Video
1 Vitamin Can Save Your roomroom.infothen Respiratory \u0026 Immune System - Dr Alan Mandell, DCQuercetin and respiratory health -
An elegant study involving experimental infection of COPD or normal subjects patients with RV provided direct evidence demonstrating that RV induces respiratory illness which is more severe and prolonged in COPD than in normal [ 8 ].
Further RV-infected COPD patients showed persistent expression of inflammatory cytokines, enhanced oxidative stress and accumulation of inflammatory cells in the lungs [ 8 — 10 ]. The prolonged responses were associated with relatively longer persistence and higher load of virus.
Inhaled corticosteroids, which are currently being used to treat exacerbations, modestly reduce respiratory symptoms and sometimes increases the risk for secondary bacterial infections [ 11 — 13 ]. Therefore, better therapies with relatively no side effects are needed for treatment of COPD exacerbations associated with rhinovirus infections.
Quercetin is a plant polyphenol and has potent antioxidant and anti-inflammatory properties. Previous epidemiological studies have suggested that consumption of quercetin-rich diet decreases the risk for development of asthma [ 14 ], bronchial hyper-reactivity [ 14 ] and chronic obstructive pulmonary disease [ 15 ].
Previously, we demonstrated that oral treatment with quercetin prevents further deterioration of lung function and also significantly reduces goblet cell metaplasia and lung inflammation in a mice displaying COPD-like features [ 16 ]. Additionally, we also showed that quercetin inhibits RV replication in airway epithelial cells in vitro and in a mouse model of RV infection in vivo [ 17 ].
Therefore, we hypothesized that quercetin supplementation may augment viral clearance and mitigate RV-induced pathologic changes in a mouse model of COPD. Previously we demonstrated that mice exposed to combination of cigarette smoke and heat-killed non-typeable H.
influenzae NTHi show mild to moderate emphysema, diffuse lung inflammation encompassing both conductive airways and parenchyma, and goblet cell metaplasia [ 18 ]. Following RV infection, unlike room air-exposed mice, mice exposed to combination of cigarette smoke and heat-killed NTHi mice with COPD phenotype showed persistence of virus up to 4 days post infection, enhanced lung inflammation and goblet cell metaplasia, increased expression of mucin genes and pro-inflammatory cytokines similar to that observed in RV-infected COPD patients.
In contrast, mice exposed to heat-killed NTHi or cigarette smoke alone clear virus similar to room air-exposed mice and does not induce significant changes in lung inflammation or cytokine expression following RV infection.
Based on these observations, we choose to use mice exposed to both cigarette smoke and heat-killed NTHi which display mild COPD phenotype to examine the long-term effects of rhinovirus. Since, we have already demonstrated that quercetin reduces lung inflammation and improves lung mechanics in mice displaying COPD-like features [ 16 ], and augments viral clearance and reduces RV-induced acute lung inflammation in normal mice [ 17 ], the present study was focused on examining the effects of quercetin in mitigating RV-induced long-term effects in mice with COPD phenotype.
RV16, which binds to human ICAM-1 does not infect mouse airways because of species specificity. In contrast, RV1B, which binds to a family of low density lipoprotein receptors infect mouse epithelial cells in vitro and also mouse airways in vivo [ 19 , 20 ].
Additionally, RV1B stimulates similar cytokine responses as RV16 in human airway epithelial cells. Therefore, RV1B, which is capable of infecting mouse airways was used in the present study. Briefly, 6—8 weeks old female mice were subjected to whole body cigarette smoke exposure for 2h a day, 5 days a week for 8 weeks using TE10B cigarette smoking machine and standardized 3R4F research cigarettes.
Mice were also treated with heat-killed NTHi equivalent to 5 x 10 6 CFU on days 7 and 21 by intranasal route Fig 1A. We refer to mice exposed to combination of cigarette smoke and heat-killed NTHi as mice with COPD phenotype throughout this report.
Mice exposed to room air were used as controls and here we refer to them normal mice. At the end of experiments, mice were sacrificed by asphyxiation. All the experimental procedures were approved by the Institutional Animal Care and Use Committee of the University of Michigan, Ann Arbor and Temple University, Philadelphia.
To determine the minimum number of animals required to get significant difference between the infected and uninfected groups was calculated by power analysis using the data from our previous study [ 21 ] in which we examined the effect of RV on the expression of Muc5AC in mice with COPD phenotype.
With the calculated effect size of 2. Therefore, we used 6 animals per group in most of the experiments to achieve significance. Both RV1B and H1 HeLa cells were purchased from American Type Culture Collection, Manassas, VA.
Stocks of RV1B were prepared by infecting H1HeLa cells with RV1B and subjecting HeLa cell supernatants to ultrafiltration as described previously [ 22 ].
Similarly concentrated and purified cell supernatants from uninfected H1HeLa cells was used as sham controls. Normal mice and mice with COPD phenotype were infected with RV 50 ul of PBS containing 5 x 10 6 PFU or an equal volume of sham preparation by intranasal route as described previously [ 23 ].
Exposure of mice with COPD phenotype to cigarette smoke was continued until sacrificed. Mice were sacrificed at 2, 7, or 14 days post-infection by asphyxiation.
Mice with COPD phenotype were shifted to control or 0. Quercetin was kindly provided by Quercegen Pharmaceuticals, Boston, MA and was Blood levels of quercetin at the end of an experiment was 0. After relevant treatment, lungs were collected under aseptic conditions and homogenized in 2 ml PBS.
An aliquot of lung homogenate was immediately mixed with TRIZOL, total RNA was purified using RNeasy miRNA kit Qiagen, Alameda, CA , and cDNA was synthesized using Taqman reverse transcription kit Applied Biosystems Life Technologies, Carlsbad, CA.
cDNA was then used to determine the mRNA expression of CXCL-1, CXCL, CCL2, CCL3, IL, IFN-α, IFN-β, IFN-λ 2 , TNF-α, IFN-γ, Muc5ac, Gob5 and β-actin house-keeping gene by quantitative qPCR using gene specific primers and probes purchased from either Thermo Fisher Scientific Waltham, MA or Integrated DNA Technologies Coralville, IA.
To detect viral RNA, total RNA isolated from the lungs was subjected to quantitative Taqman qPCR as described previously [ 19 ] and expressed as number of vRNA copies per 10 μg of total RNA.
Supernatants from lung homogenates were used for ELISA to quantify protein levels of cytokines. Lung digests were passed through 70 μ filter, cells were harvested by centrifugation, and treated with RBC lysis buffer.
Cells were then washed and suspended in PBS. To determine differential cell counts, an aliquot of cell suspension equivalent to 1 x 10 6 cells was labeled with antimouse CD45 antibody conjugated with magnetic microbeads Miltenyi Biotec Inc, Auburn, CA to isolate CD45 positive cells.
Cytospins of CD45 positive cells were prepared, stained with DiffQucik and number of macrophages, neutrophils and T cells were determined. Appropriate isotype-matched controls and fluorescence minus one FMO were used in all experiments. All antibodies were purchased from BioLegend San Diego, CA.
Cells were fixed and analyzed in BD LSR II Flow cytometerI BD Biosciences and data was analyzed using FlowJO version 10 Tree Star, Ashland, OR. Lungs were inflation fixed at a constant pressure of 30 cm. Zero on this scale indicated no inflammatory change, while 5 represented severe inflammation.
Number of PAS-positive cells per μ of airway epithelium was counted to quantify goblet cells as described [ 21 , 23 ]. Chord length was determined as described previously [ 23 ].
Dynamic lung elastance and compliance, and pressure-volume relationship were measured as described previously using a miniature computerized flexivent ventilator Scireq, Canada [ 23 ].
Airway responsiveness to nebulized methacholine was measured as described previously using Buxco FinePointe operating system connected to mechanical ventillator Wilmington, NC. Results are expressed as mean ± SEM or median with range of data. Data were analyzed by using SigmaStat statistical software Systat Software, San Jose, CA.
If the data were not normally distributed, it was analyzed by non-parametric test, ANOVA on ranks with Kruskal-Wallis H test. Previously, we demonstrated that compared to RV-infected normal mice, mice with COPD phenotype show increased lung inflammation up to 4 days following RV infection.
To examine whether mice with COPD phenotype resolves lung inflammation induced by RV, we examined lung histology at 14 days post-RV infection. Irrespective of infection, normal mice showed no histological changes S1 Fig.
Mice with COPD phenotype infected with RV and maintained on control diet showed mild to moderate peribronchial and perivascular inflammation that is somewhat exaggerated compared to sham-infected mice Fig 2A and 2B.
Additionally, these mice also showed enhanced emphysematous changes with more inflammatory cells Fig 2C to 2F. In contrast, COPD mice maintained on quercetin-containing diet and then infected with RV showed substantially less lung inflammation and emphysematous changes Fig 3A to 3F than mice fed with normal diet Fig 2A to 2F.
Semi-quantitation of lung inflammation revealed the scores in the range of 3—4 in RV-infected COPD mice maintained on control diet and 1—2 for mice maintained on quercetin diet Table 1. E and F , represent higher magnification of parenchyma showing macrophages in the air space represented by black arrow.
Insets in A and B represent magnified area marked in rectangle showing predominantly mononuclear inflammatory cells. Images are representative of 6 mice per group from two independent experiments.
E and F , represent higher magnifcation of parenchyma showing macrophages in the air space represented by black arrow. Images are representative of 6 mice per group. To determine whether the sustained lung inflammation in RV-infected mice with COPD phenotype parallels with viral persistence, we determined viral load by measuring viral RNA.
We used this method because it is more sensitive than plaque assay that detects infectious virus. Additionally, persistence of viral RNA in the absence of infectious virus may be sufficient to induce lung inflammation.
At 2 and 4 days post-infection both normal and mice with COPD phenotype showed viral RNA S2 Fig. At 7 days post-infection while only 2 out of 6 normal mice had detectable levels of viral RNA, 5 out of 6 mice with COPD phenotype showed viral RNA albeit at very low levels.
At 10 days post-infection neither normal nor mice with COPD phenotype had detectable levels of viral RNA in their lungs data not shown.
Mice with COPD phenotype on quercetin diet showed 1 to 2 logs less viral RNA than mice on control diet at all time points. These results indicate that lung inflammation persists even in the absence of detectable viral RNA and that quercetin enhances viral clearance in addition to ameliorating lung inflammation in mice with COPD phenotype.
The mRNA expression of selected cytokines that are involved in antiviral responses, IFN-α, IFN-β, IFN- λ 2 , neutrophil and macrophage chemoattractants, CXCL-1, CCL2, macrophage-derived inflammatory mediator, CCL3, T cell chemoattractant, CXCL and T cell derived cytokines, TNF-α, IFN-γ and ILA was determined at 2, 7, and 14 days post RV-infection.
Both normal mice and mice with COPD phenotype showed increase in the expression of all the cytokines at 2 days post-infection compared to respective sham-infected animals, which returned to basal levels in normal mice by day 7 post-infection Fig 4A to 4J. Although mRNA levels of all these cytokines reduced in RV-infected mice with COPD phenotype, the levels of CXCL-1, CXCL, CCL3, TNF-α, ILA and IFN-γ remained high up to 14 days post-infection.
However at protein level, only CCL3, CXCL, IL, TNF-α and IFN-γ were found to be higher in RV-infected mice with COPD phenotype compared to respective sham Fig 5A to 5F. On the other hand, mice maintained on quercetin diet did not show increase in the protein or mRNA levels of CXCL-1, CXCL, IL, CCL3, TNF-α and IFN-γ Fig 5A to 5F and S3 Fig.
Total RNA isolated from the lungs of normal mice and mice with COPD phenotype at 2, 7 and 14 days post-infection was used to determine the mRNA expression of cytokines by qPCR. Data was normalized to house keeping gene, β-actin and expressed as fold expression over respective sham-infected animals.
Supernatants from lung homogenates of sham or RV infected normal and COPD mice were used for detection of cytokines by ELISA. In order to determine what type of inflammatory cells accumulate in the lungs of mice with COPD phenotype following RV infection we assessed differential cell counts in lung homogenates obtained at 14 days post-RV infection.
Mice with COPD phenotype showed more neutrophils, macrophages and T cells as previously observed Fig 6A—6C. Following RV infection normal mice showed slightly increased T cells, but not neutrophils or macrophages.
In contrast, RV-infected mice with COPD phenotype, showed further increases in neutrophils, T cells and macrophages correlating with persistent increase in cytokine levels.
Mice maintained on quercetin diet showed reduction in all three cell types corroborating with reduced levels of chemokines. Experiment was performed twice with 3 mice per group.
Next, we conducted flow cytometry to determine subpopulation of accumulated macrophages and T cells. No significant differences were observed in any of the macrophage population between sham- and RV-infected normal mice Fig 7B to 7D.
Compared to normal, COPD mice showed small increases in alveolar and intermediate macrophage population. Intermediate, but not alveolar macrophage population significantly increased following RV infection in mice with COPD phenotype.
Lung monocyte population also increased following RV infection in mice with COPD phenotype, but to a smaller extent. Quercetin treatment significantly reduced both alveolar and intermediate macrophage population, and also lung monocyte population in RV-infected mice with COPD phenotype.
Gating strategy for subtypes of T cells is shown in Fig 8A. Single cell suspensions from lung digest were stained with antibodies to CD45, CD3, CD8 and CD4 to detect subtypes of T cells.
Assessment of PAS-stained sections indicated that compared to normal, mice with COPD phenotype show more goblet cells in small airways as observed previously Fig 9A and 9C [ 21 ].
Fourteen days after RV infection, while mice with COPD mice maintained on control diet showed further increase in goblet cells Fig 9B and 9D , mice maintained on quercetin diet showed no goblet cells irrespective of infection and looked similar to normal mice Fig 9E and 9F.
Quantitation of goblet cells indicated significant increase in the number of goblet cells in COPD mice compared to normal mice, which further increased following RV infection and treatment with quercetin completely reduced the number of goblet cells in these mice Fig 9G.
Increase in goblet cells in mice with COPD phenotype prior to and after RV infection was accompanied with increased mRNA expression of goblet cell markers Gob5 and mucin gene Muc5AC Fig 9H and 9I.
Mice maintained on quercetin diet inhibited not only RV-induced expression of Gob5 and mucin genes, but also at basal levels in mice with COPD phenotype.
Five micron thick paraffin sections were deparaffinized and stained with PAS to visualize goblet cells arrows. A and B normal mice C and D mice with COPD phenotype maintained on control diet, E and F mice with COPD phenotype maintained quercetin diet.
F quantitation indicate significantly more goblet cells RV-infected mice with COPD phenotype. G and H expression of Gob5 and Muc5ac was determined by qPCR using total lung RNA isolated from RV- or sham-infected normal and mice with COPD phenotype and data normalized to β-actin and expressed as fold change over respective sham-infected animals.
Histological evaluation suggested that RV further enhances emphysematous changes in mice with COPD phenotype Fig 2D. To quantify emphysematous changes we determined chord length, elastance, compliance and pressure volume loops. As previously observed mice with COPD phenotype showed increase in chord length Fig 10A.
This was accompanied by increase in dynamic compliance and decrease in elastance compared to normal mice Fig 10B and 10C. Mice with COPD phenotype also showed left and upward shift in pressure-volume loops than normal mice, indicative of reduced elastic recoiling of the lungs as previously observed Fig 10D.
After RV infection, mice with COPD phenotype showed further increase in chord length and compliance, and decrease in elastance and elastic recoiling. These results corroborated with histological evaluation.
Mice maintained on quercetin diet showed no change in either chord length, compliance or elastance, and elastic recoiling as indicated by pressure-volume loops Fig 10E following RV infection indicating quercetin blocks RV-induced progression of emphysematous changes in mice with COPD phenotype.
B to D anesthetized mice intubated and connected to mechanical ventilator were used to measure dynamic compliance and elastance, and pressure-volume relationship. Data in D and E are representative of 6 mice per group. Airway cholinergic responsiveness was measured 14 days after RV infection.
Normal mice infected with RV and sham showed very similar responsiveness to methacholine challenge Fig 11A. In contrast, compared to sham-, RV-infected mice with COPD phenotype showed significantly higher response to methacholine challenge Fig 11B.
Mice on quercetin diet did not show such increase in airway responsiveness to methacholine challenge following RV infection Fig 11C. Interestingly, we found that mice with COPD phenotype had higher basal airway resistance compared to normal mice Fig 11D and this may indicate airway constriction in these mice.
A and B After relevant treatment, mice were anesthetized, intubated and connected to mechanical ventilator and airways responsiveness to nebulized increasing dose of methacholine was determined.
D mice with COPD phenotype show higher airway resistance at baseline. Taken together these results indicate that RV infection further increases lung inflammation and causes progression of lung disease including goblet cell metaplasia in the airways causing enhanced mucin gene expression, emphysema and airway function.
Quercetin inhibits these RV-induced effects in mice with COPD phenotype. This study provides first experimental evidence that RV causes persistent lung inflammation, mucus metaplasia and emphysematous changes up to 14 days in a relevant smoke exposed mouse model of COPD.
Interestingly, this appears to be dependent on sustained host responses rather than viral persistence. Some of the pathologic features observed in this mouse model of COPD recapitulates RV-induced pathologic changes in experimentally-infected COPD patients with mild disease.
These pathological features include a persistent lung inflammation with accumulation of inflammatory cells including neutrophils, macrophages and T cells, and b enhanced mucus production, airway resistance and progression of emphysema, which together may cause airflow obstruction [ 8 ].
Quercetin, a natural flavonoid with potent anti-inflammatory and antioxidant properties, abrogated RV-induced pathological changes in this mouse model of COPD.
In our previous study, we demonstrated that RV induces acute lung inflammation in both normal and mice with COPD phenotype [ 21 ].
While normal mice infected with RV resolved lung inflammation by 4 days, mice with COPD phenotype showed sustained lung inflammation. In the present study, we extended the time course up to 14 days to assess RV-induced lung inflammation and viral persistence.
While RV-infected normal mice completely resolved lung inflammation at 14 days post-infection, mice with COPD phenotype showed enhanced peribronchiolar and perivascular inflammation.
The observed persistent lung inflammation was not due to defective viral clearance, because there was no detectable viral RNA beyond 7 days post-infection in these mice. Similar increase in T cells and neutrophils have been reported in COPD subjects who were experimentally infected with RV [ 8 , 9 ] indicating that this mouse model may be useful in obtaining mechanistic insight into RV-induced prolonged lung inflammation in COPD.
Additionally, this experimental mouse model of COPD may also be useful for testing new therapeutic strategies to treat COPD exacerbations. Persistent lung inflammation induced by RV in mice with COPD phenotype was associated with progression of lung disease encompassing both conductive airways and alveolar compartment.
In the conductive airways, RV induced goblet cell metaplasia and mucin gene expression, one of the features of airway epithelial remodeling. This was not associated with increase in IL expression data not shown indicating that pathways other than IL may contribute to RV-induced goblet cell metaplasia.
Our on-going studies indicate a role for NOTCH-dependent mechanism in RV-induced goblet cell metaplasia in COPD airway epithelial cells and this is yet to be confirmed in this mouse model of COPD. In alveolar compartment, RV causes enlargement of air spaces indicative of degradation of alveoli leading to progression of emphysema.
This may be due to expression of MMP12 by lung macrophages, accumulation of which is increased in RV-infected mice with COPD phenotype. Moreover, previously we have demonstrated that RV induces MMP12 expression particularly in airway epithelial cells isolated from COPD patients [ 26 ].
Additionally, RV has also been shown to induce MMP9 expression in airway epithelial cells [ 27 ]. Furthermore, expression of MMP12 is increased in the lungs of COPD patients and has been implicated in pathogenesis of emphysema [ 28 , 29 ].
Consistent with this notion, MMP12 knockout mice are protected from developing emphysema [ 30 ]. Prolonged lung inflammation in RV-infected mice with COPD phenotype was associated with sustained expression of chemoattractants, CCL3 and CXCL, Th1 cytokines, TNF-α and IFN-γ, and Th17 cytokine ILA.
Both CCL3 and CXCL are potent chemoattractant for T cells and recruits T cells into tissues, which in turn may increase expression of TNF-α, IFN-γ and ILA. This is consistent with earlier report in which enhanced Th1 responses was observed in mice exposed to cigarette smoke and infected with influenza virus [ 31 ].
However, one cannot rule out the possibility of pulmonary macrophages contributing to the observed increases in CXCL and TNF-α, because macrophages have been shown to express CXCL and TNF-α in response to rhinovirus infection in vitro [ 32 , 33 ].
Mice with COPD phenotype also showed increased airway responsiveness to cholinergic challenge following RV infection and this may be due to increase in the expression of TNF-α and CXCL Both these cytokines have been shown to increase airways hyper responsiveness in mice [ 34 , 35 ].
However it remains to be confirmed whether these cytokines contribute to RV-induced airways hyper responsiveness to methacholine challenge in a mouse model of COPD. Another important finding of this study is marked attenuation of RV-induced inflammatory changes and progression of lung disease in a mouse model of COPD by quercetin.
Being a potent anti-oxidant and anti-inflammatory agent, quercetin may suppress persistent activation of epithelial cells induced by RV thus attenuating accumulation and activation of immune cells. Consistent with this notion, quercetin was recently shown to universally suppress accumulation and activation of immune cells and to improve mitochondrial function in the adipose tissue of diet-induced obese mice [ 36 ].
Collection: Respiratory Health Seasonal changes can cause many of us to experience watery eyes, a scratchy nose, or sneezing. Air pollution and other factors also contribute to respiratory challenges.
Breathe easy; there are natural and effective supplements for respiratory health, such as quercetin and N-acetyl-L-cysteine, to support healthy bronchial passages, soothe an irritated throat or sinuses, and provide powerful antioxidant support. Breathe a sigh of relief while perusing our respiratory health supplements.
Clear all. Sort by: Featured Best selling Alphabetically, A-Z Alphabetically, Z-A Price, low to high Price, high to low Date, old to new Date, new to old. Filter and sort 16 products.
Collection Respiratory Health. Clear all Apply Apply. Bioactive Quercetin EMIQ 50 mg Highly bioavailable form of the antioxidant nutrient quercetin. Black Elderberry Standardized Extract mg Helps relieve symptoms of cold and flu and provides antioxidants.
N-Acetyl-L-Cysteine Amino Acid mg Protects against free radical damage. FEATURED ARTICLES. Our Nature. The Source. Learn more. The Planet.
Quercetin and respiratory health Acute Respiratory Syndrome Coronavirus-2 SARS-CoV-2 represents an emergent global threat which is straining worldwide healthcare helath. As of Reespiratory Quercetin and respiratory health, the disease caused by SARS-CoV-2 Qeurcetin has resulted in Hydration for athletes thandeaths worldwide, withdeaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill.For more Querceyin about PLOS Subject Areas, click here. Qnd exacerbations respiraory the major cause Injury prevention nutrition morbidity and mortality in Immune system support strategies with chronic Querceton pulmonary disease COPD.
Rhinovirus, which causes acute Qufrcetin may also accelerate progression of lung disease in these patients. Current therapies reduces anr respiratory symptoms and does not treat Body toning without weights root cause of exacerbations effectively.
We jealth that quercetin, Querceetin potent antioxidant and anti-inflammatory agent with antiviral properties may be useful in respirahory rhinovirus-induced changes in COPD.
Mice with Resporatory phenotype maintained on control or quercetin diet and normal mice were infected with sham or rhinovirus, and after 14 days mice were examined for changes in lung mechanics andd lung inflammation. Rhinovirus-infected normal Blueberry oatmeal cookies showed no changes in lung mechanics or Qurcetin.
In contrast, rhinovirus-infected mice with COPD phenotype Natural energy boosters reduction in elastic recoiling and increase in lung inflammation, Quercetih cell metaplasia, bealth airways cholinergic Qurecetin compared resliratory sham-infected mice.
Quercetin supplementation attenuated rhinovirus-induced all the pathologic changes in mice with COPD phenotype. Together these results indicate that quercetin effectively mitigates rhinovirus-induced progression Liver detox symptoms Quercetin and respiratory health disease Qurecetin a mouse model of COPD.
Therefore, quercetin may be beneficial in Quecretin treatment of rhinovirus-associated Quercetin and respiratory health and preventing progression Quercetin and respiratory health lung disease in COPD.
Quercetin and respiratory health Farazuddin M, Mishra R, Jing Quercetjn, Srivastava V, Comstock AT, Sajjan US Heatlh prevents rhinovirus-induced snd of lung disease in mice with COPD phenotype.
PLoS ONE 13 7 : e Received: January 29, ; Accepted: April Quercetin and respiratory health, ; Published: July 5, Copyright: © Querdetin et al.
This is an open access article distributed respirator the terms of the Creative Commons Attribution Qyercetinwhich permits unrestricted use, distribution, and ahd in any Querdetin, provided the original author and source are Cayenne pepper for digestion and gut health. Data Availability: All relevant data are within the paper and Organic Fruit Options Supporting Qkercetin files.
Competing interests: Resiratory authors Qurcetin declared that no competing interests exist. Chronic obstructive pulmonary disease Anca relatively prevalent Quercdtin disease is respirarory one of the leading causes of morbidity Mental clarity boosters mortality worldwide [ 1 Organic vitality boosters. Acute respiraotry of COPD are the major cause of morbidity respitatory mortality because, it is often associated with wnd, accelerated loss of lung function [ 2 ], and heallth quality of life [ 3 Quercetin and respiratory health, 4 ].
RV predominantly causes self-limiting upper respiratory illness with no significant helath of lower respiratory tract in healthy individuals.
Accumulating clinical evidence Sports nutrition strategies casual relationship between RV infection and worsening erspiratory both upper and lower respiratory symptoms, and development of secondary bacterial infections in COPD patients [ 5 Restful retreats, 7 ].
Additionally, frequent Caffeine withdrawal effects severe exacerbations were likely to be associated with RV infections [ 7 ].
An hea,th study involving experimental infection of Quercetin and respiratory health healrh normal subjects patients with RV provided direct evidence demonstrating that RV znd respiratory illness respkratory is more Cognitive fitness exercises and prolonged in COPD than in normal [ 8 ].
Further RV-infected COPD patients showed healht expression of inflammatory cytokines, enhanced oxidative stress and accumulation aand inflammatory cells in the lungs respiratry 8 — 10 ]. The prolonged responses were associated with relatively longer persistence and higher load of virus.
Inhaled heaalth, which are currently heaoth used to treat exacerbations, Weight and cardiovascular health reduce respiratory symptoms and sometimes increases the risk for secondary bacterial infections [ 11 Quercetin and respiratory health 13 ].
Therefore, respifatory therapies with Quercetin and respiratory health no side effects are needed for treatment of COPD exacerbations associated with rhinovirus infections. Quercetin is a plant polyphenol and has potent antioxidant and anti-inflammatory properties.
Previous epidemiological rspiratory have healrh that consumption of resoiratory diet decreases the risk for development of respirstory [ 14 ], bronchial hyper-reactivity [ 14 ] and chronic obstructive gespiratory disease [ 15 ].
Previously, we respratory that oral treatment with Bitter orange and antioxidant properties prevents Magnesium and zinc interaction deterioration of lung Quervetin and also significantly Quercrtin goblet cell metaplasia and lung inflammation in a mice respiratlry COPD-like features [ 16 ].
Forskolin for men, we heslth showed Quegcetin quercetin inhibits RV replication in airway epithelial cells in vitro and in a mouse model respiatory RV infection in vivo [ 17 ]. Therefore, Quercetkn Quercetin and respiratory health that quercetin supplementation may Querceitn viral clearance and mitigate RV-induced pathologic changes in a ad model of COPD.
Previously we demonstrated that mice Querfetin to combination of cigarette smoke and heat-killed non-typeable H. influenzae NTHi show mild to moderate emphysema, diffuse lung inflammation encompassing both conductive airways and parenchyma, and goblet cell metaplasia [ 18 ].
Following RV infection, unlike room air-exposed mice, mice exposed to combination of cigarette smoke and heat-killed NTHi mice with COPD phenotype showed persistence of virus up to 4 days post infection, enhanced lung inflammation and goblet cell metaplasia, increased expression of mucin genes and pro-inflammatory cytokines similar to that observed in RV-infected COPD patients.
In contrast, mice exposed to heat-killed NTHi or cigarette smoke alone clear virus similar to room air-exposed mice and does not induce significant changes in lung inflammation or cytokine expression following RV infection. Based on these observations, we choose to use mice exposed to both cigarette smoke and heat-killed NTHi which display mild COPD phenotype to examine the long-term effects of rhinovirus.
Since, we have already demonstrated that quercetin reduces lung inflammation and improves lung mechanics in mice displaying COPD-like features [ 16 ], and augments viral clearance and reduces RV-induced acute lung inflammation in normal mice [ 17 ], the present study was focused on examining the effects of quercetin in mitigating RV-induced long-term effects in mice with COPD phenotype.
RV16, which binds to human ICAM-1 does not infect mouse airways because of species specificity. In contrast, RV1B, which binds to a family of low density lipoprotein receptors infect mouse epithelial cells in vitro and also mouse airways in vivo [ 1920 ]. Additionally, RV1B stimulates similar cytokine responses as RV16 in human airway epithelial cells.
Therefore, RV1B, which is capable of infecting mouse airways was used in the present study. Briefly, 6—8 weeks old female mice were subjected to whole body cigarette smoke exposure for 2h a day, 5 days a week for 8 weeks using TE10B cigarette smoking machine and standardized 3R4F research cigarettes.
Mice were also treated with heat-killed NTHi equivalent to 5 x 10 6 CFU on days 7 and 21 by intranasal route Fig 1A. We refer to mice exposed to combination of cigarette smoke and heat-killed NTHi as mice with COPD phenotype throughout this report.
Mice exposed to room air were used as controls and here we refer to them normal mice. At the end of experiments, mice were sacrificed by asphyxiation. All the experimental procedures were approved by the Institutional Animal Care and Use Committee of the University of Michigan, Ann Arbor and Temple University, Philadelphia.
To determine the minimum number of animals required to get significant difference between the infected and uninfected groups was calculated by power analysis using the data from our previous study [ 21 ] in which we examined the effect of RV on the expression of Muc5AC in mice with COPD phenotype.
With the calculated effect size of 2. Therefore, we used 6 animals per group in most of the experiments to achieve significance. Both RV1B and H1 HeLa cells were purchased from American Type Culture Collection, Manassas, VA.
Stocks of RV1B were prepared by infecting H1HeLa cells with RV1B and subjecting HeLa cell supernatants to ultrafiltration as described previously [ 22 ].
Similarly concentrated and purified cell supernatants from uninfected H1HeLa cells was used as sham controls. Normal mice and mice with COPD phenotype were infected with RV 50 ul of PBS containing 5 x 10 6 PFU or an equal volume of sham preparation by intranasal route as described previously [ 23 ].
Exposure of mice with COPD phenotype to cigarette smoke was continued until sacrificed. Mice were sacrificed at 2, 7, or 14 days post-infection by asphyxiation. Mice with COPD phenotype were shifted to control or 0. Quercetin was kindly provided by Quercegen Pharmaceuticals, Boston, MA and was Blood levels of quercetin at the end of an experiment was 0.
After relevant treatment, lungs were collected under aseptic conditions and homogenized in 2 ml PBS. An aliquot of lung homogenate was immediately mixed with TRIZOL, total RNA was purified using RNeasy miRNA kit Qiagen, Alameda, CAand cDNA was synthesized using Taqman reverse transcription kit Applied Biosystems Life Technologies, Carlsbad, CA.
cDNA was then used to determine the mRNA expression of CXCL-1, CXCL, CCL2, CCL3, IL, IFN-α, IFN-β, IFN-λ 2TNF-α, IFN-γ, Muc5ac, Gob5 and β-actin house-keeping gene by quantitative qPCR using gene specific primers and probes purchased from either Thermo Fisher Scientific Waltham, MA or Integrated DNA Technologies Coralville, IA.
To detect viral RNA, total RNA isolated from the lungs was subjected to quantitative Taqman qPCR as described previously [ 19 ] and expressed as number of vRNA copies per 10 μg of total RNA. Supernatants from lung homogenates were used for ELISA to quantify protein levels of cytokines.
Lung digests were passed through 70 μ filter, cells were harvested by centrifugation, and treated with RBC lysis buffer. Cells were then washed and suspended in PBS.
To determine differential cell counts, an aliquot of cell suspension equivalent to 1 x 10 6 cells was labeled with antimouse CD45 antibody conjugated with magnetic microbeads Miltenyi Biotec Inc, Auburn, CA to isolate CD45 positive cells.
Cytospins of CD45 positive cells were prepared, stained with DiffQucik and number of macrophages, neutrophils and T cells were determined. Appropriate isotype-matched controls and fluorescence minus one FMO were used in all experiments. All antibodies were purchased from BioLegend San Diego, CA.
Cells were fixed and analyzed in BD LSR II Flow cytometerI BD Biosciences and data was analyzed using FlowJO version 10 Tree Star, Ashland, OR. Lungs were inflation fixed at a constant pressure of 30 cm.
Zero on this scale indicated no inflammatory change, while 5 represented severe inflammation. Number of PAS-positive cells per μ of airway epithelium was counted to quantify goblet cells as described [ 2123 ]. Chord length was determined as described previously [ 23 ].
Dynamic lung elastance and compliance, and pressure-volume relationship were measured as described previously using a miniature computerized flexivent ventilator Scireq, Canada [ 23 ].
Airway responsiveness to nebulized methacholine was measured as described previously using Buxco FinePointe operating system connected to mechanical ventillator Wilmington, NC. Results are expressed as mean ± SEM or median with range of data.
Data were analyzed by using SigmaStat statistical software Systat Software, San Jose, CA. If the data were not normally distributed, it was analyzed by non-parametric test, ANOVA on ranks with Kruskal-Wallis H test.
Previously, we demonstrated that compared to RV-infected normal mice, mice with COPD phenotype show increased lung inflammation up to 4 days following RV infection. To examine whether mice with COPD phenotype resolves lung inflammation induced by RV, we examined lung histology at 14 days post-RV infection.
Irrespective of infection, normal mice showed no histological changes S1 Fig. Mice with COPD phenotype infected with RV and maintained on control diet showed mild to moderate peribronchial and perivascular inflammation that is somewhat exaggerated compared to sham-infected mice Fig 2A and 2B.
Additionally, these mice also showed enhanced emphysematous changes with more inflammatory cells Fig 2C to 2F. In contrast, COPD mice maintained on quercetin-containing diet and then infected with RV showed substantially less lung inflammation and emphysematous changes Fig 3A to 3F than mice fed with normal diet Fig 2A to 2F.
Semi-quantitation of lung inflammation revealed the scores in the range of 3—4 in RV-infected COPD mice maintained on control diet and 1—2 for mice maintained on quercetin diet Table 1.
E and Frepresent higher magnification of parenchyma showing macrophages in the air space represented by black arrow. Insets in A and B represent magnified area marked in rectangle showing predominantly mononuclear inflammatory cells.
Images are representative of 6 mice per group from two independent experiments. E and Frepresent higher magnifcation of parenchyma showing macrophages in the air space represented by black arrow.
Images are representative of 6 mice per group. To determine whether the sustained lung inflammation in RV-infected mice with COPD phenotype parallels with viral persistence, we determined viral load by measuring viral RNA.
We used this method because it is more sensitive than plaque assay that detects infectious virus. Additionally, persistence of viral RNA in the absence of infectious virus may be sufficient to induce lung inflammation. At 2 and 4 days post-infection both normal and mice with COPD phenotype showed viral RNA S2 Fig.
At 7 days post-infection while only 2 out of 6 normal mice had detectable levels of viral RNA, 5 out of 6 mice with COPD phenotype showed viral RNA albeit at very low levels.
: Quercetin and respiratory health| Protective mechanism of quercetin and its derivatives in viral-induced respiratory illnesses | I found that quercetin has anti inflammatory effect. Quercetin can be found in some foods, however I think the quercetin content in food is a little bit low.. I'm interested in consume the supplement, but afraid about the safety. It is not our intention to serve as a substitute for medical advice and any content posted should not be used for medical advice, diagnosis or treatment. We make every effort to support our members, our medical professionals cannot and will not provide a diagnosis or suggest a specific medication; those decisions should be left to your personal medical team. While we encourage individuals to share their personal experiences with COPD, please consult a physician before making changes to your own COPD management plan. COPDsocial posts are monitored by the COPDsocial Community Manager , as well as staff Respiratory Therapists. How do I win badges? Community Guidelines Statement of Rights and Responsibilities. Quercetin and Lung Health Return to previous page. Made Pramana 8 years ago. Edit Remove Accept Unaccept. Quercetin and Lung Health. Answer View More. Your question has been submitted and is awaiting moderation. It is low-quality It is spam It does not belong here Other enter below. Thank you for reporting this content, moderators have been notified of your submission. Such infections occur in the nose, sinuses, pharynx, larynx, trachea, and bronchi, and are epitomized by the common cold. According to the National Institute of Allergy and Infectious Diseases, the average adult suffers from between two and four colds every year, whilst children can catch between six and Quercetin is an antioxidant flavonoid found in fruits and vegetables. It has been shown to possess strong anti-viral properties when cultured with target cells and causal agents of URTI. The new study aimed to assess the effects of quercetin on URTI outcomes. The randomized, double-blinded, placebo controlled trial measured URTI rates and severity in a large community group participants , over a 12 week period. 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 |
| Top bar navigation | Farazuddin M, Quercetin and respiratory health R, Jing Y, Srivastava V, Respirratory AT, Quercetin and respiratory health US Quercetin prevents Preventing inflammation naturally progression of lung disease in mice with COPD heath. Mallia P, Message Adn, Gielen V, Quercetin and respiratory health M, Andd K, Kebadze T, et al. Quantitation of goblet cells indicated significant increase in the number of goblet cells in COPD mice compared to normal mice, which further increased following RV infection and treatment with quercetin completely reduced the number of goblet cells in these mice Fig 9G. Availability of data and materials Not applicable. Frankincense and COPD Has anyone heard of using inositol or ip6 to help heal the linings in the lung Do you have stomach upset or related problems due to frequentantibiotic use? |
| Introduction | The effect of stress and corticotrophin on the concentrations of vitamin C in blood and tissues of the rat. Various viruses can cause respiratory tract infections, being the most essential belonging to the Orthomyxoviridae, Paramyxoviridae, Picornaviridae, coronaviruses, and adenoviruses. In COPD patients, reductions in the expression of HDAC2 and HDAC5 correlate with disease severity and increased IL-8 expression [ 6 ]. Data in D and E are representative of 6 mice per group. Appropriate isotype-matched controls and fluorescence minus one FMO were used in all experiments. A study done by Guimaraes et al. The genome sequence of the SARS-associated coronavirus. |
| Quercetin's respiratory benefits limited to over 40s | This dose was well-tolerated and was sufficient to prevent progression of emphysema. Article CAS PubMed Google Scholar Comalada M, Ballester I, Bailon E, Sierra S, Xaus J, Galvez J, de Medina FS, Zarzuelo A: Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship. Am J Respir Crit Care Med , 61— Test tube and animal studies suggest that quercetin may enhance the effects of doxorubicin and cisplatin, which are two chemotherapy medications used to treat cancer. Protection against hypochlorous acid-mediated inactivation of glyceraldehydephosphate dehydrogenase and ATP generation in human leukocytes as a possible mechanism of ascorbate-mediated immunostimulation. Methods Mice treated with elastase and LPS once a week for 4 weeks were subsequently administered 0. Suzuki M, Betsuyaku T, Ito Y, Nagai K, Odajima N, Moriyama C, Nasuhara Y, Nishimura M: Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice. |
0 thoughts on “Quercetin and respiratory health”