Dietary Quercetin Research Articles

Quercetin Protects Mice from ConA-Induced Hepatitis by Inhibiting HMGB1-TLR Expression and Down-Regulating the Nuclear Factor Kappa B Pathway.

The dietary flavonoid quercetin has hepatoprotective effects. We analyzed the effects of quercetin on concanavalin A (ConA)-induced hepatitis in mice and its underlying molecular mechanisms of action. Mice were administered quercetin (50mg/kg body weight, i.p.) or vehicle 30min before intravenous administration of ConA. Quercetin pretreatment significantly reduced the ConA-induced elevations in plasma aminotransferase concentrations and liver necrosis, as well as reducing serum concentrations of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interferon-γ, and interleukin-4. Quercetin pretreatment also reduced expression of high-mobility group box 1 protein (HMGB1) and toll-like receptor (TLR)-2 and TLR-4 messenger RNA (mRNA) and protein in liver tissues. Quercetin pretreatment significantly inhibited degradation of inhibitory kappa B alpha and modulated ConA-induced nuclear translocation in the liver of nuclear factor kappa B (NF-κB) p65. These results demonstrate that quercetin protects against ConA-mediated hepatitis in mice by attenuating the HMGB1-TLRs-NF-κB signaling pathway.

Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress.

Mycotoxins are considered to be significant contaminants of food and animal feed. Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. ZEN has been shown to be cytotoxic, genotoxic, and mutagenic in different cell types. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in ZEN-mediated toxicity in human intestine (HCT116) and kidney (HEK293) cells and evaluated the effects of the two common dietary compounds Quercetin (QUER) and Crocin (CRO). We show that ZEN treatment induces ER stress and activates the unfolded protein response (UPR) as evidenced by XBP1 mRNA splicing and upregulation of GRP78, ATF4, GADD34, PDIA6, and CHOP. Activation of the ER stress response is associated with activation of the mitochondrial pathway of apoptosis. This apoptotic process is characterized by an increase in ROS generation and lipid peroxidation, a loss of mitochondrial transmembrane potential (ΔΨm), and an activation of caspases and DNA damages. We also demonstrate that the antioxidant properties of QUER and CRO help to prevent ER stress and reduce ZEN-induced apoptosis in HCT116 and HEK293 cells. Our results suggest that antioxidant molecule might be helpful to prevent ZEN-induced ER stress and toxicity.

Lipid stability, antioxidant potential and fatty acid composition of broilers breast meat as influenced by quercetin in combination with α-tocopherol enriched diets.

BackgroundDietary supplementation of antioxidants is a vital route to affect the oxidative stability and fatty acid profile of broiler meat. The supplementation of feed with antioxidants decreases degradation of lipids in muscles thereby enhances meat stability.MethodsThe present study was carried out to investigate the influence of dietary quercetin in combination with α-tocopherol on growth performance, antioxidant potential, lipid stability and fatty acid composition in breast meat of birds. Accordingly, one day old 300 Hubbard strain male broiler birds were given three levels of quercetin @100, 200 and 300 mg/kg feed in combination with α-tocopherol @150, 225 and 300 mg/kg feed. The resultant meat was subjected to antioxidant assay, lipid stability, quantification of antioxidants followed by fatty acid profile of broiler breast meat.ResultsThe results explicated that feed treatments imparted momentous effect on gain in weight, and feed conversion efficiency however, intake of feed in birds affected non-momentously. The highest weight gain recorded in T9 as 2374.67 & 2388 g/bird followed by T8 & T6 2350 & 2353.33 and 2293.33 & 2307 g/bird, respectively whilst the lowest in T0 as 1992.67 & 1999 g/bird during the experimental year 2013 and 2014. The results regarding antioxidant potential revealed that among treatments, T9 exhibited highest values for total phenolic contents (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) & ferric reducing antioxidant power assay (FRAP) i.e. 158.70 ± 0.84 mg GAE/100 g, 82.40 ± 0.93 % and 682 ± 2.11 μmol/Fe+2/g, respectively as compared to T0 104.27 ± 1.64 mg GAE/100 g, 54.71 ± 0.64 % and 542.67 ± 1.74 μmol/Fe+2 /g of meat, correspondingly. The TBARS assay indicated that malondialdehydes production in meat increased during storage however, antioxidants deposition varied significantly among treatments. Fatty acid compositional analysis revealed that addition of quercetin with α-tocopherol in the bird’s diet decreased the fatty acid generation particularly saturated fatty acids.ConclusionConclusively, dietary supplementation of quercetin along with α-tocopherol improves growth performance, antioxidant capacity, stability of lipids and fatty acid composition in breast meat of birds.

A Two-Week Quercetin Supplementation in Horses Results in Moderate Accumulation of Plasma Flavonol Concentrations

Quercetin is a plant-derived flavonoid with strong anti-inflammatory properties. Previously, systemic availability of quercetin was documented in horses. We investigated effects of a daily quercetin supplementation on plasma concentrations of quercetin and its metabolites over two weeks. Additionally, plasma concentrations of selected proinflammatory and anti-inflammatory cytokines were analyzed before and immediately after the experiment. Four adult Warmblood horses with a mean body weight ± standard error of the mean of 551 ± 46 kg were used. During a two-week pre-experimental phase and also during the experiment, the use of dietary supplements, apples, or any form of medication was excluded; the horses were offered hay ad libitum, concentrated feed individually (7 AM and PM), and 8 hours access to pasture. During the experiment, quercetin (10 mg/kg body weight) was administrated within the evening meals. Blood samples were collected (jugular vein) three times during the pre-experimental phase and on days 4, 8, 11, and 14 after the start of the experiment. Flavonols in plasma and feed were analyzed by high-performance liquid chromatography; plasma concentrations of cytokines were measured using commercial enzyme-linked immunosorbent assay kits. Daily quercetin supplementations for two weeks increased kaempferol and thus total plasma flavonol concentrations time dependently without accumulation of quercetin or its methylated metabolite isorhamnetin. Although proinflammatory cytokines stayed below detection limit, plasma concentrations of anti-inflammatory cytokines (interleukin-10, interleukin-1 receptor antagonist) were enhanced by quercetin feeding. The study indicates that dietary quercetin supplementation moderately induces total plasma flavonols and thus may be useful in controlling inflammatory disorders in horses. However, anti-inflammatory effects of quercetin must be confirmed in controlled trials.

Risk of prostate cancer in African-American men: Evidence of mixed effects of dietary quercetin by serum vitamin D status.

African-American (AA) men experience higher rates of prostate cancer (PCa) and vitamin D (vitD) deficiency than white men. VitD is promoted for PCa prevention, but there is conflicting data on the association between vitD and PCa. We examined the association between serum vitD and dietary quercetin and their interaction with PCa risk in AA men. Participants included 90 AA men with PCa undergoing treatment at Howard University Hospital (HUH) and 62 controls participating in HUH's free PCa screening program. We measured serum 25-hydroxy vitD [25(OH)D] and used the 98.2 item Block Brief 2000 Food Frequency Questionnaires to measure dietary intake of quercetin and other nutrients. Case and control groups were compared using a two-sample t-test for continuous risk factors and a Fisher exact test for categorical factors. Associations between risk factors and PCa risk were examined via age-adjusted logistic regression models. Interaction effects of dietary quercetin and serum vitD on PCa status were observed. AA men (age 40-70) with normal levels of serum vitD (>30 ng/ml) had a 71% lower risk of PCa compared to AA men with vitD deficiency (OR = 0.29, 95%CI: 0.08-1.03; P = 0.055). In individuals with vitD deficiency, increased dietary quercetin showed a tendency toward lower risk of PCa (OR = 0.91, 95%CI: 0.82-1.00; P = 0.054, age-adjusted) while men with normal vitD were at elevated risk (OR = 1.23, 95%CI: 1.04-1.45). These findings suggest that AA men who are at a higher risk of PCa may benefit more from vitD intake, and supplementation with dietary quercetin may increase the risk of PCa in AA men with normal vitD levels. Further studies with larger populations are needed to better understand the impact of the interaction between sera vitD levels and supplementation with quercetin on PCa in AA men.

Deciphering the Positional Influence of the Hydroxyl Group in the Cinnamoyl Part of 3-Hydroxy Flavonoids for Structural Modification and Their Interaction with the Protonated and B Form of Calf Thymus DNA Using Spectroscopic and Molecular Modeling Studies.

Studies on the interaction of naturally occurring flavonoids with different polymorphic forms of nucleic acid are helpful for understanding the molecular aspects of binding mode and providing direction for the use and design of new efficient therapeutic agents. However, much less information is available on the interactions of these compounds with different polymorphic forms of DNA at the molecular level. In this report we investigated the interaction of two widely abundant dietary flavonoids quercetin (Q) and morin (M) with calf thymus (CT) DNA. Spectrophotometric, spectropolarimetric, viscosity measurement, and molecular docking simulation methods are used as tools to delineate the binding mode and probable location of the flavonoids and their effects on the stability and conformation of DNA. It is observed that in the presence of the protonated form of DNA the dual fluorescence of Q and M resulting from the excited-state intramolecular proton transfer (ESIPT) is modified significantly. Structural analysis showed Q and M binds weakly to the B form (groove binding) compared to the protonated form of CT DNA (electrostatic interaction). In both cases, Q binds strongly to both forms of DNA compared to M.

Inhibition of proteasome activity by the dietary flavonoid Quercetin associated with growth inhibition in cultured breast cancer cells and xenografts

Objective: To study the Inhibition of proteasome activity by the dietary flavonoid Quercetin associated with growth inhibition in cultured breast cancer cells and xenografts. Methods: MCF-7 breast cancer cell cultures and xenografts were treated with quercetin , carried out by following measurement of reduced cellular viability/proliferation, proteasome inhibition, and apoptosis induction. Inhibition of the proteasome was decided by levels of the proteasomal chymotrypsin-like activity, by target proteins, and by accumulation of proteasome target proteins in extracts of the treated cells or tumours. Apoptotic cell inhibition was measured by capase-3/caspase-7 activation, poly (ADP-ribose) polymerase cleavage, and immunohistochemistry for terminal nucleotidyl transferase. Results: This result is carried out for the first time by us that quercetin inhibits the proteasomal chymotrypsin-like activity and induces apoptosis not only in cultured MCF-7 cell lines but also in MCF-7 xenografts moreover, while quercetin has antibreast tumour activity and no toxicity was observed to the tested animals. Conclusion: We have shown that quercetin is an effective proteasome inhibitor in cultured breast cancer cells and in breast cancer xenografts. Furthermore, quercetin induces apoptotic cell death in human breast cancer cells and exhibits anticancer activities in tumours. The results suggest its potential benefits in breast cancer prevention and treatment. Key words: Breast cancer, MCF-7, Proteasome activity, Quercetin , Xenografts.

Quercetin and isorhamnetin aglycones are the main metabolites of dietary quercetin in cerebrospinal fluid.

Reports on the protective effect of certain foods on brain functions are numerous; however, the permeability of the brain barriers by food components is still hardly recognised. There have been in vitro studies aimed at demonstrating this possibility, but not much is known about this phenomenon in in vivo systems. The objective of the study was to determine the metabolites of dietary quercetin (Q) in urine, blood plasma and cerebrospinal fluid (CSF) after intra-rumen administration of Q rich onion dry skin in an animal model. Eleven sheep had permanently implanted cannulas in the third ventricle of the brain as the means for CSF collection. The animals were administered Q at the dose of 10 mg/kg bwt. For 12 h the concentration of Q metabolites was measured in urine, blood plasma, and CSF. It was demonstrated that while in blood plasma Q and isorhamnetin mono-glucuronides or mono-sulphates were the main metabolites (80%), in CSF their aglycones were the dominating ones (88%). Q and IR aglycones are the main Q metabolites present in CSF after dietary Q intake. Their passive transport through blood-CSF barrier or a de-conjugating mechanism within that barrier may be involved.

Effect of chronic dietary quercetin enrichment on cardiac function in dystrophic mice

In Duchenne muscular dystrophy (DMD), cardiac function declines with age and causes 40% of related deaths. New treatments are needed to treat cardiac pathologies related to DMD and preserve cardiac performance across the lifespan. Relative to DMD pathology, consumption of quercetin promotes anti‐inflammatory effects, activates PGC‐1α, up‐regulates endogenous antioxidants, and mitochondrial biogenesis. We investigated chronic 0.2% quercetin dietary enrichment as a strategy to attenuate cardiac function abnormalities in<em style=“mso‐bidi‐font‐style: normal;”> mdx mice. Mdx mice were randomly assigned to: 0.2% quercetin enriched (mdxQ) or control (mdx) diet for 12 months and compared to age matched, control fed C57 mice (n=8/group). Hearts received 7T MRI to quantify cardiac function at 2, 10, and 14 months of age. Reflective of aging, end diastolic volume increased at 14 months in all groups (p=0.001). Quercetin enrichment preserved calculated ejection fraction (p<0.001), stroke volume (p<0.001), fractional shortening (p=0.0013), systolic wall thickness (p=0.006) and cardiac output (p<0.001) at 10 and 14 months in mdxQ compared to mdx. Furthermore, quercetin attenuated increases in end systolic volume at 14 months (p<0.001) in mdx mice. Results confirm age‐dependent declines in cardiac function occur in mdx mice. Data also indicate that chronic quercetin enrichment prevented cardiac dysfunction in mdx mice. Additional experiments are needed to identify physiological mechanisms responsible for protection due to quercetin intake and optimize dosing strategies. Funded by: Duchenne Alliance

Epigenetic Regulation of Pgc1α Splice Variants in Response to Dietary Quercetin Supplementation

Dietary quercetin‐induced increases in Pgc1α occur in a dose‐ and time‐dependent manner and may prevent insulin resistance through an epigenetic mechanism resulting in beneficial mitochondrial adaptations in skeletal muscle. We previously reported that 9 weeks of quercetin supplementation increases skeletal muscle mitochondrial number and whole body insulin sensitivity; however, these effects occurred despite a decrease in Pgc1α. Here, we report on the expression levels of splice variants of Pgc1α and DNA methylation status in muscle of C57BL/J mice fed different diets; low fat (LF), high fat (HF) and high fat + quercetin (HF+Q). Bisulfite conversion with pyrosequencing revealed a higher degree of Pgc1α methylation in HF compared to LF (P < 0.05) and HF+Q (P < 0.05), with the expression of all known splice variants of Pgc1α being decreased (P < 0.05) or unchanged with the exception of N‐truncated Pgc1α (Ntpgc1α) which was increased in LF and HF+Q compared to HF (P < 0.05 and P < 0.01, respectively). The expression of the unique Ntpgc1α splice variant may compensate for decreases in other splice variants, may be epigenetically regulated by DNA methylation and may be the key to attenuation of high fat diet‐induced insulin resistance.

Long‐term Dietary Quercetin Enrichment Improves Muscle Function in Dystrophic Skeletal Muscle

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disease characterized by progressive muscle injury culminating in loss of ambulation and death. It is now clear that increased muscle PGC‐1α pathway activity improves many aspects of disease pathology. Translating this work to human patients necessitates identification of a safe PGC‐1α activator. The purpose of this investigation was to determine the extent to which dietary enrichment of quercetin, a known PGC‐1α activator, improved skeletal muscle function in mdx mice, a model of DMD. mdx mice were maintained on a control or 0.2% quercetin‐enriched diet from two to 14 months of age before sacrifice and tissue collection. Healthy, C57 mice were maintained on a control diet. At 14 months of age body weight was decreased by 12% (p<0.05) in mdx and by 20% in mdxQ (p<0.05 v C57 and mdx) compared to C57. Soleus muscle mass was increased by 35 and 30% (p<0.05) in mdx and mdxQ, respectively, compared to C57. Tetanic force was similar between all groups. Importantly, dietary quercetin enrichment decreased the 42% reduction in specific tension in the mdx soleus compared to C57 by half (p<0.05). In soleus muscle from mdx mice the force produced during the final contraction of a 10 minute fatigue protocol was 8% of the initial force while that of C57 was 16% (p<0.05). Force produced by mdxQ was 12% of initial force though was similar to both groups. In total, these data clearly indicate that long‐term dietary quercetin enrichment provides a benefit to soleus muscle function and should be considered as part of a therapeutic regimen for DMD patients. Supported by the Duchenne Alliance.

사료 내 Quercetin의 첨가가 육계의 생산성, 혈액 생화학 특성, 혈액 내 면역글로불린과 혈액 내 항산화 인자에 미치는 영향

College of Applied Life Science, Jeju National University, 690-756, KoreaABSTRACT This study was conducted to investigate the effects of dietary quercetin on growth performance, blood biochemical parameters, immunoglobulin, and blood antioxidant activity in broiler chickens. Three hundred twenty one-day old Ross broilers were divided 8 treatments (C(), basal diet; C(+), basal diet with antibiotics; vitamin E 20 IU; vitamin E 200 IU; quercetin 20 ppm; quercetin 200 ppm; methoxylated quercetin 20 ppm; methoxylated quercetin 200 ppm) with 4 replicates and 10 birds per replicate. Birds were reared for 35 days and their feed intake and weight gain were measured weekly. At 35d, eight birds of average weight from each replicate were selected for blood collection and analysis. Weight gain of birds in the groups fed quercetin was higher when compare to NC but there was no significant difference. In the serum, creatinine, BUN and AST in quercetin groups significantly decreased compared to those of control (NC and PC) (P<0.05). The contents of IgA and IgM were significantly lower in quercetin groups than those of NC (P<0.05). SOD like activity and MDA content tended to decrease in quercetin groups, however, there was no significant difference among treatments. In conclusion, supplemental quercetin to poultry diet could be positive aspect on performance and blood metabolites. Optimum adding levels was more than 20 ppm.(Key words: quercetin, broiler, blood biochemical parameter, immunoglobulin, blood antioxidant activity)

Health--promoting effect of quercetin in human diet

Quercetin is a plant flavonoid phytochemical exhibiting a broad spectrum of properties i.a. antioxidant, anti-inflammatory and immunomodulatory. However, the effect of quercetin is not clear. This compound at low concentrations can stimulate proliferation of human cells, so it can be a potential drug in the treatment of neurodegenerative diseases and in high concentrations, it induces apoptosis thereby eliminating the infected or abnormal cells and can serve as a potential anticancer drug with wide clinical application. Action of quercetin can be explained by its interference with cellular enzymes, receptors, transporters and signalling system. Due to its widespread occurrence in the plant world, it is an integral component of the human diet. The dietary quercetin occurs most often in the form of β-glycosides connected mostly with rutinose, rhamnose and glucose. Depending on the nutritional habits, the daily intake of flavonoids, including quercetin, ranges from 3 to 70 mg. Epidemiological studies confirm an inverse correlation between the consumption of flavonoids and the incidence of lifestyle diseases and tumor formation. Published data indicate that consumption of foods rich in flavonoids reduces the risk of coronary heart disease. Thus, flavonoids - including quercetin - seem to be an interesting pro-health agent.

Effects of dietary quercetin on female fertility in mice: implication of transglutaminase 2.

Use of the dietary supplement quercetin is on the rise. Because previous studies imply an inhibitory effect of quercetin on male fertility, we explored the effects of this flavonoid on fertility in female mice. Birth outcomes, and ovarian morphology in 4-week-old offspring, were assessed in mice receiving dietary quercetin (5mgkg-1day-1) for 9 months during two breeding periods: from 2 to 6 months (prime reproductive age) and 8 to11 months of age. Quercetin increased birth spacing, leading to a 60% reduction in the number of litters, but enhanced folliculogenesis in ovaries of female offspring. While in young females quercetin caused an almost 70% increase in litter size, in older animals this effect was reversed. Consistent with the inhibitory activity of quercetin on the enzyme transglutaminase 2 (TG2), genetic ablation of TG2 in mice mirrors the effects of quercetin on birth outcomes and follicular development. Further, TG2-null mice lack responsiveness to quercetin ingestion. Our study shows for the first time that dietary quercetin can cause reduced reproductive potential in female mice and implies that TG2 may regulate ovarian ageing.

Anti-tumor potential of nitroxyl derivative Pirolin in the DMBA-induced rat mammary carcinoma model: A comparison with quercetin

BackgroundConsidering the role of oxidative stress in carcinogenesis, we investigated the effect of synthetic antioxidant Pirolin (3-carbamoyl-2,2,5,5-tetramethylpyrroline-1-oxyl) on breast cancer progression. Since the anticancer drugs may cause cardiotoxicity due to oxidative stress in the heart muscle, we also evaluated Pirolin performance in heart tissue and compared its effect with that of the natural dietary flavonoid quercetin. MethodsSprague-Dawley rats were administered with 7,12-dimethylbenz(a)anthracene (DMBA) and then treated ip with an antioxidant (each at a dose of 10mg/kg b.w.) for 14 days. The histopathology of tumors, their size and multiplicity were assesed. The effect of antioxidants on heart tissue was evaluated by the oxidative stress markers and poly (ADP-ribose) polymerase 1 (PARP 1) cleavage. ResultsThe median number of tumors and their volume, at the end of the study, were considerably smaller in both antioxidant-treated groups. We found a better antioxidative performance of quercetin in the heart, since a restoration of the GSH pool and decreased amount of hydroperoxides were observed. Antioxidants did not prevent cardiomyocytes from apoptosis. ConclusionThe attenuation of tumor progression by Pirolin was comparable with the action of quercetin. No negative changes were observed in the heart of animals after Pirolin treatment. Thus, its use in targeting deregulated redox pathways should be further studied.

Quercetin Glycosides-rich Tea Cultivars (&lt;i&gt;Camellia sinensis&lt;/i&gt; L.) in Japan

In an effort to identify tea cultivars with high flavonol content, we measured flavonol glycoside levels in the tea infusions of cultivars in the collection of the National Institute of Vegetable and Tea Science. The cultivars ‘Saemidori’, ‘Sofu’, ‘Surugawase’, ‘Fukumidori’, and ‘Asatsuyu’ among others could be effective sources of quercetin compared to other tea cultivars. Quercetin glycosides in “Saemidori” and “Sofu” remained at a relatively high level (110 – 170 µg/mL aglycone equivalent). These cultivars are indicated as effective sources of dietary quercetin, and are potential sources of quercetin-rich drinks.

In vivo effects of dietary quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria, metabolism, and insulin sensitivity.

Red onions and low doses of the flavonoid, quercetin, increase insulin sensitivity and improve glucose tolerance. We hypothesized that dietary supplementation with red onion extract (RO) would attenuate high fat diet (HFD)-induced obesity and insulin resistance similar to quercetin supplementation by increasing energy expenditure through a mechanism involving skeletal muscle mitochondrial adaptations. To test this hypothesis, C57BL/6J mice were randomized into four groups and fed either a low fat diet (LF), HFD (HF), HFD+quercetin (HF+Q), or HFD+RO (HF+RO) for 9weeks. Food consumption and body weight and composition were measured weekly. Insulin sensitivity was assessed by insulin and glucose tolerance tests. Energy expenditure and physical activity were measured by indirect calorimetry. Skeletal muscle incomplete beta oxidation, mitochondrial number, and mtDNA-encoded gene expression were measured. Quercetin and RO supplementation decreased HFD-induced fat mass accumulation and insulin resistance (measured by insulin tolerance test) and increased energy expenditure; however, only HF+Q showed an increase in physical activity levels. Although quercetin and RO similarly increased skeletal muscle mitochondrial number and decreased incomplete beta oxidation, establishing mitochondrial function similar to that seen in LF, only HF+Q exhibited consistently lower mRNA levels of mtDNA-encoded genes necessary for complexes IV and V compared to LF. Quercetin- and RO-induced improvements in adiposity, insulin resistance, and energy expenditure occur through differential mechanisms, with quercetin-but not RO-induced energy expenditure being related to increases in physical activity. While both treatments improved skeletal muscle mitochondrial number and function, mtDNA-encoded transcript levels suggest that the antiobesogenic, insulin-sensitizing effects of purified quercetin aglycone, and RO may occur through differential mechanisms.

Histological and biochemical outcomes of cardiac pathology in mdx mice with dietary quercetin enrichment.

What is the central question of this study? Does dietary quercetin enrichment improve biochemical and histological outcomes in hearts from mdx mice? What is the main finding and what is its importance? Biochemical and histological findings suggest that chronic quercetin feeding of mdx mice may improve mitochondrial function and attenuate tissue pathology. Patients with Duchenne muscular dystrophy suffer from cardiac pathology, which causes up to 40% of all deaths because of fibrosis and cardiac complications. Quercetin is a flavonol with anti-inflammatory and antioxidant effects and is also an activator of peroxisome proliferator-activated receptor γ coactivator 1α capable of antioxidant upregulation, mitochondrial biogenesis and prevention of cardiac complications. We sought to determine the extent to which dietary quercetin enrichment prevents (experiment 1) and rescues cardiac pathology (experiment 2) in mdx mice. In experiment 1, 3-week-old mdx mice were fed control chow (C3w6m, n = 10) or chow containing 0.2% quercetin for 6 months (Q3w6m, n = 10). In experiment 2, 3-month-old mdx mice were fed control chow (C3m6m, n = 10) or 0.2% chow containing 0.2% quercetin for 6 months (Q3m6m, n = 10). Hearts were excised for histological and biochemical analyses. In experiment 1, Western blot targets for mitochondrial biogenesis (cytochrome c, P = 0.007) and antioxidant expression (superoxide dismutase 2, P = 0.014) increased in Q3w6m mice compared with C3w6m. Histology revealed increased utrophin (P = 0.025) and decreased matrix metalloproteinase 9 abundance (P = 0.040) in Q3w6m mice compared with C3w6m. In experiment 2, relative (P = 0.023) and absolute heart weights (P = 0.020) decreased in Q3m6m mice compared with C3m6m. Indications of damage (Haematoxylin- and Eosin-stained sections, P = 0.007) and Western blot analysis of transforming growth factor β1 (P = 0.009) were decreased in Q3m6m mice. Six months of quercetin feeding increased a mitochondrial biomarker, antioxidant protein and utrophin and decreased matrix metalloproteinase 9 in young mice. Given that these adaptations are associated with attenuated cardiac pathology and damage, the present findings may indicate that dietary quercetin enrichment attenuates dystrophic cardiac pathology, but physiological confirmation is needed.

Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer

Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anti-carcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15–16/group): control (no quercetin), low-dose quercetin (0.02% diet), moderate-dose quercetin (0.2% diet), or high-dose quercetin (2% diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted ‘U’ dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most efficacious and reduced tumor number 20% and tumor volume 78% compared to control mice (C3-Con: 9.0 ± 0.9; C3-0.2%: 7.3 ± 0.9) and (C3-Con: 2061.8 ± 977.0 mm3; and C3-0.2%: 462.9 ± 75.9 mm3). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2%: 1163.2 ± 305.9 mm3; C3-0.02%: 1401.5 ± 555.6 mm3), as was tumor number (C3-2%: 10.7 ± 1.3 mm3; C3-0.02%: 8.1 ± 1.1 mm3). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2% mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment.

A dietary pattern rich in lignans, quercetin and resveratrol decreases the risk of oesophageal cancer.

Dietary lignans, quercetin and resveratrol have oestrogenic properties, and animal studies suggest that they synergistically decrease cancer risk. A protective effect of lignans on the development of oesophageal cancer in humans has recently been demonstrated, and the present study aimed to test whether these three phytochemicals synergistically decrease the risk of oesophageal cancer. Data from a Swedish nationwide population-based case-control study that recruited 181 cases of oesophageal adenocarcinoma (OAC), 158 cases of oesophageal squamous-cell carcinoma (OSCC), 255 cases of gastro-oesophageal junctional adenocarcinoma (JAC) and 806 controls were analysed. Exposure data were collected through face-to-face interviews and questionnaires. The intake of lignans, quercetin and resveratrol was assessed using a sixty-three-item FFQ. Reduced-rank regression was used to assess a dietary pattern, and a simplified dietary pattern score was categorised into quintiles on the basis of the distribution among the control subjects. Unconditional multivariable logistic regression provided OR with 95% CI, adjusted for all the potential risk factors. A dietary pattern rich in lignans, quercetin and resveratrol was mainly characterised by a high intake of tea, wine, lettuce, mixed vegetables, tomatoes, and whole-grain bread and a low intake of milk. There were dose-dependent associations between simplified dietary pattern scores and all types of oesophageal cancer (all P for trend < 0.05). On comparing the highest quintiles with the lowest, the adjusted OR were found to be 0.24 (95% CI 0.12, 0.49) for OAC, 0.31 (95% CI 0.15, 0.65) for OSCC, and 0.49 (95% CI 0.28, 0.84) for JAC. The results of the present study indicate that a dietary pattern characterised by the intake of lignans, quercetin and resveratrol may play a protective role in the development of oesophageal cancer in the Swedish population.