Determine the mechanisms by which quercetin increases viral clearance in COPD airways. Completion of these studies will provide important insights into mechanisms by which quercetin decreases airway inflammation, goblet cell metaplasia and viral clearance in chronic obstructive lung disease.

These studies are required to determine the suitability of quercetin as an alternative complimentary medicine in the management of COPD lung disease. Chronic obstructive pulmonary disease COPD is the third leading cause of death in the U.

Quercetin, a dietary flavanol found in foods such as apples, berries and onions has potent antioxidant and anti-inflammatory properties. Our published preclinical studies suggest that quercetin improves lung function and reduces lung inflammation, but the underlying mechanisms are not well known.

The goal of this application is to perform mechanistic studies to understand how quercetin treatment improves disease outcome in COPD models. The information gained from this study will provide important insights into mechanisms by which quercetin decreases airway inflammation, mucus producing cells and viral clearance in chronic obstructive lung disease.

Toggle navigation. Home Search Services Blog Contact About. Quercetin prevents progression of COPD lung disease by modulating Foxo3A activity Sajjan, Umadevi Sivanappa University of Michigan Ann Arbor, Ann Arbor, MI, United States.

Share this grant: : :. Abstract Funding Institution Related projects Publications Comments. Recent in Grantomics:. Recently viewed grants:. Recently added grants:. Funding Agency. Project Start Project End Budget Start Budget End Support Year 1 Fiscal Year Total Cost Indirect Cost.

Name University of Michigan Ann Arbor. City Ann Arbor State MI Country United States Zip Code Related projects. Based on its polyphenol structure, quercetin has potent antioxidant effects, combining with free radical species to form considerably less reactive phenoxy radicals [ 16 , 17 ].

Previously, we demonstrated that quercetin inhibits TNF-α stimulated IL-8 expression at the transcriptional level in airway epithelial cells and decreases airways hyperresponsiveness in cockroach allergen-sensitized and challenged mice, a model of allergic airways disease, at a dose of 0.

Further, quercetin decreases the expression of MMP9 stimulated by TNF-α in epidermal cells [ 21 ]. Based on these observations, we hypothesized that quercetin reverses oxidative stress and inhibit MMP production, perhaps by increasing the expression of the histone deacetylase Sirt-1, thereby preventing the progression of lung disease in COPD.

We also determined the effect of quercetin on the histone acetylation of the MMP9 and MMP12 promoters by chromatin immunoprecipitation assay. Animals were exposed by the intranasal route to 1. coli OB6 Sigma-Aldrich, St.

Louis, MO on day four of the week for four consecutive weeks. Control mice were exposed to PBS. In some experiments, mice were treated intraperitoneally with μl PBS or PBS containing sirtinol 0.

Mice were sacrificed 1 h after the last quercetin treatment. All experiments described herein were approved by the Animal Care and Use Committee of the University of Michigan. Mice Were Anesthetized By Intraperitoneal Injection Of Ketamine 2.

To Determine Elastic Recoil, Lungs Were Gradually Inflated To 30 Cm H 2 O And Pressure And Lung Volume Measured Continuously During Inflation And Deflation Of The Lungs. Static Elastance And Compliance Were Recorded By Inflating The Lungs To Full Capacity. Alveolar Chord Length Was Determined Using Sagittal Sections Obtained At 5 Mm Intervals Through The Length Of The Lungs, And Diameter Of The Airspaces Was Measured In Random Areas Using Nih Image J Analysis Software [ 15 ].

Mice Were Euthanized And Lungs Were Lavaged With Pbs. Bal Fluid Was Centrifuged And The Supernatant Was Collected For Determination Of Mmp Levels.

Total And Differential Cell Counts In Bal Fluid Were Determined As Described Previously [ 15 , 22 ]. After Relevant Treatment, Mice Were Euthanized, Lungs Were Collected, Homogenized In Pbs Containing Complete Protease Inhibitors And Centrifuged Roche, Indianapolis, In.

To Determine The Effect Of Quercetin On Mmp Expression, Cells Were Seeded In 6 Well Plates And Grown For 24 H. In Between Exposures To Lps, Cells Were Maintained In Cell Culture Media Alone.

Cells Were Then Shifted To Serum-Free Media Containing Quercetin Dihydrate Or Dmso, Incubated For 24 H, And Media And Cells Were Harvested. Cells Exposed To Media Alone Instead Of Lps Were Used As Negative Controls. Mmp Activity Was Determined By Gelatin Zymography As Described. Mice Were Sacrificed And Blood Was Collected By Cardiac Puncture In Tubes With Anticoagulant, Centrifuged And Plasma Was Collected.

Levels Of Quercetin In Plasma Were Determined By Hplc As Described Previously [ 19 ]. Chip Assays Were Performed With A Chip-It Kit Active Motif, Carlsbad, Ca Following The Manufacturer'S Instructions. Briefly, Cells Were Fixed, Lysed And Chromatin Was Subjected To Enzymatic Shearing.

Chromatin Fragments Of Bp Were Immunoprecipitated With An Antibody To Acetylhistone H4 Antibody. Chip And Input Dna Were Purified And Subjected To Qpcr Using Primers Specific For The Nf-κB Binding Site In The Mmp9 And Mmp12 Promoters. Qpcr Conditions Were As Follows: 95°C For 15 Minutes; 95°C For 10 Seconds, 60°C For 30 Seconds, 72°C For 30 Seconds, Repeated For 50 Cycles, 72°C For 10 Minutes.

Expression Of Mmp9 , Mmp12 , Sirt1 , Inducible Nitric Oxide Synthase Inos , Heme Oxygenase Hmox -1 , And Muc5Ac Was Determined By Qpcr. All Pcr Reactions Were Performed In An Eppendorf Mastercycler Westbury, Ny And Gene Expression Was Quantified Using The Comparative Ct Method.

Nuclear Proteins Were Resolved By 7. The Amount Of Lipid Peroxidation Products In The Lungs Was Assayed As Thiobarburtic Acid Reacting Substances Tbars Cell Biolabs, San Diego, Ca Following Manufacturer'S Instructions.

Statistical Analysis Of Significance Was Calculated By One-Way Analysis Of Variance Followed By Tukey'S Post Hoc Test, Anova On Ranks With Dunn'S Post Hoc Analysis Or By Mann-Whitney Test As Appropriate. Results Represent Mean ± Sd Or Sem, Or Range Of Data With Median. This situation is analogous to the further progression of emphysema in COPD patients even after cessation of smoking [ 24 ].

Quercetin partially improves lung function in elastase-LPS exposed mice. Mice were anesthetized and pressure-volume relationships, compliance and elastance were measured using flexivent system. Chord length was determined by morphometry.

Representative PV curves from 5 to 6 mice from each group are shown in A and B. Next, we examined the lung function of mice treated with quercetin 0. Compared to vehicle, mice receiving quercetin showed a rightward and downward shift in their volume-pressure curve Figure 1B.

Shifts in the pressure-volume loops were accompanied by appropriate changes in elastance and compliance Figures 1C and 1D.

Finally, compared to vehicle, quercetin treatment was associated with a reduction in alveolar chord length Figure 1E. Quercetin treatment did not affect any of these measurements in the lungs of mice exposed to PBS.

Compared to vehicle, quercetin treatment significantly decreased the levels of all chemokines and pro-inflammatory cytokines examined. PBS-exposed mice treated with quercetin showed similar levels of all cytokines measured compared to mice treated with vehicle data not shown.

Quercetin treatment reduces all the examined cytokines and chemokines. Quercetin treatment reduces lung inflammation and reverses goblet cell metaplasia. A and B. Mice treated with vehicle show mild-to-moderate wide-spread lung inflammation, emphysema and goblet cell metaplasia.

C and D. Mice treated with quercetin show less emphysema with very mild inflammation and a complete reduction in MUC5AC producing goblet cells. Asterisks in A and C represent emphysema.

Arrows in B indicate MUC5AC- producing goblet cells. Images are representative of 6 mice per group. Lung MMP levels did not change in quercetin treated PBS-exposed mice data not shown.

mRNA expression of Mmp9 , Mmp12 , and Sirt1 was measured by qPCR. MMP activity was determined by gelatin zymography. Sirt1 protein level was measured in the lung homogenates by Western blot analysis.

D and E. Images in C and E are representative of 4 to 6 animals per group. MMP9 transcription is negatively regulated by a histone deacetylase, SIRT1 2.

These results suggest that quercetin may suppress MMP9 and MMP12 expression by increasing Sirt1 levels. Sirtinol treatment also blocked the improvements of elastic recoil, static compliance and static elastance induced by quercetin. These results are consistent with the notion that quercetin exerts its effects by increasing Sirt1 levels, which negatively regulate MMP expression.

Inhibition of Sirt1 activity in quercetin-treated mice attenuates querecetin-induced changes in MMP expression and emphysema progression. Mice treated with quercetin and sirtinol did not show reduced MMP9 or MMP12 mRNA expression.

Sirtinol also inhibited quercetin's effects on elastic recoil C , compliance D and elastance E. Representative of animals per group. Chromatographic analysis of plasma obtained from mice treated with 0. Quantification of the major peak indicated a mean plasma quercetin level of 0.

This level was significantly higher than the quercetin level observed in vehicle-treated mice 0. Sirt1, a histone deacetylase, negatively regulates MMP9 transcription by deacetylating histone H4 in the promoter region NF-κB binding site [ 7 ].

To determine whether quercetin increases H4 deacetylation at this site, we employed an in vitro cell culture system. Murine alveolar macrophages exposed to low levels of LPS for three days showed increased Mmp9 and Mmp12 mRNA levels, with a concomitant decrease in Sirt1 expression Figure 7A-C.

We also observed increased MMP9 activity Figure 7D and decreased SIRT1 protein expression Figure 7E and 7F in LPS-treated alveolar macrophages. Consistent with these in vivo results, in vitro quercetin treatment of alveolar macrophages significantly decreased LPS-induced mRNA expression of Mmp9 and Mmp12 as well as MMP9 activity, while increasing mRNA and protein expression of Sirt1.

Next, we examined whether quercetin increases histone deacetylation of the MMP9 and MMP12 promoter NF-κB binding sites by ChIP assay. Histone H4 acetylation at the MMP9 and MMP12 promoter NF-κB binding sites was increased in LPS-exposed alveolar macrophages compared to media-treated controls, and this was completely inhibited by treatment with quercetin Figures 7G and 7H.

These results suggest that quercetin inhibits H4-acetylation of MMP promoters by increasing Sirt-1 expression, thereby regulating MMP expression at the transcriptional level. Quercetin decreases MMP9 and MMP12 and increases Sirt1 in LPS-treated alveolar macrophages.

LPS treatment induced mRNA expression of MMP9 and MMP12 which are partially reversed by quercetin. C and E. Quercetin increases Sirt1 mRNA and protein expression.

MMP9 activity in LPS-exposed was abrogated by quercetin treatment. A representative Western blot showing Sirt1 and β-actin expression.

G and H. Quercetin decreased LPS-induced histone H4 acetylation at the NF-κB binding sites in the promoter regions of both Mmp9 and Mmp Zymogram and immunoblot images are representative of three independent experiments. Quercetin also decreases MMP9 and MMP12 levels by increasing expression of the type III protein deacetylase Sirt-1, a negative regulator of MMP transcription both in vivo and in vitro.

In this study, mice were exposed to elastase and LPS, rather than cigarette smoke, the primary trigger of COPD in industrialized nations. This published murine model system [ 15 ] produces structural and functional features that are more pronounced and more typical of human COPD than can be achieved in wild type mice by even prolonged exposures to tobacco-smoke alone.

These changes include not only pulmonary emphysema, loss of lung elastic recoil, hyperinflation, but also diffuse lung inflammation, goblet cell metaplasia, airway remodeling and markedly increased numbers of neutrophils, T and B lymphocytes, monocytes and immature macrophages in the airways and alveoli [ 15 ].

By contrast, mice exposed to cigarette smoke develop pulmonary emphysema and accumulation of alveolar macrophages, but fail to demonstrate chronic bronchitis or goblet cell metaplasia [ 29 ]. Moreover, LPS is a significant constituent of cigarette smoke [ 9 , 10 ].

Epidemiologic studies of COPD patients have suggested an association of polyphenol intake with improved symptoms, as assessed by cough, sputum production, breathlessness and improved lung function, as measured by FEV 1 [ 33 — 35 ].

Several in vitro and in vivo studies also have showed a direct impact of polyphenols in reducing oxidative stress and inflammation. For instance, resveratrol, a component of red wine, decreased inflammatory cytokine production from macrophages isolated from COPD patients [ 36 ] and induced synthesis of reduced glutathione by activating NF-E2-related factor Nrf -2, a key antioxidant transcription factor in human lung epithelial cells [ 37 ].

Curcumin, another well-studied polyphenol, has also been reported to inhibit activation of NF-κB in vitro and inflammation in vivo and restore glucocorticoid efficacy in response to oxidative stress by upregulation of HDAC2 activity in macrophages [ 38 — 40 ]. Curcumin also increased synthesis of Nrf2-dependent phase II antioxidant enzymes in elastase and cigarette smoke- exposed mice [ 41 ].

TBARS, products of lipid peroxidation and an index of oxidative stress caused by reactive oxygen species, have been shown to be increased in COPD patients [ 30 ]. In addition, the number of HMOX-1 expressing alveolar macrophages is markedly decreased in patients with severe COPD, while iNOS expression is increased in alveolar and bronchial epithelial cells [ 42 ].

Increased staining for the nitration marker nitrotyrosine in iNOS positive cells was observed in induced sputum from patients with moderate stable COPD compared to nonsmokers [ 43 ].

Finally, overexpression of HMOX-1 in mouse lungs was shown to suppress elastase-induced emphysema by attenuating neutrophilic inflammation [ 44 ]. Consistent with our observation, quercetin was noted to inhibit iNOS expression and NO production in LPS and interferon-γ-treated mouse BV-2 microglial cells, and this was associated with elevated expression of Hmox-1 [ 45 — 47 ].

In addition to its antioxidant effects, quercetin may attenuate lung inflammation by inhibition of protein and lipid kinases involved in inflammatory cytokine and chemokine production.

Quercetin has inhibitory effects on phosphatidylinositol 3-kinase, AMP-activated kinase, casein kinase 2, p90 ribosomal protein S6 kinase, p70 ribosomal S6 kinase [ 49 ], protein kinase C [ 50 ], epidermal growth factor receptor tyrosine kinase [ 51 ] and IκB kinase [ 52 ].

Indeed, the design of the synthetic PI 3-kinase inhibitor LY was based on the structure of quercetin [ 53 ]. MMP expression is increased in COPD patients and plays a critical role in development and progression of emphysema. MMP also increases mucin production, leading to airway obstruction [ 54 — 58 ].

Further, levels of Sirt1, a type III histone deacetylase which negatively regulates MMP9 transcription [ 7 ], were reported to be downregulated in patients with severe COPD but not in healthy smokers, suggesting a role for endogenous oxidative stress from activated neutrophils and macrophages in the reduction of Sirt1 [ 7 ].

Further, treatment of cigarette smoke-exposed mice with Sirt1 activator blocked MMP9 expression and pulmonary neutrophilic inflammation. Interestingly, we also found decreased levels of the protein deacetylase Sirt1 in these mice. Consistent with this, we observed that, in alveolar macrophages.

quercetin decreases LPS-induced histone H4 acetylation at the MMP9 and MMP12 promoter NF-κB binding sites, thereby decreasing the transcription of MMP9 and MMP Together, these data suggest that quercetin prevents further degradation of alveolar walls by decreasing MMP expression, thereby slowing the progression of emphysema in these mice.

For example, we showed that 0. At this dose, quercetin levels of 0. In the present study, plasma quercetin levels of 0. This dose was well-tolerated and was sufficient to prevent progression of emphysema. Our previous study showed that quercetin concentrations as low as 0.

It is also possible that enteral administration of quercetin produces sufficient gut levels to modulate lung inflammation, perhaps by altering the microbiome. Normally, human quercetin plasma concentrations are in the low nanomolar range, but upon supplementation it may increase to the high nanomolar or low micromolar range [ 60 ], suggesting that the concentration of quercetin required to prevent progression of emphysema can be achieved in humans.

It is possible that absorption and availability can be further increased by using glycosylated form of quercetin [ 61 ]. These levels of quercetin were reported to be safe in humans with no adverse effects reviewed in [ 62 ].

On the other hand, a handful of in vitro studies suggested that quercetin metabolites may be harmful and in fact may increase oxidative stress in lung epithelial cells [ 63 , 64 ].

Further studies are needed to determine the appropriate dosage and form of quercetin glycosylated versus aglycosylated for administration to human patients.

Quercetin also prevented progression of emphysema in these mice. Even after cessation of smoking, COPD patients show progressive emphysematous changes due to persistent oxidative stress and protease burden in the airways [ 24 ].

The possibility that quercetin, which reduces inflammation and MMP levels while preventing progression of emphysema, may be beneficial in patients with COPD merits clinical testing.

Rahman I, Adcock IM: Oxidative stress and redox regulation of lung inflammation in COPD. Eur Respir J , — Article CAS PubMed Google Scholar. MacNee W, Rahman I: Is oxidative stress central to the pathogenesis of chronic obstructive pulmonary disease? Trends Mol Med , 7: 55— Sydbom A, Blomberg A, Parnia S, Stenfors N, Sandstrom T, Dahlen SE: Health effects of diesel exhaust emissions.

Nowak D, Kasielski M, Antczak A, Pietras T, Bialasiewicz P: Increased content of thiobarbituric acid-reactive substances and hydrogen peroxide in the expired breath condensate of patients with stable chronic obstructive pulmonary disease: no significant effect of cigarette smoking.

Respir Med , — Chung KF, Adcock IM: Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, Barczyk A, Hayashi S, Adcock IM, Hogg JC, et al.

N Engl J Med , — Nakamaru Y, Vuppusetty C, Wada H, Milne JC, Ito M, Rossios C, Elliot M, Hogg J, Kharitonov S, Goto H, et al. FASEB J , — Hasday JD, Bascom R, Costa JJ, Fitzgerald T, Dubin W: Bacterial endotoxin is an active component of cigarette smoke.

Chest , — Larsson L, Szponar B, Pehrson C: Tobacco smoking increases dramatically air concentrations of endotoxin. Indoor Air , — Sebastian A, Pehrson C, Larsson L: Elevated concentrations of endotoxin in indoor air due to cigarette smoking.

J Environ Monit , 8: — Jagielo PJ, Thorne PS, Watt JL, Frees KL, Quinn TJ, Schwartz DA: Grain dust and endotoxin inhalation challenges produce similar inflammatory responses in normal subjects. Michel O, Duchateau J, Plat G, Cantinieaux B, Hotimsky A, Gerain J, Sergysels R: Blood inflammatory response to inhaled endotoxin in normal subjects.

Clin Exp Allergy , 73— Kaneko Y, Takashima K, Suzuki N, Yamana K: Effects of theophylline on chronic inflammatory lung injury induced by LPS exposure in Guinea pigs. Allergol Int , — Vernooy JH, Dentener MA, van Suylen RJ, Buurman WA, Wouters EF: Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology.

Am J Respir Cell Mol Biol , — Sajjan U, Ganesan S, Comstock AT, Shim J, Wang Q, Nagarkar DR, Zhao Y, Goldsmith AM, Sonstein J, Linn MJ, et al. Am J Physiol Lung Cell Mol Physiol , L— Article CAS PubMed PubMed Central Google Scholar.

Kandaswami C, Middleton E Jr: Free radical scavenging and antioxidant activity of plant flavonoids. Adv Exp Med Biol , — Robak J, Gryglewski RJ: Flavonoids are scavengers of superoxide anions.

Biochem Pharmacol , — Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, Williams RL: Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY, quercetin, myricetin, and staurosporine.

Mol Cell , 6: — Nanua S, Zick SM, Andrade JE, Sajjan US, Burgess JR, Lukacs NW, Hershenson MB: Quercetin blocks airway epithelial cell chemokine expression.

Rogerio AP, Kanashiro A, Fontanari C, da Silva EV, Lucisano-Valim YM, Soares EG, Faccioli LH: Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma.

Inflamm Res , — Hwang MK, Song NR, Kang NJ, Lee KW, Lee HJ: Activation of phosphatidylinositol 3-kinase is required for tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase its direct inhibition by quercetin. Int J Biochem Cell Biol , — Newcomb DC, Sajjan US, Nagarkar DR, Wang Q, Nanua S, Zhou Y, McHenry CL, Hennrick KT, Tsai WC, Bentley JK, et al.

Am J Respir Crit Care Med , — Mercer PF, Shute JK, Bhowmik A, Donaldson GC, Wedzicha JA, Warner JA: MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation. Respir Res , 6: Louhelainen N, Rytila P, Haahtela T, Kinnula VL, Djukanovic R: Persistence of oxidant and protease burden in the airways after smoking cessation.

BMC Pulm Med , 9: Article PubMed PubMed Central Google Scholar. Finlay GA, O'Driscoll LR, Russell KJ, D'Arcy EM, Masterson JB, FitzGerald MX, O'Connor CM: Matrix metalloproteinase expression and production by alveolar macrophages in emphysema.

Segura-Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M: Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ Jr, Chapman HA Jr, Shapiro SD, Elias JA: Inducible targeting of IL to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema.

J Clin Invest , — Hwang JW, Chung S, Sundar IK, Yao H, Arunachalam G, McBurney MW, Rahman I: Cigarette smoke-induced autophagy is regulated by SIRT1-PARPdependent mechanism: Implication in pathogenesis of COPD. Aarch Biochem Biophy , — Article CAS Google Scholar.

Tabak C, Arts IC, Smit HA, Heederik D, Kromhout D: Chronic obstructive pulmonary disease and intake of catechins, flavonols, and flavones: the MORGEN Study. Am J Respir Crit Care Med , 61— Santus P, Sola A, Carlucci P, Fumagalli F, Di Gennaro A, Mondoni M, Carnini C, Centanni S, Sala A: Lipid peroxidation and 5-lipoxygenase activity in chronic obstructive pulmonary disease.

Article PubMed Google Scholar. Walda IC, Tabak C, Smit HA, Rasanen L, Fidanza F, Menotti A, Nissinen A, Feskens EJ, Kromhout D: Diet and year chronic obstructive pulmonary disease mortality in middle-aged men from three European countries.

Eur J Clin Nutr , — Culpitt SV, Rogers DF, Fenwick PS, Shah P, De Matos C, Russell RE, Barnes PJ, Donnelly LE: Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD. Thorax , — Kode A, Rajendrasozhan S, Caito S, Yang SR, Megson IL, Rahman I: Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells.

Biswas SK, McClure D, Jimenez LA, Megson IL, Rahman I: Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity. Meja KK, Rajendrasozhan S, Adenuga D, Biswas SK, Sundar IK, Spooner G, Marwick JA, Chakravarty P, Fletcher D, Whittaker P, et al.

Shishodia S, Potdar P, Gairola CG, Aggarwal BB: Curcumin diferuloylmethane down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1.

Layout table for study information Study Type : Interventional Clinical Trial Actual Enrollment : 9 participants Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple Participant, Care Provider, Investigator Primary Purpose: Treatment Official Title: Phase I Study to Determine the Safety of Quercetin in COPD Patients Study Start Date : February Actual Primary Completion Date : October Actual Study Completion Date : October Resource links provided by the National Library of Medicine MedlinePlus related topics: COPD Lung Diseases Drug Information available for: Quercetin Genetic and Rare Diseases Information Center resources: Chronic Graft Versus Host Disease U.

COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take one of the following for 1 week. Note: If values for any of the measures indicated here were found, the participant would be indicated as a participant with a safety concern, and values for that particular measure would be posted specifically, but since none of the participants experienced these outlying values, results of all tests are expressed here as a composite function.

Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.

To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. Layout table for eligibility information Ages Eligible for Study: 40 Years to 80 Years Adult, Older Adult Sexes Eligible for Study: All Accepts Healthy Volunteers: No Criteria Inclusion Criteria:.

This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials. gov instead. Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information.

Search for terms. gov PRS Why Should I Register and Submit Results? FDAAA and the Final Rule How to Apply for a PRS Account How to Register Your Study How to Edit Your Study Record How to Submit Your Results Frequently Asked Questions Support Materials Training Materials Resources Selected Publications Clinical Alerts and Advisories RSS Feeds Trends, Charts, and Maps Downloading Content for Analysis About Site What's New ClinicalTrials.

gov Background About the Results Database History, Policies, and Laws ClinicalTrials. Find Studies New Search Advanced Search See Studies by Topic See Studies on Map How to Search How to Use Search Results How to Find Results of Studies How to Read a Study Record About Studies Learn About Studies Other Sites About Studies Glossary of Common Site Terms Submit Studies Submit Studies to ClinicalTrials.

Home Search Results Study Record Detail Saved Studies. Save this study. Warning You have reached the maximum number of saved studies Beneficial Effects of Quercetin in Chronic Obstructive Pulmonary Disease COPD Quercetin The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.

Listing a study does not mean it has been evaluated by the U. Federal Government. Read our disclaimer for details. gov Identifier: NCT Recruitment Status : Completed First Posted : October 16, Results First Posted : December 26, Last Update Posted : December 26, View this study on the modernized ClinicalTrials.

National Center for Complementary and Integrative Health NCCIH. Study Details Tabular View Study Results Disclaimer How to Read a Study Record.

Study Description. Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information.

Chronic obstructive pulmonary disease COPD is a progressive disorder of the lung parenchyma and airways, which is the third-leading cause of death in the USA.

Current therapies for COPD are only partially effective and may also have side effects. Although increasing evidence indicates that quercetin supplementation may be beneficial in treating COPD, key methodological issues have not been resolved.

The overall objective of this study is to determine the dosage of quercetin supplementation, bioavailability of quercetin, safety, dose-response relationship and appropriate biomarkers which reflect clinical outcomes in patients with COPD that is necessary for conducting large clinical trials in this patient population.

Detailed Description:. Resource links provided by the National Library of Medicine MedlinePlus related topics: COPD Lung Diseases. Drug Information available for: Quercetin. Genetic and Rare Diseases Information Center resources: Chronic Graft Versus Host Disease. FDA Resources. Arms and Interventions.

COPD Subjects will be asked to avoid quercetin rich diet for one week and then asked to take placebo sugar chew containing mg of vitamin C and 10 mg niacin. Quercetin chew containing mg quercetin, mg vitamin C and 10 mg niacin. Outcome Measures. Primary Outcome Measures : Participants Who Experienced Safety Concerns, Where Safety Concerns of Quercetin Supplementation is Indicated by Significant Change From Baseline Measures of Tests Indicated Below in Outcome Measure Description [ Time Frame: One week in Phase I safety study ] Note: If values for any of the measures indicated here were found, the participant would be indicated as a participant with a safety concern, and values for that particular measure would be posted specifically, but since none of the participants experienced these outlying values, results of all tests are expressed here as a composite function.

Eligibility Criteria. Layout table for eligibility information Ages Eligible for Study: 40 Years to 80 Years Adult, Older Adult Sexes Eligible for Study: All Accepts Healthy Volunteers: No Criteria. Contacts and Locations. Patent-pending ABB C1® redefines immune support by addressing innate, acquired, and Trained Immunity.

In 'ABB C1®: Training Now for Future Immune CONTINUE TO SITE Or wait Kaneka Ubiquinol® and Preconception Health Content provided by Kaneka Nutrients — Manufacturer and Supplier of Kaneka Ubiquinol® Feb White Paper An ally in the fight against oxidative stress, Kaneka Ubiquinol® offers antioxidant support for men and women concerned about reproductive health.

Empowering Fertility: Unlocking the Potential of Ubiquinol for Mitochondrial Health and Fertility Kaneka Ubiquinol Recorded the Nov Webinar In partnership with Kaneka Corporation, Dr Leah Hechtman PhD will delve into the science of the antioxidant ubiquinol and its profound impact on mitochondrial Fruit d'Or OmniActive Health Technologies.

Facebook Twitter Linkedin. Why botanical integrity starts with quality ingredients By Verdure Sciences Passion flower extract SIVI a clinically proven, natural ingredient for good quality sleep By JK Botanicals Private Limited Supporting body-mind wellness with whole microalgae By Solabia — Algatech Nutrition.

NutraIngredients-USA Advertise with us Apply to reuse our content Press Releases — Guidelines About us Contact the Editor Report a technical problem.

Resources Subscription Benefits Why Register Whitelist our newsletters Editorial Calendar Event Calendar RSS Feed Podcast FAQ. While no significant group differences were reported for URTI outcomes between all subjects combined, or for specific gender, BMI, or age groups, the authors do report that physically fit over 40 year olds experienced a 36 percent reduction in URTI severity and a 31 percent reduction in total URTI sick days when receiving the high dose.

Heinz, D. Henson, M. Austin, F. Jin, D. Show more. Kaneka Ubiquinol Recorded the Nov Webinar. In partnership with Kaneka Corporation, Dr Leah Hechtman PhD will delve into the science of the antioxidant ubiquinol and its profound impact on mitochondrial Patent-pending ABB C1® redefines immune support by addressing innate, acquired, and Trained Immunity.