 135 DEGs regulated by YQHTSJ,and 27 key TFs associated with these DEGs were predicted.Among YQHTSJ’s potential targets,41 were identified as TFs,with six-JUN,Fos proto-oncogene,MYC proto-oncogene,RELA proto-oncogene,nuclear factor kappa B subunit 1,and peroxisome proliferator activated receptor alpha-recognized as key TFs targeted by YQHTSJ.Molecular docking and CETSA experiments confirmed that quercetin directly targets JUN protein and inhibits its phosphorylation,thereby contributing to the suppression of myofibroblast activation and PF.Conclusion:The potential mechanisms of YQHTSJ and its component quercetin in combating PF may involve the regulation of critical TFs like JUN and the suppression of pathogenic gene expression.展开更多
[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treate...[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treated with quercetin.[Results]Statistical analysis showed that 1264 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 716 were significantly up-regulated and 548 were significantly down-regulated;191 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 129 were significantly up-regulated and 62 were significantly down-regulated.By comparing the expression differences of these mRNAs and miRNAs in different samples,six different expression patterns were clustered.The expression of the above miRNAs was verified by real-time quantitative PCR(qPCR),and the results were highly consistent with the transcriptome sequencing data.In addition,Gene Ontology annotation and functional enrichment analysis of miRNA target genes showed that CTGF,VHL and H19,which are related to the regulation of cell proliferation signal transduction,were predicted to be new targets of differential miRNAs such as miR494-3p and miR675-3p and may play an important regulatory role in the process of Quercetin inhibiting the proliferation of Sune-1 cells.[Conclusions]This study provides a basis for the rational use of anti-tumor functional components of traditional Chinese medicine,and also provides a theoretical basis for the targeted therapy of nasopharyngeal carcinoma.展开更多
Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this stud...Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this study:three groups were given streptozotocin to induce diabetes,and one group was given a normal control.For treatment groups,each group received either metformin(200 mg/kg body weight)or quercetin(50 mg/kg body weight)for a month.The expression of SREBP1c was detected by quantitative RT-PCR and fibrosis-related proteins(TGF-βand p-Smad3)was evaluated by Western blot.Furthermore,MCP and IL-1βwere determined by ELISA.Results:Quercetin significantly reduced insulin and glucose levels.Besides,it reduced the serum levels of ALT,AST,and ALP,improved lipid profile,lowered the MDA level,increased SOD activity,decreased the rise in MCP-1 and IL-1β,inhibited the TGF-β/Smad3 signaling pathway,decreasedα-SMA and SREBP1c expression,and increased AMPK(P<0.05).Conclusions:Quercetin could significantly mitigate hepatic damage by modulating the expression of pro-inflammatory cytokines and fibrosis markers.展开更多
Quercetin is a natural compound with potent antiviral effects;however,its role in the treatment of herpes simplex keratitis(HSK)remains underexplored.Here,we investigated the antiviral effects of quercetin against her...Quercetin is a natural compound with potent antiviral effects;however,its role in the treatment of herpes simplex keratitis(HSK)remains underexplored.Here,we investigated the antiviral effects of quercetin against herpes simplex virus 1(HSV-1).By examining different phases of viral infection in human corneal epithelial cells(HCECs),we found that 30μmol/L quercetin inhibits HSV-1 replication primarily by disrupting viral attachment.RNA-sequencing and subsequent analyses revealed that the nuclear factor E2-related factor 2(Nrf2)was upregulated by quercetin in a dose-dependent manner.Knocking down Nrf2 partially compromised quercetin's antiviral effect.Importantly,topical application of 100μmol/L quercetin alleviated HSK severity in mice,reduced viral titers in tears,and inhibited VP16 expression in the cornea and trigeminal ganglia.These findings demonstrate the antiviral effect of quercetin against HSV-1 and provide a foundation for mechanistic studies to elucidate its therapeutic potential in HSK.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a chronic,progressive inflammatory condition of the intestine.Mesenchymal stem cell(MSC)therapy for IBD has made significant progress in recent years.To better exploit the ...BACKGROUND Inflammatory bowel disease(IBD)is a chronic,progressive inflammatory condition of the intestine.Mesenchymal stem cell(MSC)therapy for IBD has made significant progress in recent years.To better exploit the therapeutic potential of MSCs,pretreatment strategies are employed to enhance their therapeutic capabilities.As a compound with diverse pharmacological effects,quercetin(QUR)is applied to pretreat human umbilical cord-derived MSCs(hUCMSCs)in this study,thereby augmenting their immunotherapeutic potential.AIM To evaluate the therapeutic efficacy of QUR-pretreated hUCMSCs.METHODS We induced colitis in a mouse model using a 2,4,6-trinitrobenzenesulfonic acid solution.Intraperitoneal injection of QUR-pretreated hUCMSCs significantly improved clinical and pathological manifestations of colitis compared to the model group.Interestingly,the therapeutic effect was superior to that of untreated hUCMSCs.Mice exhibited significantly reduced weight loss,diminished infiltration of inflammatory cells observed in hematoxylin and eosin staining,improved Disease Activity Index and Histological Activity Index scores.Furthermore,colonic tissue analysis revealed a significant upregulation of the anti-inflammatory cytokine interleukin 10(IL-10),accompanied by a downregulation of the pro-inflammatory cytokine IL-6.Further tests also suggested that QUR pretreatment led to inhibition of Janus kinase/signal transducer and activator of transcription(STAT)phosphorylation.RESULTS Our study demonstrated that QUR pretreatment of hUCMSCs significantly enhanced their immune-regulatory capacity.This approach effectively mitigated colonic inflammation in a mouse colitis model by modulating the IL-10/Janus kinase/STAT signaling pathway.CONCLUSION These findings suggest that QUR pretreatment acts synergistically to augment the inherent anti-inflammatory and immune-regulatory properties of hUCMSCs,resulting in enhanced therapeutic efficacy for IBD treatment.展开更多
BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,...BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.展开更多
This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology a...This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology and experimental validation techniques.Active constituents of Astragali Radix and their corresponding targets were identified using the TCMSP database,while therapeutic targets associated with hypoxia-induced pulmonary hypertension were sourced from the GeneCards database.The Venn online tool facilitated the identification of overlapping targets between the active constituents of Astragali Radix and hypoxia-induced pulmonary hypertension.Interaction network diagrams depicting the relationship between Astragali Radix’s active constituents and their targets were constructed using Cytoscape software,with core targets and sub-networks identified using the CytoHubba plug-in.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted using the DAVID database.Additionally,the FerrDb database was consulted to analyze genes implicated in regulating ferroptosis.The investigation revealed 18 active constituents selected from Astragali Radix,with quercetin emerging as the key component.A total of 35 potential targets associated with Astragali Radix in regulating ferroptosis and addressing hypoxia-induced pulmonary hypertension were predicted.Experimental validation demonstrated that quercetin could inhibit the MAPK signaling pathway,resulting in reduced Fe2+and lipid peroxide levels,increased GPX4 expression,and the reversal of ferroptosis.In summary,this study elucidated the fundamental constituents and pivotal signaling pathways through which Astragali Radix modulated ferroptosis and mitigated hypoxia-induced pulmonary hypertension.Specifically,quercetin,a core constituent of Astragali Radix,was observed to inhibit ferroptosis in pulmonary arterial smooth muscle cells via the MAPK pathway and alleviate hypoxia-induced pulmonary hypertension.展开更多
Salt stress is a typical abiotic stress in plants that causes slow growth,stunting,and reduced yield and fruit quality.Fertilization is necessary to ensure proper crop growth.However,the effect of fertilization on sal...Salt stress is a typical abiotic stress in plants that causes slow growth,stunting,and reduced yield and fruit quality.Fertilization is necessary to ensure proper crop growth.However,the effect of fertilization on salt tolerance in grapevine is unclear.In this study,we investigated the effect of nitrogen fertilizer(0.01 and 0.1 mol L^(-1)NH_(4)NO_(3))application on the salt(200 mmol L^(-1)NaCl)tolerance of grapevine based on physiological indices,and transcriptomic and metabolomic analyses.The results revealed that 0.01 mol L^(-1)NH_(4)NO_(3) supplementation significantly reduced the accumulation of superoxide anion(O_(2)^(-)·),enhanced the activities of superoxide dismutase(SOD)and peroxidase(POD),and improved the levels of ascorbic acid(AsA)and glutathione(GSH)in grape leaves compared to salt treatment alone.Specifically,joint transcriptome and metabolome analyses showed that the differentially expressed genes(DEGs)and differentially accumulated metabolites(DAMs)were significantly enriched in the flavonoid biosynthesis pathway(ko00941)and the flavone and flavonol biosynthesis pathway(ko00944).In particular,the relative content of quercetin(C00389)was markedly regulated by salt and nitrogen.Further analysis revealed that exogenous foliar application of quercetin improved the SOD and POD activities,increased the AsA and GSH contents,and reduced the H_(2)O_(2) and O_(2)^(-)·contents.Meanwhile,10 hub DEGs,which had high Pearson correlations(R^(2)>0.9)with quercetin,were repressed by nitrogen.In conclusion,all the results indicated that moderate nitrogen and quercetin application under salt stress enhanced the antioxidant system defense response,thus providing a new perspective for improving salt tolerance in grapes.展开更多
Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is cl...Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applications of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.展开更多
Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five differ...Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five different stages of R. roxburghii fruit development. Flavonoids and the genes related to their biosynthesis were found to undergo significant changes in abundance across different developmental stages, and numerous quercetin derivatives were identified. We found three gene expression modules that were significantly associated with the abundances of the different flavonoids in R. roxburghii and identified three structural UDP-glycosyltransferase genes directly involved in the synthesis of quercetin derivatives within these modules. In addition, we found that RrBEH4, RrLBD1 and RrPIF8could significantly increase the expression of downstream quercetin derivative biosynthesis genes. Taken together,these results provide new insights into the metabolism of flavonoids and the accumulation of quercetin derivatives in R. roxburghii.展开更多
Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pat...Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.展开更多
Quercetin compounds have antioxidant,anti-inflammatory and anticancer pharmacological functions.Longterm exposure to acrylamide(AA)can cause liver injury and endanger human health.However,whether quercetin compounds c...Quercetin compounds have antioxidant,anti-inflammatory and anticancer pharmacological functions.Longterm exposure to acrylamide(AA)can cause liver injury and endanger human health.However,whether quercetin compounds can attenuate AA-induced liver injury and the specific mechanism are not clear.Here,we studied the mechanism and structure-activity relationship of quercetin compounds in reducing AA-induced hepatotoxicity in vivo and in vitro.In vivo studies found that quercetin-like compounds protect against AAinduced liver injury by reducing oxidative stress levels,activating the Akt/m TOR signaling pathway to attenuate autophagy,and improving mitochondrial apoptosis and endoplasmic reticulum stress-mediated apoptosis.In vitro studies found that quercetin compounds protected Hep G2 cells from AA by attenuating the activation of AA-induced autophagy,lowering reactive oxygen species(ROS)levels by exerting antioxidant effects and thus attenuating oxidative stress,increasing mitochondrial membrane potential(MMP),and improving apoptosis-related proteins,thus attenuating AA-induced apoptosis.Furthermore,the conformational differences between quercetin compounds correlated with their protective capacity against AA-induced hepatotoxicity,with quercetin showing the best protective capacity due to its strongest antioxidant activity.In conclusion,quercetin compounds can protect against AA-induced liver injury through multiple pathways of oxidative stress,autophagy and apoptosis,and their protective capacity correlates with antioxidant activity.展开更多
基金Funded by the Key Technologies Research and Development Program(No.2021YFC28000900)the National Natural Science Foundation of China(No.52374178)the Collaborative Innovation Project of Colleges and Universities of Anhui Province(No.GXXT-2020-057)。
文摘A ternary early-strengthening agent consisting of calcium formate+triethanolamine+lithium sulfate was compounded with quercetin to shorten the setting time of cementitious materials while ensuring their early strength.The optimum ratio of the three early-strengthening agents was determined as 0.5%calcium formate+0.04%triethanolamine+0.4%lithium sulfate by response surface methodology.The effects of the ternary early-strengthening agent composed of calcium formate+triethanolamine(TEA)+lithium sulfate on cementitious pore sealing materials under the synergistic effect of quercetin were studied by means of the performance tests of compressive strength,fluidity,and setting time,and the microstructural characterizations of X-ray powder diffractometer(XRD),thermogravimetry(TG-DSC)and scanning electron microscopy(SEM).The study shows that the synergistic effect of ternary early-strengthening agent and quercetin forms a multi-performance composite admixture for cementitious materials.The best performance was obtained with the compounding scheme of 0.5%calcium formate+0.04%triethanolamine+0.4%lithium sulfate ternary early-strengthening agent and 0.05%quercetin.The compressive strength of 1,3,7,and 28 d are 94.8%,39.8%,42%,and 28%higher than those of the blank group,respectively.The initial time and final setting time are 41 and 57 minutes,respectively.According to the microscopic analysis,the network and fibrous C-S-H gels generated by ternary early-strengthening agents are attached to the surface promoted by quercetin,which forms skeleton support while thickening and solidifying the cement slurry,which enhances the early compressive strength of the cement-based materials.
基金supported by National Science and Technology Fundamental Resources Investigation Program of China(2019FY100700).
文摘Hyperuricemia is a prevalent metabolic disorder resulting from dysregulation of purine metabolism,often accompanied by inflammation.It is characterized by an abnormal elevation in uric acid(UA)levels.In our investigation,the combined treatment with Lactiplantibacillus plantarum DY1 and quercetin suppressed the activity of xanthine oxidase and adenosine deaminase,decreased the levels of UA,tumor necrosis factor alpha(TNF-α)and interleukin 1β(IL-β),downregulated gene expression of urate transporter 1(URAT1)and glucose transporter 9(GLUT9),and upregulated organic anion transporter 1(OAT1)and ATP-binding cassette transporter subfamily G member 2(ABCG2).The combination increased the abundance of Lactobacillus and decreased the abundance of norank_f_norank_o__Clostridia_UCG-014 and Roseburia.Metabolomics analysis revealed that the combination of probiotics and quercetin exhibited distinct metabolic pathways compared to their individual administrations.When compared to probiotics alone,the combination led to alterations in glutathione metabolism(oxidized glutathione and glutathione)as well as sphingolipid metabolism(sphingosine and sphinganine).When compared to quercetin alone,the combination resulted in variations in tryptophan metabolism(indole-3-acetamide,5-hydroxy-L-tryptophan,indoleacetaldehyde,3-(3-indolyl)-2-oxopropanoic acid,3-indoleacetic acid and 3-methylindole)along with purine metabolism(UA,xanthosine,cyclic adenosine monophosphate(cAMP),adenosine diphosphate(ADP)and adenosine monophosphate(AMP)).The subsequent fecal microbiota transplantation proved that the effect of the combination on reducing UA levels was mediated by the gut microbiota.Therefore,this new combination can be considered a promising adjuvant therapy capable of synergistically alleviating hyperuricemia.
基金Supported by the National Natural Science Foundation of China(32072749)。
文摘The purpose of this experiment was to investigate the effect and mechanism of quercetin on reproductive performance in perinatal sows.According to the similar principle of parity and body weight,24 perinatal sows were randomly divided into four treatments with six replicates,including normal control and three treatments fed by a basal diet supplemented with 0,0.025%,0.050%,and 0.075%quercetin,respectively.The feeding trial was conducted from 100 days of gestation to 28 days post-partum.Reproductive performance,colostrum composition,serum indexes of antioxidation,inflammation,hormones,and the diversity and relative abundance of fecal microflora were determined in perinatal sows.Compared with the control,quercetin significantly reduced the rate of constipation,serum content of malondialdehyde(MDA),prolactin(PRL),and progesterone(PROG),and significantly increased the content of serum estradiol(E2)and insulin-like growth factor-1(IGF-1)in colostrum of perinatal sows(P<0.05).Meanwhile,0.025%quercetin significantly increased glutathione(GSH)content in serum(P<0.05),0.050%quercetin significantly reduced the rate of backfat loss(P<0.05),and 0.075%quercetin significantly increased immunoglobulin M(IgM)content in colostrum of perinatal sows(P<0.05).In addition,0.050%and 0.075%quercetin significantly shortened estrus interval(P<0.05)and significantly increased the content of IgA and IgG in colostrum(P<0.05)and dopamine(DA)content in serum of perinatal sows(P<0.05).Quercetin significantly decreased the content of nitric oxide(NO),IL-1β,IL-6,TNF-α,and MCP-1 in serum(P<0.05)and significantly improved microflora abundance and diversity in feces of perinatal sows(P<0.05).In conclusion,dietary supplementation of quercetin reduced oxidative stress and inflammatory responses and regulated intestinal microflora in perinatal sows,thus improved reproductive performance in perinatal sows.Under this experimental condition,the optimal supplementation with dietary quercetin was 0.075%in perinatal sows.
基金the Innovation and Demonstration of Industry and Education Integration in Feed Industrial Chain Transformation and Upgradation, Sichuan Province, Chinathe National Key R&D Program of China (Grant No. 2022YFD1600902-4)+3 种基金the National Natural Science Foundation of China (Grant No. 32272870 & 32350410427)the Sichuan Province Central Guided Local Science and Technology Development Special Programme (Grant No. 23ZYZYTS0346)the Sichuan Provincial Natural Science Foundation Outstanding Youth Science Fund Project (Grant No. 24NSFJQ0121)Breeding, Development, and Healthy Breeding of Plum Blossom Chickens in the Bazhong Mountains, a City School Cooperation Project in Bazhong City.
文摘Background Granulosa cell(GC)apoptosis,ferroptosis,and other programmed cell death processes are markers of follicular aging.Quercetin has been shown to reduce ferroptosis,however,its effects on ferroptosis in poultry remains unexplored.Our preliminary study identified ferroptosis in aging ovaries.Therefore,in the present study,540-day-old Mountain Plum-blossom chickens were fed with quercetin supplementation at varying doses(0.2,0.4,and 0.6 g/kg),and examined its molecular effects on GC ferroptosis using an in vitro Erastin-induced model.Results The results showed that quercetin supplementation significantly increased egg production,which confirmed its potential to alleviate ferroptosis in chicken ovarian tissue.The in vitro experiment revealed that quercetin and Fer-1(positive control)mitigated Erastin-induced ferroptosis in GCs.Further,transcriptome analysis revealed that querce-tin modulated key genes such as acyl-CoA synthetase long-chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11),and transferrin receptor(TFRC),involved in ferroptosis regulation.The results further showed that quercetin also reduced Erastin-induced apoptosis and inflammation by modulating the expression of genes and proteins related to apoptosis and inflammatory factors(NF-κB,TNF-α,IL-6,and IL-10).Conclusion Taken together,the results showed that quercetin improves egg production performance in chickens and mitigates ovarian ferroptosis in aging hens,and inhibits Erastin-induced ferroptosis,inflammation,and apoptosis in GCs.These findings revealed the protective role of quercetin in poultry ovarian tissue and its cellular mechanisms against detrimental factors in poultry production.
基金financially supporting this work through the Large Research Group Project under grant number R.G.P.2/510/45。
文摘Background:Neurodegenerative diseases(NDs),including Alzheimer‘s disease,Parkinson‘s disease,and Huntington‘s disease,are complex and challenging due to their intricate pathophysiology and limited treatment options.Methods:This review systematically sourced articles related to neurodegenerative diseases,neurodegeneration,quercetin,and clinical studies from primary medical databases,including Scopus,PubMed,and Web of Science.Results:Recent studies have included quercetin to impact the cellular and molecular pathways involved in neurodegeneration.Quercetin,a flavonoid abundant in vegetables and fruits,is gaining attention for its antioxidant,anti-inflammatory,and antiapoptotic properties.It regulates signaling pathways such as nuclear factor-κB(NF-κB),sirtuins,and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt).These pathways are essential for cellular survival,inflammation regulation,and apoptosis.Preclinical and clinical studies have shown that quercetin improves symptoms and pathology in neurodegenerative models,indicating promising outcomes.Conclusions:The study explores the potential of incorporating laboratory research into practical medical treatment,focusing on quercetin‘s neuroprotective effects on NDs and its optimal dosage.
基金supported by National Natural Science Foundation of China(Grant 82274541&81674008)Key Project of Hunan Provincial Health Commission(Grant 202204072465)Natural Science Foundation of Hunan Province(Grant 2020JJ4070).
文摘Objective:Limb ischemia-reperfusion injury(LIRI)may lead to tissue necrosis and loss of function,even life-threatening.Our previous study found that Tao-Hong-Si-Wu decoction(THSWD)had some efficacy in treating of LIRI.Quercetin,the major component of THSWD,was selected further to uncover the molecular mechanism underlying its treatment of LIRI.Methods:In this study,myoblasts were isolated fromrat gastrocnemiusmuscle tissue,and an in vitro LIRI model was established.The cell counting kit-8(CCK-8)and colony formation assay were used to evaluate the impact of quercetin on LIRI-induced myoblast viability and proliferation.Lactate dehydrogenase(LDH)activity wasmeasured to detectmyoblast injury in the LIRI model.Theapoptosis ofmyoblasts was evaluated byHoechst staining and flow cytometry.In addition,molecular docking analysis was performed to predict the interaction between quercetin and NADPH oxidase 2(NOX-2).Subsequently,we investigated the molecular mechanism of quercetin in LIRI-induced myoblasts by overexpressing NOX-2.Results:The myogenic marker Desmin was highly expressed in isolatedmyoblasts.In the LIRImodel,myoblast viability and proliferation were decreased,and cell injury and apoptosis levels were increased.In addition,NOX-2 was highly expressed in the LIRI model.At the same time,LIRI induction promoted the up-regulation of oxidative stress and inflammatory response.Quercetin significantly reversed the effects of LIRI treatment on myoblasts in a concentration-dependent manner.Molecular docking suggested an interaction between quercetin and NOX-2.Further overexpression of NOX-2 inhibited the effect of quercetin on LIRI-induced myoblasts.Conclusion:Quercetin could reduce inflammatory response and oxidative stress by inhibiting NOX-2,thus playing a therapeutic role in treating LIRI.
文摘BACKGROUND Schizophrenia is a complex psychiatric disorder with significant functional impairment.Although olanzapine is effective in treating positive symptoms,its efficacy against negative symptoms and cognitive deficits is limited.Yueju pill,a traditional Chinese herbal formula,has shown potential in improving these domains,but its mechanisms remain largely unexplored.AIM To evaluate the therapeutic efficacy and underlying mechanisms of Yueju pill combined with olanzapine in treating schizophrenia.METHODS Ninety-seven patients with schizophrenia were randomly assigned to an intervention group(n=48)receiving olanzapine and Yueju pill,or a control group(n=49)receiving olanzapine and a placebo for 8 weeks.Symptom severity was assessed using the positive and negative syndrome scale,the scale for the assessment of negative symptoms,and cognitive and social function scales.Serum levels of brain-derived neurotrophic factor(BDNF),dopamine(DA),and serotonin(5-HT)were measured.Network pharmacology analysis identified key chemical components and target genes involved in the treatment response.RESULTS The intervention group demonstrated a significantly higher overall efficacy rate(93.75%)compared to the control group(73.47%,P<0.05).Improvements in psychiatric symptoms,cognitive function,and social performance were more pronounced in the intervention group.Additionally,serum levels of BDNF,DA,and 5-HT were significantly higher in the intervention group(P<0.05).Network pharmacology analysis revealed quercetin as a key component,modulating genes such as CHRM1,GSK3B,and KCNH2,crucial in DA signaling.CONCLUSION Yueju pill,when combined with olanzapine,significantly improves clinical outcomes in schizophrenia patients,with safety comparable to olanzapine alone.
基金supported by the Department of Education of Anhui Province(2024AH051237)the Open Research Fund of State Key Laboratory of Organic Electronics and Information Displays(SKL2023002)+1 种基金the Science and Technology Innovation Guidance Project of Bengbu City(20220127)the College Students’Innovation and Entrepreneurship Training Program(202210367075,S202310367061).
文摘Background:Breast cancer ranks as the most common cancer in women globally,presenting major challenges primarily due to the emergence of resistance to existing therapies and the adverse side effects linked with these treatments.Natural compounds,such as quercetin,a flavonoid found in Artemisia annua,have gained attention for their multi-targeted therapeutic potential.This research aims to investigate the pharmacological effects of quercetin in inducing cellular senescence in breast cancer cells utilizing network pharmacology.Methods:Initially,the active compounds of Artemisia annua were identified through the Traditional Chinese Medicine Systems Pharmacology database.The breast cancer-related genes were gathered from various databases.The intersection between the genes associated with breast cancer and the targets of active pharmaceutical ingredients was analyzed.Additionally,the regulatory network of active ingredients and their targets was researched.Further,protein-protein interaction was acquired from STRING database and core targets were analyzed.The analyses of Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were conducted utilizing R programming language.Results:In Artemisia annua,18 active compounds were identified along with their associated target proteins,among which quercetin exhibiting the highest number of target proteins.2897 disease-related genes were discovered,and 145 drug-disease intersection targets were selected.The analysis focused on the impact of quercetin on cellular senescence,informed by core target analysis and enrichment results.Molecular docking studies demonstrated the stable binding of quercetin to cyclin-dependent kinase 2(CDK2),which was chosen for experimental validation.Conclusion:The research highlights the promising therapeutic efficacy of quercetin on breast cancer by the induction of cellular senescence,offering valuable biological insights and establishing a foundation for future research.
基金supported by the Guangdong Basic and Applied Basic Research Foundation under Grant(2023A1515011243)National Natural Science Foundation of China under Grant(82004141)+2 种基金Bao’an Traditional Chinese Medicine Development Foundation under Grant(2022KJCX-ZJZL-11)Science,Technology,and Innovation Commission of Shenzhen Municipality under Grant(JCYJ20190808160407500)Shenzhen Bao’an Traditional Chinese Medicine Hospital Research Program under Grant(BAZYY20220701).
文摘Background:Pulmonary fibrosis(PF)is a refractory disease with limited treatment options.This study investigates the potential anti-PF effects of the herbal formula Yiqi Huatan Sanjie(YQHTSJ)administered via nebulized inhalation,exploring its underlying mechanisms.Methods:The anti-fibrotic properties of nebulized YQHTSJ were assessed using a bleomycin(BLM)-induced PF mouse model.RNA sequencing identified differentially expressed genes(DEGs),and subsequent gene enrichment analysis,along with transcription factor(TF)prediction,revealed YQHTSJ-regulated DEGs.Active components and targets of YQHTSJ were retrieved from the HERB database,leading to the identification of key TFs interacting with DEGs.Quercetin,a constituent of YQHTSJ,was evaluated for its effects on transforming growth factor-β1-induced myofibroblast activation and BLM-induced PF.The direct binding interaction between quercetin and the key TF Jun proto-oncogene(JUN)was confirmed through molecular docking studies and the cellular thermal shift assay(CETSA)experiments.Results:Nebulized YQHTSJ was found to significantly inhibit PF and inflammation in the mouse model.RNA sequencing identified 135 DEGs regulated by YQHTSJ,and 27 key TFs associated with these DEGs were predicted.Among YQHTSJ’s potential targets,41 were identified as TFs,with six-JUN,Fos proto-oncogene,MYC proto-oncogene,RELA proto-oncogene,nuclear factor kappa B subunit 1,and peroxisome proliferator activated receptor alpha-recognized as key TFs targeted by YQHTSJ.Molecular docking and CETSA experiments confirmed that quercetin directly targets JUN protein and inhibits its phosphorylation,thereby contributing to the suppression of myofibroblast activation and PF.Conclusion:The potential mechanisms of YQHTSJ and its component quercetin in combating PF may involve the regulation of critical TFs like JUN and the suppression of pathogenic gene expression.
基金Supported by Educational Research Project for Young and Middle-aged Teachers in Fujian Province(Science and Technology Category,JAT210477)。
文摘[Objectives]To further explore the mechanism of quercetin regulating the activity of Sune-1 cells.[Methods]High-throughput mRNA-miRNA transcriptome sequencing technology was used to screen miRNA in Sune-1 cells treated with quercetin.[Results]Statistical analysis showed that 1264 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 716 were significantly up-regulated and 548 were significantly down-regulated;191 miRNAs were differentially expressed in Sune-1 cells treated with quercetin,of which 129 were significantly up-regulated and 62 were significantly down-regulated.By comparing the expression differences of these mRNAs and miRNAs in different samples,six different expression patterns were clustered.The expression of the above miRNAs was verified by real-time quantitative PCR(qPCR),and the results were highly consistent with the transcriptome sequencing data.In addition,Gene Ontology annotation and functional enrichment analysis of miRNA target genes showed that CTGF,VHL and H19,which are related to the regulation of cell proliferation signal transduction,were predicted to be new targets of differential miRNAs such as miR494-3p and miR675-3p and may play an important regulatory role in the process of Quercetin inhibiting the proliferation of Sune-1 cells.[Conclusions]This study provides a basis for the rational use of anti-tumor functional components of traditional Chinese medicine,and also provides a theoretical basis for the targeted therapy of nasopharyngeal carcinoma.
文摘Objective:To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.Methods:Four groups of 32 rats were used in this study:three groups were given streptozotocin to induce diabetes,and one group was given a normal control.For treatment groups,each group received either metformin(200 mg/kg body weight)or quercetin(50 mg/kg body weight)for a month.The expression of SREBP1c was detected by quantitative RT-PCR and fibrosis-related proteins(TGF-βand p-Smad3)was evaluated by Western blot.Furthermore,MCP and IL-1βwere determined by ELISA.Results:Quercetin significantly reduced insulin and glucose levels.Besides,it reduced the serum levels of ALT,AST,and ALP,improved lipid profile,lowered the MDA level,increased SOD activity,decreased the rise in MCP-1 and IL-1β,inhibited the TGF-β/Smad3 signaling pathway,decreasedα-SMA and SREBP1c expression,and increased AMPK(P<0.05).Conclusions:Quercetin could significantly mitigate hepatic damage by modulating the expression of pro-inflammatory cytokines and fibrosis markers.
基金supported by the National Natural Science Foundation of China(No.81970848).
文摘Quercetin is a natural compound with potent antiviral effects;however,its role in the treatment of herpes simplex keratitis(HSK)remains underexplored.Here,we investigated the antiviral effects of quercetin against herpes simplex virus 1(HSV-1).By examining different phases of viral infection in human corneal epithelial cells(HCECs),we found that 30μmol/L quercetin inhibits HSV-1 replication primarily by disrupting viral attachment.RNA-sequencing and subsequent analyses revealed that the nuclear factor E2-related factor 2(Nrf2)was upregulated by quercetin in a dose-dependent manner.Knocking down Nrf2 partially compromised quercetin's antiviral effect.Importantly,topical application of 100μmol/L quercetin alleviated HSK severity in mice,reduced viral titers in tears,and inhibited VP16 expression in the cornea and trigeminal ganglia.These findings demonstrate the antiviral effect of quercetin against HSV-1 and provide a foundation for mechanistic studies to elucidate its therapeutic potential in HSK.
基金Supported by the Science and Technology Research Project of Hubei Province,No.2021CFB210Central Guiding Local Science and Technology Development Fund Project(Science and Technology Department of Xizang Autonomous Region),No.XZ202401YD0002C。
文摘BACKGROUND Inflammatory bowel disease(IBD)is a chronic,progressive inflammatory condition of the intestine.Mesenchymal stem cell(MSC)therapy for IBD has made significant progress in recent years.To better exploit the therapeutic potential of MSCs,pretreatment strategies are employed to enhance their therapeutic capabilities.As a compound with diverse pharmacological effects,quercetin(QUR)is applied to pretreat human umbilical cord-derived MSCs(hUCMSCs)in this study,thereby augmenting their immunotherapeutic potential.AIM To evaluate the therapeutic efficacy of QUR-pretreated hUCMSCs.METHODS We induced colitis in a mouse model using a 2,4,6-trinitrobenzenesulfonic acid solution.Intraperitoneal injection of QUR-pretreated hUCMSCs significantly improved clinical and pathological manifestations of colitis compared to the model group.Interestingly,the therapeutic effect was superior to that of untreated hUCMSCs.Mice exhibited significantly reduced weight loss,diminished infiltration of inflammatory cells observed in hematoxylin and eosin staining,improved Disease Activity Index and Histological Activity Index scores.Furthermore,colonic tissue analysis revealed a significant upregulation of the anti-inflammatory cytokine interleukin 10(IL-10),accompanied by a downregulation of the pro-inflammatory cytokine IL-6.Further tests also suggested that QUR pretreatment led to inhibition of Janus kinase/signal transducer and activator of transcription(STAT)phosphorylation.RESULTS Our study demonstrated that QUR pretreatment of hUCMSCs significantly enhanced their immune-regulatory capacity.This approach effectively mitigated colonic inflammation in a mouse colitis model by modulating the IL-10/Janus kinase/STAT signaling pathway.CONCLUSION These findings suggest that QUR pretreatment acts synergistically to augment the inherent anti-inflammatory and immune-regulatory properties of hUCMSCs,resulting in enhanced therapeutic efficacy for IBD treatment.
基金supported by the National Natural Science Foundation of China(82172182 and 82102311)Natural Science Foundation of Jiangsu Province(BK20211136)+2 种基金China Postdoctoral Science Foundation(2018M643890 and 2020M683718)Xuzhou Science and Technology Project(KC21215 and KC22136)Development Fund Project of Affiliated Hospital of Xuzhou Medical University(XYFY202232)。
文摘BACKGROUND:Sepsis-related acute respiratory distress syndrome(ARDS)has a high mortality rate,and no effective treatment is available currently.Quercetin is a natural plant product with many pharmacological activities,such as antioxidative,anti-apoptotic,and anti-inflammatory effects.This study aimed to elucidate the protective mechanism of quercetin against sepsis-related ARDS.METHODS:In this study,network pharmacology and in vitro experiments were used to investigate the underlying mechanisms of quercetin against sepsis-related ARDS.Core targets and signaling pathways of quercetin against sepsis-related ARDS were screened and were verified by in vitro experiments.RESULTS:A total of 4,230 targets of quercetin,360 disease targets of sepsis-related ARDS,and 211 intersection targets were obtained via database screening.Among the 211 intersection targets,interleukin-6(IL-6),tumor necrosis factor(TNF),albumin(ALB),AKT serine/threonine kinase 1(AKT1),and interleukin-1β(IL-1β)were identified as the core targets.A Gene Ontology(GO)enrichment analysis revealed 894 genes involved in the inflammatory response,apoptosis regulation,and response to hypoxia.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis identified 106 pathways.After eliminating and generalizing,the hypoxia-inducible factor-1(HIF-1),TNF,nuclear factor-κB(NF-κB),and nucleotide-binding and oligomerization domain(NOD)-like receptor signaling pathways were identified.Molecular docking revealed that quercetin had good binding activity with the core targets.Moreover,quercetin blocked the HIF-1,TNF,NF-κB,and NODlike receptor signaling pathways in lipopolysaccharide(LPS)-induced murine alveolar macrophage(MH-S)cells.It also suppressed the inflammatory response,oxidative reactions,and cell apoptosis.CONCLUSION:Quercetin ameliorates sepsis-related ARDS by binding to its core targets and blocking the HIF-1,TNF,NF-κB,and NOD-like receptor signaling pathways to reduce inflammation,cell apoptosis,and oxidative stress.
基金National Natural Science Foundation of China(Grant No.82305214)Hunan Province’s Natural Science Fund(Grant No.2023JJ40401)+2 种基金Hunan Administration of Traditional Chinese Medicine(Grant No.B2023024)Hunan Provincial Department of Education Outstanding Youth Project(Grant No.22B0394)State Key Laboratory Project of Chinese Medicine Powder and Innovative Drugs Project(Grant No.21PTKF1002).
文摘This study delved into the mechanism by which the principal component of Astragali Radix regulated ferroptosis in the context of hypoxia-induced pulmonary hypertension,employing a combination of network pharmacology and experimental validation techniques.Active constituents of Astragali Radix and their corresponding targets were identified using the TCMSP database,while therapeutic targets associated with hypoxia-induced pulmonary hypertension were sourced from the GeneCards database.The Venn online tool facilitated the identification of overlapping targets between the active constituents of Astragali Radix and hypoxia-induced pulmonary hypertension.Interaction network diagrams depicting the relationship between Astragali Radix’s active constituents and their targets were constructed using Cytoscape software,with core targets and sub-networks identified using the CytoHubba plug-in.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted using the DAVID database.Additionally,the FerrDb database was consulted to analyze genes implicated in regulating ferroptosis.The investigation revealed 18 active constituents selected from Astragali Radix,with quercetin emerging as the key component.A total of 35 potential targets associated with Astragali Radix in regulating ferroptosis and addressing hypoxia-induced pulmonary hypertension were predicted.Experimental validation demonstrated that quercetin could inhibit the MAPK signaling pathway,resulting in reduced Fe2+and lipid peroxide levels,increased GPX4 expression,and the reversal of ferroptosis.In summary,this study elucidated the fundamental constituents and pivotal signaling pathways through which Astragali Radix modulated ferroptosis and mitigated hypoxia-induced pulmonary hypertension.Specifically,quercetin,a core constituent of Astragali Radix,was observed to inhibit ferroptosis in pulmonary arterial smooth muscle cells via the MAPK pathway and alleviate hypoxia-induced pulmonary hypertension.
基金supported by the Key Talent Project of Gansu Provincial Party Committee Organization Department Funding,China(2023RCXM23)the Industrial Support of Gansu Provincial Department of Education Funding,China(2021CYZC-55)the Key Research and Development Projects of Gansu Provincial Funding,China(21YF5NA090)。
文摘Salt stress is a typical abiotic stress in plants that causes slow growth,stunting,and reduced yield and fruit quality.Fertilization is necessary to ensure proper crop growth.However,the effect of fertilization on salt tolerance in grapevine is unclear.In this study,we investigated the effect of nitrogen fertilizer(0.01 and 0.1 mol L^(-1)NH_(4)NO_(3))application on the salt(200 mmol L^(-1)NaCl)tolerance of grapevine based on physiological indices,and transcriptomic and metabolomic analyses.The results revealed that 0.01 mol L^(-1)NH_(4)NO_(3) supplementation significantly reduced the accumulation of superoxide anion(O_(2)^(-)·),enhanced the activities of superoxide dismutase(SOD)and peroxidase(POD),and improved the levels of ascorbic acid(AsA)and glutathione(GSH)in grape leaves compared to salt treatment alone.Specifically,joint transcriptome and metabolome analyses showed that the differentially expressed genes(DEGs)and differentially accumulated metabolites(DAMs)were significantly enriched in the flavonoid biosynthesis pathway(ko00941)and the flavone and flavonol biosynthesis pathway(ko00944).In particular,the relative content of quercetin(C00389)was markedly regulated by salt and nitrogen.Further analysis revealed that exogenous foliar application of quercetin improved the SOD and POD activities,increased the AsA and GSH contents,and reduced the H_(2)O_(2) and O_(2)^(-)·contents.Meanwhile,10 hub DEGs,which had high Pearson correlations(R^(2)>0.9)with quercetin,were repressed by nitrogen.In conclusion,all the results indicated that moderate nitrogen and quercetin application under salt stress enhanced the antioxidant system defense response,thus providing a new perspective for improving salt tolerance in grapes.
基金funded by the National Natural Science Foundation of China(Grant Nos.:81503272,81630101,81891012)the Application Foundation Research Project of Sichuan Provincial Department of Science and Technology,China(Grant No.:2017JY0187)the Xinglin Scholar Research Premotion Project of Chengdu University of Traditional Chinese Medicine,China(Grant No.:2018016).
文摘Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applications of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.
基金supported in part by the Priority Academic Program Development of Jiangsu Higher Education Institutions and the State Key Laboratory of Crop Genetics and Germplasm Enhancement,China(ZW201813)。
文摘Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five different stages of R. roxburghii fruit development. Flavonoids and the genes related to their biosynthesis were found to undergo significant changes in abundance across different developmental stages, and numerous quercetin derivatives were identified. We found three gene expression modules that were significantly associated with the abundances of the different flavonoids in R. roxburghii and identified three structural UDP-glycosyltransferase genes directly involved in the synthesis of quercetin derivatives within these modules. In addition, we found that RrBEH4, RrLBD1 and RrPIF8could significantly increase the expression of downstream quercetin derivative biosynthesis genes. Taken together,these results provide new insights into the metabolism of flavonoids and the accumulation of quercetin derivatives in R. roxburghii.
基金supported by the Open Project Program of the State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science and Technology(No.SKLFNS-KF-202201)the Open Project of the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,China(No.GMU-2022-HJZ-06)。
文摘Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.
基金supported by the National Natural Science Foundation of China(32072142,31972099)Guangxi Science and Technology Base and Talent Special Projects(Guike AD21220004)。
文摘Quercetin compounds have antioxidant,anti-inflammatory and anticancer pharmacological functions.Longterm exposure to acrylamide(AA)can cause liver injury and endanger human health.However,whether quercetin compounds can attenuate AA-induced liver injury and the specific mechanism are not clear.Here,we studied the mechanism and structure-activity relationship of quercetin compounds in reducing AA-induced hepatotoxicity in vivo and in vitro.In vivo studies found that quercetin-like compounds protect against AAinduced liver injury by reducing oxidative stress levels,activating the Akt/m TOR signaling pathway to attenuate autophagy,and improving mitochondrial apoptosis and endoplasmic reticulum stress-mediated apoptosis.In vitro studies found that quercetin compounds protected Hep G2 cells from AA by attenuating the activation of AA-induced autophagy,lowering reactive oxygen species(ROS)levels by exerting antioxidant effects and thus attenuating oxidative stress,increasing mitochondrial membrane potential(MMP),and improving apoptosis-related proteins,thus attenuating AA-induced apoptosis.Furthermore,the conformational differences between quercetin compounds correlated with their protective capacity against AA-induced hepatotoxicity,with quercetin showing the best protective capacity due to its strongest antioxidant activity.In conclusion,quercetin compounds can protect against AA-induced liver injury through multiple pathways of oxidative stress,autophagy and apoptosis,and their protective capacity correlates with antioxidant activity.
