Quercetin Supplementation Research Articles

Restoration of density of interstitial cells of Cajal in the jejunum of diabetic rats after quercetin supplementation.

Interstitial cells of Cajal (ICC) are required for normal motility in the gastrointestinal tract. Depletion of ICC has been associated with diabetic gastroenteropathy. To determine the effect of quercertin supplementation on anoctamin-1 (Ano1) immunoreactive ICC in the myenteric region (ICC-MY) and deep muscular plexus (ICC-DMP) in the jejunum of diabetic rats. Thirty-two 90-day-old male Wistar rats were distributed into the following groups: normoglycemic (C), normoglycemic supplemented with quercetin (CQ; 40 mg daily), diabetic (D), and diabetic supplemented with quercetin (DQ; 40 mg daily). Diabetes was induced by streptozotocin injection. After 120 days, preparations of the jejunal muscular and submucosal layers were immunostained for Ano1 to visualize ICC. Evaluation of the immunofluorescence intensity as well as density of ICC was performed. The density of ICC-MY was 46% lower in group D compared to group C (p < 0.01); ICC-DMP were reduced by 37% (p > 0.05). After quercertin treatment, the densities of ICC-MY were significantly higher in the DQ group compared to group D (ICC-MY: 58%, p < 0.05). Supplementation with quercetin in normoglycemic animals (CQ) compared with group C did not significantly change the ICC density (p > 0.05). In STZ-treated diabetic rats, diabetes promoted a reduction in the density of jejunal ICC-MY with no significant effect on ICC-DMP. Supplementation with quercetin (DQ) appeared to protect ICC-MY from depletion in diabetes possibly due to its antioxidant action.

Protective effect of quercetin on pig intestinal integrity after transport stress is associated with regulation oxidative status and inflammation.

This experiment was conducted to evaluate the effects of quercetin supplementation on intestinal integrity, intestinal reactive oxygen species (ROS) levels and intestinal inflammation in pigs under transport stress. A total of 170 finishing pigs were randomly assigned into two groups. Animals in the control group consumed a basal diet, while those in the treatment group consumed the same diet supplemented with 25 mg quercetin per kg feed. After a 4-week period, pigs were transported for 5 hr. The quercetin-supplemented pigs showed decreased serum levels of endotoxin (P<0.05), increased height of jejunum villi (P<0.05), and increased occludin and zonula occudens-1 (ZO-1) mRNA expression in the jejunum (P<0.05). These parameters are associated with intestinal health and were markedly improved by quercetin supplementation. Pigs consuming the quercetin-supplemented diet had lower intestinal levels of ROS and malondialdehyde (MDA) compared with the control group (P<0.05). This finding coincided with greater inhibition of the innate immune system (P<0.05), including mitogen-activated protein kinase (MAPK), protein kinase B (Akt) and nuclear factor κB (NF-κB) signaling pathways, as well as decreased expression of inflammatory cytokines in the jejunum. These results indicate that quercetin alleviates intestinal injury in pigs during transport, probably through modulation of intestinal oxidative status and inflammation.

Insight to drug delivery aspects for colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide in human beings. Surgery, chemotherapy, radiotherapy and targeted therapies are the conventional four approaches which are currently used for the treatment of CRC. The site specific delivery of chemotherapeutics to their site of action would increase effectiveness with reducing side effects. Targeted oral drug delivery systems based on polysaccharides are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific drug delivery to colon increases its concentration at the target site, and thus requires a lower dose and hence abridged side effects. Some novel therapies are also briefly discussed in article such as receptor (epidermal growth factor receptor, folate receptor, wheat germ agglutinin, VEGF receptor, hyaluronic acid receptor) based targeting therapy; colon targeted proapoptotic anticancer drug delivery system, gene therapy. Even though good treatment options are available for CRC, the ultimate therapeutic approach is to avert the incidence of CRC. It was also found that CRCs could be prevented by diet and nutrition such as calcium, vitamin D, curcumin, quercetin and fish oil supplements. Immunotherapy and vaccination are used nowadays which are showing better results against CRC.

Hepatotoxicity and Nephrotoxicity in Mice Induced by Abamectin and Ameliorating Effect of Quercetin

Abamectin is a natural fermentation product and widely used as insecticide, acaricide and anthelmintic drug. This study was conducted to investigate the acute toxicity of abamectin toward male mice and evaluate the impact effect of repeated sublethal dose (1/10 LD 50 for 14 days) on some hematological, immunological and biochemical parameters as well as histopathological changes. Also, the effectiveness of quercetin in alleviating the toxicity of abamectin was investigated. The data indicated that, there was significant decrease in the body weight gain and increase in the relative weights of liver and kidney of animals treated with abamectin compared with control. Also, a significant decline in hemoglobin content (Hb), packed cell volume (PCV) and red blood cells (RBC), while the white blood cells (WBC), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) increased. Abamectin reduced the cellular immunity; active and total rosette-forming cells (RFC) and humoral immunity; plaque forming cells (PFC) and serum immunoglobulins; total Ig, IgG and IgM levels. Oxidative stress of abamectin was assessed by significant increase of lipid peroxidation (LPO), glutathione peroxidase (GPx) activity and decrease of glutathione content (GSH). Also, the function parameters of liver; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) activities and kidney; creatinine and urea concentrations were significantly increased by abamectin treatment. The above findings were confirmed by histopathological examination of liver and kidney. In addition, the results showed that quercetin supplementation significantly protected the adverse effects of abamectin.

Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats

Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography–based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and cholesterol efflux.

Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats

In this study, the protective effect of quercetin was evaluated against arsenic induced reproductive ailments in male rats. For this purpose, male rats (n = 5/group) weighing 180–250 g were used. First group served as control, second group received arsenic (50 ppm) in drinking water. Third group was treated with quercetin (50 mg/kg) alone, while fourth group received arsenic + quercetin. All treatments were carried out for 49 days. After treatment, animals were killed by decapitation; testis and epididymis were dissected out. Right epididymis was minced immediately for comet assay, while left epididymis was processed for histology. Similarly, right testis was homogenized for estimation of daily sperm production (DSP) and detection of metal concentration. The results of our research revealed that arsenic treatment did not cause any significant change in body weight and testicular volume. Quercetin treatment significantly prevented tissue deposition of arsenic within the testis. Arsenic treatment caused a significant reduction in DSP, however, in the arsenic + quercetin-treated group and quercetin alone-treated group, DSP was significantly high as compared to the arsenic-treated group. Histological study of epididymis showed empty lumen in arsenic-treated group while in arsenic + quercetin-treated group and quercetin alone-treated group, lumen were filled with sperm and were comparable to control. Sperm DNA damage, induced by arsenic, was significantly reversed toward control levels by supplementation of quercetin. These results suggest that quercetin not only prevents deposition of arsenic in tissues, but can also protect the sperm DNA damage.

The Effects of Oral Quercetin Supplementation on Splanchnic Glucose Metabolism in 1-Week-Old Calves Depend on Diet after Birth1–3

Background: Inadequate colostrum supply results in insufficient intake of macronutrients and bioactive factors, thereby impairing gastrointestinal development and the maturation of glucose metabolism in neonatal calves. The flavonoid quercetin has been shown to have health-promoting properties, including effects in diabetic animals. However, quercetin interacts with intestinal glucose absorption and might therefore exert negative effects in neonates.Objective: We evaluated the interaction between neonatal diet and quercetin feeding on splanchnic glucose metabolism in neonatal calves.Methods: Calves (n = 28) were assigned to 4 groups and fed either colostrum or a milk-based formula on days 1 and 2 and supplemented daily with 148 μmol quercetin aglycone/kg body weight [colostrum with quercetin (CQ+)/formula with quercetin (FQ+)] or without this substance [colostrum without quercetin (CQ−)/formula with quercetin (FQ−)] from days 2–8. From day 3 onward, all calves received milk replacer. A xylose absorption test was performed on day 3, and on day 7, blood samples were collected to study glucose first-pass uptake after [13C6]-glucose feeding and intravenous [6,6-2H2]-glucose bolus injection. Plasma concentrations of metabolites and hormones were measured by taking additional blood samples. A biopsy specimen of the liver was harvested on day 8 to measure the mRNA expression of gluconeogenic enzymes.Results: Higher postprandial plasma concentrations of glucose, lactate, urea, adrenaline, noradrenaline, insulin, and glucagon on day 7 in colostrum-fed calves indicate that metabolic processes were stimulated. Postabsorptive xylose and glucose plasma concentrations each increased by an additional 26%, and splanchnic glucose turnover decreased by 35% in colostrum-fed calves, suggesting improved glucose absorption and lower splanchnic glucose utilization in colostrum-fed calves. Quercetin supplementation resulted in higher noradrenaline concentrations and enhanced peak absorption and oxidation of [13C6]-glucose by 10%. Liver mitochondrial phosphoenolpyruvate carboxykinase mRNA abundance was reduced by 34% in colostrum-deprived calves.Conclusions: Feeding colostrum during the first 2 d of life is crucial for maturation of splanchnic glucose metabolism in calves. Supplementing quercetin improves gastrointestinal absorption capacity, particularly in colostrum-deprived calves.

The effect of quercetin on cyclosporine-A-induced cardiotoxicity in adult male albino rats

Background Cyclosporine-A (Cs-A) is the most widely used immunosuppressive agent in organ transplantation and autoimmune disease treatment. Nevertheless, its therapeutic use is associated with serious effects, including cardiotoxicity. Quercetin is one of the naturally occurring flavonoids present in a lot of the human diets. Objective The aim of this study was to evaluate the effect of quercetin on cyclosporine-induced cardiotoxicity in adult male albino rats. Materials and methods Forty adult male rats were included and divided into four groups (10 rats each): group I was the control group; group II (the quercetin group) rats received daily intraperitoneal injection of quercetin (15 mg/kg body weight/day) for 4 weeks; group III (the cyclosporine group) rats received daily subcutaneous injection of Cs-A (20 mg/kg body weight/day) for 4 weeks; and group IV (the cyclosporine and quercetin group) rats received Cs-A and quercetin for 4 weeks. Heart specimens were taken and processed for light microscopy study (H&E and Masson’s trichrome staining and immunohistochemical staining for caspase-3) and electron microscopy study. Results Group III showed prominent myocardial fiber degeneration with areas of myofibril loss and interstitial hemorrhage. This was supported by the positive reaction for apoptotic marker caspase-3. An increase in the collagen fibers in the endomysium was obvious. Electron microscopic results showed irregular nucleus with disruption of the sarcolemma and intercalated discs. The cytoplasm showed an area of myofibril loss and mitochondrial swelling. Group IV showed improvement in most light and electron microscope changes described before. Conclusion Quercetin can be a natural cardioprotective agent and can be used to improve cyclosporine-induced cardiotoxicity, as it has antioxidant and anti-inflammatory enzyme activities. We advise taking a diet rich in quercetin or dietary supplementation.

Supplementation of the Pure Flavonoids Epicatechin and Quercetin Affects Some Biomarkers of Endothelial Dysfunction and Inflammation in (Pre)Hypertensive Adults: A Randomized Double-Blind, Placebo-Controlled, Crossover Trial ,

Background: Consumption of flavonoid-rich foods such as cocoa and tea may reduce cardiovascular disease risk. The flavonoids epicatechin (in cocoa and tea) and quercetin (in tea) probably play a role by reducing endothelial dysfunction and inflammation, 2 main determinants of atherosclerosis.Objective: We studied the effects of supplementation of pure epicatechin and quercetin on biomarkers of endothelial dysfunction and inflammation.Methods: Thirty-seven apparently healthy (pre)hypertensive men and women (40–80 y) participated in a randomized, double-blind, placebo-controlled crossover trial. Participants ingested (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for a period of 4 wk, in random order. Plasma biomarkers of endothelial dysfunction and inflammation were measured at the start and end of each 4-wk intervention period. The differences in changes over time between the intervention and placebo periods (Δintervention − Δplacebo) were calculated and tested with a linear mixed model for repeated measures.Results: Epicatechin changed Δepicatechin − Δplacebo for soluble endothelial selectin (sE-selectin) by −7.7 ng/mL (95% CI: −14.5, −0.83; P = 0.03) but did not significantly change this difference (−0.30; 95% CI: −0.61, 0.01; P = 0.06) for the z score for endothelial dysfunction. Quercetin changed Δquercetin − Δplacebo for sE-selectin by −7.4 ng/mL (95% CI: −14.3, −0.56; P = 0.03), that for IL-1β by −0.23 pg/mL (95% CI: −0.40, −0.06; P = 0.009), and that for the z score for inflammation by −0.33 (95% CI: −0.60, −0.05; P = 0.02).Conclusions: In (pre)hypertensive men and women, epicatechin may contribute to the cardioprotective effects of cocoa and tea through improvements in endothelial function. Quercetin may contribute to the cardioprotective effects of tea possibly by improving endothelial function and reducing inflammation. This trial was registered at clinicaltrials.gov as NCT01691404.

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.

Quercetin supplementation does not enhance cerebellar mitochondrial biogenesis and oxidative status in exercised rats

The present study tested the hypothesis that quercetin may inhibit the mitochondrial and antioxidant adaptations induced by exercise in cerebellar tissue. Thirty-five 6-week-old Wistar rats were randomly allocated into the following groups: quercetin, exercised (Q-Ex; n = 9); quercetin, sedentary (Q-Sed; n = 9); no quercetin, exercised (NQ-Ex; n = 9); and no quercetin, sedentary (NQ-Sed; n = 8). After 6 weeks of quercetin supplementation and/or exercise training, cerebellums were collected. Protein carbonyl content (PCC), sirtuin 1, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), messenger RNA levels, citrate synthase (CS), and mitochondrial DNA were measured. When Q-Sed was compared with NQ-Sed, PCC (P < .005) showed decreased levels, whereas PGC-1α, sirtuin 1 (both, P < .01), mitochondrial DNA (P < .001), and CS (P < .01) increased. However, when Q-Ex was compared with Q-Sed, PCC showed increased levels (P < .001), whereas CS decreased (P < .01). Furthermore, the NQ-Ex group experienced an increase in PGC-1α messenger RNA levels in comparison with NQ-Sed (P > .01). This effect, however, did not appear in Q-Ex (P < .05). Therefore, we must hypothesize that either the dose (25 mg/kg) or the length of the quercetin supplementation period that was used in the present study (or perhaps both) may impair exercise-induced adaptations in cerebellar tissue.

Dose-dependent induction of signaling pathways by the flavonoid quercetin in human primary hepatocytes: A transcriptomic study.

Quercetin is widespread in plant kingdom and consumed regularly with human diet (16 mg/day). Due to reported positive effects on health, quercetin supplements with recommended doses up to 2 g/day are offered. However, molecular effects of such high doses on human liver have not been assessed yet. Therefore, molecular effects on human hepatocytes were analyzed to help assessing the risk of quercetin supplementation. Molecular effects of three different quercetin concentrations on gene expression in human hepatocytes were investigated by microarray analysis. Possible new signaling pathways were investigated using reporter gene assays. Quercetin concentrations representing the normal intake showed weak effects on mRNA expression in liver cells. In contrast, supplemental doses affect immune response and p53 signaling and might be associated with cancer. Additionally, quercetin showed inhibition of transcriptional activation and mRNA-expression of HNF4α and its target genes. Inhibitory effects were also found for FXR, LXRα, and PXR. Normal intake of quercetin seems to play a minor regulatory role, while supplement doses may have great effects on gene expression in hepatocytes. However, since it is not clarified whether such high doses of quercetin exert positive or negative effects, a careful handling of quercetin supplements is advised.

Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial

Prospective cohort studies showed inverse associations between the intake of flavonoid-rich foods (cocoa and tea) and cardiovascular disease (CVD). Intervention studies showed protective effects on intermediate markers of CVD. This may be due to the protective effects of the flavonoids epicatechin (in cocoa and tea) and quercetin (in tea). We investigated the effects of supplementation of pure epicatechin and quercetin on vascular function and cardiometabolic health. Thirty-seven apparently healthy men and women aged 40-80 y with a systolic blood pressure (BP) between 125 and 160 mm Hg at screening were enrolled in a randomized, double-blind, placebo-controlled, crossover trial. CVD risk factors were measured before and after 4 wk of daily flavonoid supplementation. Participants received (-)-epicatechin (100 mg/d), quercetin-3-glucoside (160 mg/d), or placebo capsules for 4 wk in random order. The primary outcome was the change in flow-mediated dilation from pre- to postintervention. Secondary outcomes included other markers of CVD risk and vascular function. Epicatechin supplementation did not change flow-mediated dilation significantly (1.1% absolute; 95% CI: -0.1%, 2.3%; P = 0.07). Epicatechin supplementation improved fasting plasma insulin (Δ insulin: -1.46 mU/L; 95% CI: -2.74, -0.18 mU/L; P = 0.03) and insulin resistance (Δ homeostasis model assessment of insulin resistance: -0.38; 95% CI: -0.74, -0.01; P = 0.04) and had no effect on fasting plasma glucose. Epicatechin did not change BP (office BP and 24-h ambulatory BP), arterial stiffness, nitric oxide, endothelin 1, or blood lipid profile. Quercetin-3-glucoside supplementation had no effect on flow-mediated dilation, insulin resistance, or other CVD risk factors. Our results suggest that epicatechin may in part contribute to the cardioprotective effects of cocoa and tea by improving insulin resistance. It is unlikely that quercetin plays an important role in the cardioprotective effects of tea. This study was registered at clinicaltrials.gov as NCT01691404.

Effects of quercetin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials

ABSTRACTBackground: In spite of promising experimental findings, randomized controlled trials (RCTs) have yielded mixed results on the impact of quercetin supplementation on plasma lipid levels.Aim: The present study aimed to quantify the effects of quercetin on plasma lipids using a meta-analysis of RCTs.Methods: A systematic literature search of Medline was conducted for RCTs that investigated the efficacy of quercetin supplementation on plasma lipids comprising total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in lipid concentrations using a random-effects model. Meta-regression analysis was conducted to assess the effect of quercetin dose and duration of supplementation as moderators on the calculated effect measures.Results: Five RCTs totaling 442 subjects (221 in the quercetin and 221 in the control group) fulfilled the eligibility criteria and selected for analyses. Combined estimate of effect size for the impact of quercetin on plasma LDL-C (WMD: 1.43 mg/dL, 95% CI: −0.92–3.78, p = 0.23), HDL-C (WMD: 0.26 mg/dL, 95% CI: −0.74–1.25, p = 0.61) and triglycerides (WMD: −9.42 mg/dL, 95% CI: −27.80–8.96, p = 0.32) was not statistically significant. However, a borderline significant but clinically non-relevant increase in total cholesterol was observed (WMD: 3.13 mg/dL, 95% CI: −0.01–6.27, p = 0.05). When the analysis was confined to the subgroups of studies with quercetin doses ≥500 mg/day and follow-up of ≥ 4 weeks, a significant increase in total cholesterol (WMD: 3.57 mg/dL, 95% CI: 0.21–6.92, p = 0.04) and a decline in triglycerides (WMD: −24.54 mg/dL, 95% CI: −33.09 to −15.99, p < 0.00001) was observed, but LDL-C and HDL-C concentrations remained unchanged (p > 0.05). Changes in plasma triglycerides, but not other indices of lipid profile, were significantly associated with quercetin dose (slope: −0.057; 95% CI: −0.103 to −0.010; p = 0.02) and duration of supplementation (slope: −5.314; 95% CI: −9.482 to −1.147; p = 0.01).Conclusion: Available evidence from RCTs does not suggest any clinically relevant effect of quercetin supplementation on plasma lipids, apart from a significant reduction of triglycerides at doses above 50 mg/day.

Strenuous exercise and quercetin intake stimulates aortic NFkB signaling

NF‐kB belongs to a family of structurally related inducible transcription factors known to be activated in the vessel wall in atherosclerosis and other diseases NF‐kB activation is mediated by diverse extracellular signals including oxidized LDL, and inflammatory cytokines. In the current study we combined quercetin and exercise to examine the effect of the combination.Study Design and MethodsWe investigated the combination of exercise and quercetin intake in C57BL6 normal male mice fed normal mouse chow. Mice were divided into four groups. These groups are as follows: Control mice, left untreated; control quercetin group, orally supplied with 100 μg/day of quercetin without exercising; exercise group without quercetin, and exercise group with quercetin supplements. The exercise groups were run on a treadmill for 30 minutes, 30m/m/ 5 days/week for 60 days. At the end of the study, mice were sacrificed tissues such as the aorta, adipose and livers were collected for gene expressions for genes associated with NFkB signaling, inflammation, and lipoprotein metabolism were analyze.Results and DiscussionNFkB mRNA levels was significantly (P&lt;0.05) upregulated with the combination of exercise and quercetin intake, however on the other hand exercise or quercetin intake alone have resulted in significant (P&lt;0.05) down regulation of its mRNA levels.ConclusionThis study demonstrated that quercetin intake with exercise modulate NFkB signaling and its associated genes.

Effects of Quercetin on Muscle Function during IL‐6‐induced Cancer Cachexia

Cachexia is a devastating wasting condition that occurs secondary to chronic diseases including AIDS, COPD, and cancer. Characterized by a loss of body weight including adipose tissue and muscle atrophy, 20-50% of cancer patients are affected with an annual mortality rate of 80%. It is known that IL-6 drives cachexia in the male ApcMin/+ mouse. Quercetin, an anti-inflammatory flavonoid, has been shown to attenuate symptoms of cachexia. There is evidence that this occurs through the IL-6 pathway; however, this has not been directly tested. The purpose of this study was to determine whether quercetin could attenuate muscle function loss caused by systemic IL-6 over-expression in female ApcMin/+mice. Our hypothesis was that IL-6 over-expression would exacerbate muscle strength and endurance decrements, which would be attenuated by quercetin supplementation in cachectic female ApcMin/+ mice. Female ApcMin/+ mice (n=24) were divided into 4 groups at 15 weeks of age: 1) Control 2) IL-6 electroporation (50 μg plasmid in 50 μl PBS), 3) daily quercetin gavage (75 mg/kg body weight), 4) IL-6 electroporation + quercetin. Functional testing including voluntary grip strength, run to fatigue, and DEXA scan were performed before treatment and at time of sacrifice. Quercetin attenuated grip strength loss compared to control mice (p=0.02); however, this effect was abolished by the overexpression of IL-6 in addition to quercetin. Quercetin was unable to rescue muscle endurance loss. Further analysis will determine the pathways by which quercetin and IL-6 exert their effects on muscular strength and endurance in cachectic female ApcMin/+mice.

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 &lt; 0.05) and HF+Q (P &lt; 0.05), with the expression of all known splice variants of Pgc1α being decreased (P &lt; 0.05) or unchanged with the exception of N‐truncated Pgc1α (Ntpgc1α) which was increased in LF and HF+Q compared to HF (P &lt; 0.05 and P &lt; 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.

Effect of long term quercetin supplementation on dystrophic cardiac pathology in mdx/utrn+/‐mice

Duchenne muscular dystrophy (DMD) causes cardiac dysfunction and up to 40% of deaths are attributable to cardiac pathologies. Novel interventions are needed to counter cardiac complications. Recent findings indicate that increased PGC‐1α activity increases utrophin expression, among other benefits, and attenuates disease pathology in dystrophic skeletal muscle. We tested the hypothesis that, quercetin, a SIRT‐1/PGC‐1α activator, would also protect cardiac muscle and alleviate cardiac performance complications in a mouse DMD model. Mdx/utrn+/‐ mice were randomly assigned to standard chow or a 0.2% quercetin enriched diets from 2‐10 months (n=8/group). Age matched C57 mice were fed a control diet. Hearts received 7T MRI to quantify cardiac function at 2 and 10 months of age. Findings confirmed that as compared to C57, mdx/utrn+/‐ mice exhibited diminished cardiac function in a time‐dependent fashion in that end diastolic volume increased at 10 months in both mdx/utrn+/‐ groups (p=0.001). Quercetin enrichment preserved ejection fraction (p&lt;0.001), systolic wall thickness (p=0.006), and fractional shortening (p&lt;0.001) at 10 months of age in mdx/utrn+/‐ mice compared to mdx/utrn+/‐ control fed mice. Quercetin enrichment attenuated increased end systolic volume at 10 months (p&lt;0.001) in mdx/utrn+/‐ quercetin fed mice versus control‐fed mdx/utrn+/‐ mice. Data indicate that quercetin enrichment prevents the age‐dependent cardiac function decline in mdx/utrn+/‐ mice. Additional research should identify the underlying mechanisms and refine quercetin dosing strategies. Funded by Duchenne Alliance.

Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats

Diet-induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability, and when they reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans-resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high-fat sucrose diet (HFS) and, in turn, improve gut health. Wistar rats were randomised into four groups fed an HFS diet supplemented or not with trans-resveratrol [15 mg/kg body weight (BW)/day], quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans-resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS-diet-induced gut microbiota dysbiosis. In contrast, trans-resveratrol supplementation alone or in combination with quercetin scarcely modified the profile of gut bacteria but acted at the intestinal level, altering the mRNA expression of tight-junction proteins and inflammation-associated genes.