Quercetin Supplementation Research Articles

PSIV-8 The Effects of Quercetin Supplementation During Oocyte Maturation on the in Vitro Production of Pig Embryos

Abstract Oocyte viability can be reduced during in vitro maturation due to oxidative stress and a lack of antioxidant presence in the environment. Additionally, oxidative stress is a culprit in the relatively low success rate of in vitro fertilization (IVF) in pigs. Quercetin is a natural antioxidant dietary flavonoid that has the ability to suppress free radical formation. The purpose of this study was to determine the effects of the quercetin supplementation during oocyte maturation on IVF embryonic development success rates in pigs. Oocytes were matured for 40 to 44 h supplemented with quercetin (0, 0.25, 0.5, 0.75 mM; Sigma-Aldrich Co.) then fertilized using frozen-thawed boar semen (1.0 x 105 sperm cells/mL) and co-incubated for 6-8 h followed by embryo culture for 144 h. After maturation, oocytes were evaluated for cumulus cell expansion (n = 300, r = 6) under a stereomicroscope (scale 0 to 4) then denuded to determine reactive oxygen species (ROS) production (n = 135) by measuring the fluorescent intensity from the oxidation of 2’,7’-dichlorodihydrofluorescein diacetate. After IVF, zygotes were fixed, permeabilized, and stained with bisBenzimide H 33342 trihydrochloride and evaluated for penetration, polyspermy, and pronucleus formation rates (n = 480) and embryos were evaluated for cleavage and blastocyst formation (n = 599) at 48 h and 144 h post-IVF, respectively. Cumulus cell expansion score percentages were determined and analyzed using the Chi-squared test. Fluorescent intensities of oocytes were analyzed using a GLM and compared using LSD after adjusting the control group value to 1. The IVF and embryo development data were reported as the percent observed/drop and mean percentages, and were analyzed using GLM. Means were analyzed using Tukey’s test. The average cumulus cell expansion post-maturation when no quercetin was supplemented was 2.78 ± 0.15. As quercetin supplementation increased, cumulus cell expansion decreased (1.33 ± 0.11 for 0.75 mM quercetin). Supplementation of 0.25 mM quercetin decreased (P < 0.05) ROS levels (0.52 ± 0.12) but 0.75 mM quercetin increased (P < 0.05) ROS levels (1.73 ± 0.11) compared with no quercetin. Supplementation of quercetin decreased (P < 0.05) oocyte penetration rates, increased (P < 0.05) polyspermic oocytes and pronuclear formation. Quercetin supplementation during maturation also reduced embryonic development success through decrease (P < 0.05) of cleavage and blastocyst formation rates compared with no quercetin (78.69 ± 0.02 and 31.18 ± 0.03, respectively). It appears that quercetin supplementation to the oocyte maturation media in concentrations greater than 0.25 mM are detrimental during in vitro production of pig embryos. Supplementation of 0.25 mM quercetin appears to not be different to supplementing quercetin to the maturation media except for reduction in ROS concentrations in the oocyte.

Effect of crocin and quercetin supplementation in cryopreservation medium on post-thaw human sperm quality.

Biochemical and physical changes during the cryopreservation process adversely affect sperm function required for fertilization. Recently, many studies have been conducted to find effective pre-freezing treatments to limit these damages. The present study aimed to investigate the effects of pre-freezing treatment with quercetin and crocin, individually or in combination, on sperm parameters after thawing procedure. For this, semen samples from 20 normozoospermic men were collected and then each sample was divided into five equal parts: 1. fresh group 2. frozen-thawed group without addition of antioxidants 3. frozen-thawed group containing 1 mM crocin, 4. frozen-thawed group containing 50 μM quercetin, and 5. frozen-thawed group containing a combination of 1 mM crocin and 50 μM quercetin. Pre-cryopreservation and post-thaw sperm motility, morphology, viability, DNA fragmentation, reactive oxygen species [1] (ROS) levels, and mitochondrial membrane potential [2] (MMP) were investigated. Cryopreservation significantly reduced sperm quality. Both crocin and quercetin individually improved sperm progressive motility, decreased ROS levels, reduced DNA fragmentation, and marginally increased MMP, though crocin seems to be more successful in protecting sperm quality. More interestingly, the combined addition of crocin and quercetin to the sperm-freezing medium did not show positive effects on sperm quality. Crocin and quercetin may play a role in mitigating the cryopreservation-induced injury to sperm.

The effect of high-intensity interval training and quercetin nanoliposome consumption on angiogenesis indexes in the heart tissue of myocardial infarction rats

Background: Myocardial infarction is the death of the heart muscle tissue that causes tissue damage and inflammation. Quercetin consumption and interval training can probably prevent the progression of this condition in the active parts of the myocardium by activating angiogenesis pathways and stimulating hypoxia factor-1a (HIF-1a) at the onset of infarction. Objectives: This study investigates the effect of high-intensity interval training and quercetin nanoliposome consumption on angiogenesis indexes in the heart tissue of myocardial infarction rats. Methods: In this experimental study, 30 male rats weighing 250 ± 20 g were randomly divided into five groups including: 1) myocardial infarction + training, 2) myocardial infarction + supplement, 3) myocardial infarction + training + supplement, 4) healthy control, and 5) myocardial infarction. Myocardial infarction was induced by subcutaneous injection of soprenaline hydrochloride at a dose of 80 mg / kg. Groups 2 and 3 received quercetin daily at a dose of 0.25 mg / kg body weight by gavage. Groups 1 and 3 performed 5 sessions of training protocol per week for 8 weeks. The Smirnov-Kolmogorov, one-way analysis of variance and Tukey’s post hoc test were used to analyze the data and the alpha level less than 0.05 was considered as a significant level. Results: Interval training and quercetin supplementation had a significant effect on increasing VEGF and HIF-1a gene expression (P=0.0009). Conclusion: The combined effect of interval training and quercetin consumption may prevent the progression of myocardial infarction by activating angiogenesis factors VEGF and HIF-1a in the early stages, and may play an effective role in preventing this disease.

The effect of quercetin supplementation on clinical outcomes in COVID-19 patients: A systematic review and meta-analysis.

Coronavirus disease (COVID-19) affects both the respiratory system and the body as a whole. Natural molecules, such as flavonoid quercetin, as potential treatment methods to help patients combat COVID-19. The aim of this systematic review and meta-analysis is to give a comprehensive overview of the impact of quercetin supplementation on inflammatory factors, hospital admission, and mortality of patients with COVID-19. The search has been conducted on PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library using relevant keywords until August 25, 2023. We included randomized controlled trials (RCTs) comparing COVID-19 patients who received quercetin supplementation versus controls. We included five studies summarizing the evidence in 544 patients. Meta-analysis showed that quercetin administration significantly reduced LDH activity (standard mean difference (SMD): -0.42, 95% CI: -0.82, -0.02, I 2 = 48.86%), decreased the risk of hospital admission by 70% (RR: 0.30, 95% CI: 0.14, 0.62, I 2 = 00.00%), ICU admission by 73% (RR: 0.27, 95% CI: 0.09, 0.78, I 2 = 20.66%), and mortality by 82% (RR: 0.18, 95% CI: 0.03, 0.98, I 2 = 00.00%). No significant changes in CRP, D-dimmer, and ferritin were found between groups. Quercetin was found to significantly reduce LDH levels and decrease the risk of hospital and ICU admission and mortality in patients with COVID-19 infection.

Two-month period of 500 mg lecithin-based delivery form of quercetin daily dietary supplementation counterbalances chronic fatigue symptoms: A double-blind placebo controlled clinical trial

BackgroundChronic fatigue (CF) is a complex phenomenon without clear etiology that may require long-term treatment, but to date, no specific therapy has been identified for it. Some botanicals might be helpful in the management of CF. Among these botanicals, quercetin demonstrates its capacity to modulate multiple biological pathways and acknowledged major properties in CF: antioxidant, anti-inflammatory, immunomodulating, improving exercise endurance, enhancing mitochondrial biogenesis, repairing mitochondrial dysfunction. PurposeGiven this background, the aim of this study was to evaluate if a 2-month period of daily Quercetin Phytosome™ 500 mg supplementation is of benefit for the relief of CF. MethodsThe primary end point has been the evaluation of fatigue, by Fatigue Impact Scale (FIS-40). The secondary end points have been the assessment of sleep, by Pittsburgh Sleep Quality Index (PSQI), evaluation of muscle performance, by short physical performance battery and by wearable armband-shaped sensor in order to evaluate the number of steps, body composition, by DXA and quality of life by Short‐Form 12–Item Health Survey (SF‐12). ResultsSeventy-eight subjects (42 F; 36 M) (mean age 56 ± 9) reporting CF symptoms, completed the study (placebo/supplement 38/40). The FIS-40 mean difference changes between groups (supplement minus placebo) was − 10.583 points (CI95% −11.985; −9.182) (p < 0.001). Also, statistically significant changes between groups have been recorded in Pittsburgh Sleep Quality Index − 2.040 points (CI95%: −2.770; −1.309), p < 0.01), number of steps 1443.152 (CI95%: 1199.556; 1686.749), and SPPB (score) 0.248 (CI95%: 0.105; 0.391) (p < 0.001). ConclusionThe quercetin supplementation counterbalances CF symptoms.

The effects of Quercetin supplementation on cardiometabolic outcomes: An umbrella review of meta-analyses of randomized controlled trials.

Quercetin is a bioactive flavonoid, but the effect of it on cardiometabolic factors has remained uncertain and previous findings from meta-analyses have been controversial. To provide an overview of the effects of Quercetin on cardiometabolic factors based on meta-analyses of randomized controlled trials (RCTs). MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched to identify eligible publications. As part of the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. A GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to rate the certainty of evidence. Five meta-analyses including 18 eligible RCTs plus 5 RCTs that were not included in previous meta-analyses were found. The results indicated Quercetin does not affect diastolic blood pressure (DBP), lipid profile, inflammation, anthropometric indices, fasting plasma glucose (FBG), and homeostatic model assessment for insulin resistance (HOMA-IR). However, Quercetin supplementation could significantly reduce systolic blood pressure (SBP) (weighted mean difference (WMD): -1.9, 95% CI = -3.2 to -0.6, I2 = 88.3%) and insulin level (WMD: -1.07, 95% CI = -1.9 to -0.1, I2 = 75.0%). The certainty of evidence ranged from very low to moderate. Quercetin supplementation has reducing effects on SBP and insulin levels but not other cardiometabolic parameters. More high-quality trials with longer follow-up durations may be required to obtain a more robust conclusion.

Quercetin supplementation attenuates airway hyperreactivity and restores airway relaxation in rat pups exposed to hyperoxia.

Hyperoxia exposure of immature lungs contributes to lung injury and airway hyperreactivity. Up to now, treatments of airway hyperreactivity induced by hyperoxia exposure have been ineffective. The aim of this study was to investigate the effects of quercetin on hyperoxia-induced airway hyperreactivity, impaired relaxation, and lung inflammation. Newborn rats were exposed to hyperoxia (FiO2 > 95%) or ambient air (AA) for seven days. Subgroups were injected with quercetin (10 mg·kg-1·day-1). After exposures, tracheal cylinders were prepared for in vitro wire myography. Contraction to methacholine was measured in the presence or absence of organ bath quercetin and/or Nω-nitro-L-arginine methyl ester (L-NAME). Relaxation responses were evoked in preconstricted tissues using electrical field stimulation (EFS). Lung tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) levels were measured by enzyme-linked immunosorbent assay (ELISA). A P < 0.05 was considered statistically significant. Contractile responses of tracheal smooth muscle (TSM) of hyperoxic animals were significantly increased compared with AA animals (P < 0.001). Treatment with quercetin significantly reduced contraction in hyperoxic groups compared with hyperoxic control (P < 0.01), but did not have any effect in AA groups. In hyperoxic animals, relaxation of TSM was significantly reduced compared with AA animals (P < 0.001), while supplementation of quercetin restored the lost relaxation in hyperoxic groups. Incubation of preparations in L-NAME significantly reduced the quercetin effects on both contraction and relaxation (P < 0.01). Treatment of hyperoxic animals with quercetin significantly decreased the expression of TNF-α and IL-1β compared with hyperoxic controls (P < 0.001 and P < 0.01, respectively).The findings of this study demonstrate the protective effect of quercetin on airway hyperreactivity and suggest that quercetin might serve as a novel therapy to prevent and treat neonatal hyperoxia-induced airway hyperreactivity and inflammation.

Quercetin Alleviates Lipopolysaccharide-Induced Cell Oxidative Stress and Inflammatory Responses via Regulation of the TLR4-NF-κB Signaling Pathway in Bovine Rumen Epithelial Cells.

Subacute rumen acidosis (SARA) will cause an increase in endotoxin, which will have a negative effect on the bovine rumen epithelial cells (BREC). Flavonoids are effective in treating inflammation caused by endotoxin. Quercetin is a vital flavonoid widely occurring in fruits and vegetables and has received significant interest as a prospective anti-inflammatory antioxidant. Nonetheless, quercetin's protective machinery against such damage to BREC induced by lipopolysaccharide (LPS) remains unclear. A combined quercetin and LPS-induced BREC inflammation model was utilized to elucidate the effect of quercetin protecting BREC from LPS-induced injury. After treating BREC with different doses of LPS (1, 5, and 10 μg/mL) for 6 h or 24 h, the mRNA expression of inflammatory factors was detected. Our experimental results show the establishment of the BREC inflammation model via mRNA high expression of pro-inflammatory cytokines in BREC following 6 h treatment with 1 µg/mL LPS. The promotive effect of 80 μg/mL quercetin on BREC growth via the cell counting kit-8 (CCK8) assay was observed. The expression of pro-inflammatory cytokines and chemokines, notably tumor necrosis factor α (TNF-α), Interleukin 1β (IL-1β), IL-6, CC-motif chemokine ligand 2 (CCL2), CCL20, CCL28, and CXC motif chemokine 9 (CXCL9), etc., was significantly reduced by quercetin supplementation. We also analyzed the mRNA detection of related pathways by qRT-PCR. Our validation studies demonstrated that quercetin markedly curbed the mRNA expression of the toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the nuclear factor-κB (NF-κB) in LPS-treated BREC. In addition, western blot result outcomes confirmed, as expected, that LPS significantly activated phosphorylation of p44/42 extracellular regulated protein kinases (ERK1/2) and NF-κB. Unexpectedly, this effect was reversed by adding quercetin. To complement western blot results, we assessed p-ERK1/2 and p-p65 protein expression using immunofluorescence, which gave consistent results. Therefore, quercetin's capacity to bar the TLR4-mediated NF-κB and MAPK signaling pathways may be the cause of its anti-inflammatory effects on LPS-induced inflammatory reactions in BREC. According to these results, quercetin may be utilized as an anti-inflammatory medication to alleviate inflammation brought on by high-grain feed, and it also lays out a conceptual foundation regarding the development and utilization of quercetin in the later stage.

Quercetin improves white adipose tissue redox homeostasis in ovariectomized rats.

Estrogen deficiency is a well-known hallmark of menopause and is associated with oxidative stress and metabolic dysfunction. Quercetin (Q), a flavonoid found in fruits and vegetables, has demonstrated anti-inflammatory effects in experimental models of metabolic disorders. In this study, we aimed to investigate the effects of quercetin on retroperitoneal white adipose tissue (rWAT) redox homeostasis and systemic metabolic parameters in ovariectomized (OVX) rats. Female Wistar rats at 3 months old were divided into the following experimental groups: sham-operated treated with vehicle (DMSO 10% + PBS - 1 mL/kg); OVX (vehicle treated) and OVX-Q (25 mg/kg) - via oral gavage, daily for 5 weeks. Q did not prevent weight gain but improved glucose tolerance and blood cholesterol profile, and attenuated uterine atrophy in OVX rats. Furthermore, Q had a protective effect on rWAT, once the OVX-Q group presented lower oxidative stress levels, and reduced levels of the pro-inflammatory cytokine tumor necrosis factor alpha, compared to the OVX group. Q improved antioxidant enzyme activities such as superoxide dismutase and catalase and decreased reactive oxygen species production, in OVX-Q rats. It was followed by increased levels of total thiol content and lower lipid peroxidation. Moreover, Q reduced senescent-related genes p16INK4a and p19ARF expression which were higher in the OVX group. In conclusion, quercetin supplementation improved redox homeostasis and reduced senescence-related markers, and inflammation in rWAT, which was reflected in preserved systemic metabolic health parameters in OVX rats. These findings suggest that quercetin may have therapeutic potential for the management of metabolic disorders associated with menopause-induced estrogen deficiency.

Quercetin and catechin supplementation provide protection against arsenic and mancozeb-induced toxicity in Wistar rats

The study was designed to determine the ameliorative potential of quercetin and catechin against the toxicity induced by co-exposure to Mancozeb (MZ) and arsenic in Wistar rats. Sixty-adult male Wistar rats were randomly divided into 10 groups (n=6). Group I served as control and group II was exposed to MZ [800 mg/kg, PO (per OS)]. Groups III, IV, and V were given drinking water containing sodium arsenite at the rate of 10, 50, and 100 ppb, respectively, for 28 days. Groups VI, VII, and VIII were treated with sodium arsenite in drinking water at 10, 50, and 100 ppb, respectively, along with MZ (800 mg/kg) for 28 days. Groups IX and X were given drinking water mixed with sodium arsenite at 100 ppb, MZ at 800 mg/kg, and quercetin (50 mg/kg) and catechin (50 mg/kg), respectively. Co-exposure to the toxicants (MZ and arsenic) significantly (P<0.05) aggravated the oxidative stress-induced alterations and the histopathological changes induced by individual toxicants. Supplementation of quercetin or catechin markedly attenuated the variations in nitric oxide levels and oxidative biomarkers in blood and the brain and shielded the histomorphology of the brain against oxidative damage.

Recent Advances in Potential Health Benefits of Quercetin.

Quercetin, a flavonoid found in fruits and vegetables, has been a part of human diets for centuries. Its numerous health benefits, including antioxidant, antimicrobial, anti-inflammatory, antiviral, and anticancer properties, have been extensively studied. Its strong antioxidant properties enable it to scavenge free radicals, reduce oxidative stress, and protect against cellular damage. Quercetin's anti-inflammatory properties involve inhibiting the production of inflammatory cytokines and enzymes, making it a potential therapeutic agent for various inflammatory conditions. It also exhibits anticancer effects by inhibiting cancer cell proliferation and inducing apoptosis. Finally, quercetin has cardiovascular benefits such as lowering blood pressure, reducing cholesterol levels, and improving endothelial function, making it a promising candidate for preventing and treating cardiovascular diseases. This review provides an overview of the chemical structure, biological activities, and bioavailability of quercetin, as well as the different delivery systems available for quercetin. Incorporating quercetin-rich foods into the diet or taking quercetin supplements may be beneficial for maintaining good health and preventing chronic diseases. As research progresses, the future perspectives of quercetin appear promising, with potential applications in nutraceuticals, pharmaceuticals, and functional foods to promote overall well-being and disease prevention. However, further studies are needed to elucidate its mechanisms of action, optimize its bioavailability, and assess its long-term safety for widespread utilization.

Supplementation of flavonoids and inulin in Totoaba macdonaldi: Microbiota, liver gene expression and growth performance responses

Totoaba macdonaldi is an endemic, vulnerable, carnivorous fish of the Gulf of California that is currently being cultivated in northwestern Mexico for commercial and conservation purposes. The challenge for aquaculture of Totoaba is finding a diet that meets the protein requirements at an acceptable price and does not compromise its overall performance. Current diets in aquaculture are either prejudicial for the environment or have caused adverse effects on the digestive system and liver of Totoaba. To counteract those negative effects, this study evaluates quercetin and epicatechin supplementation in two doses (0.25% and 0.5%), with and without inulin, as functional additives. A total of 360 juveniles were divided into 18 tanks and fed with six experimental diets in triplicate. Growth performance, intestinal microbiota, blood biochemistry, and liver transcriptomics were evaluated. The liver’s transcriptome de novo assembly had an N50 of 2599 bp and 76.38% BUSCO completeness. Experimental diets showed higher growth performance than the control diet (p < 0.05). The lowest concentrations of triglycerides and cholesterol were observed in fish fed with Inulin (I), Flavonoids at 0.5% (FH), and Flavonoids at 0.5% + Inulin (IFH). In the liver, Flavonoids at 0.25% (FL) and IFH diets presented down regulated genes related to metabolic and biosynthetic processes, whereas FH and Inulin diets presented upregulated genes related to cellular and growth processes. Additionally, the FH diet presented a greater abundance of Lactobacillaceae and a reduction of Enterococcus faecalis and Vibrio anguillarum in the intestinal microbiome. The present results found that flavonoids and inulin improve metagenomic diversity at the intestinal level by increasing the abundance of beneficial bacteria. This leads to a reciprocal interaction improving the absorption of flavonoids, reducing fat absorption in the gastrointestinal tract, enhancing gene modulation of metabolic processes involved in lipid oxidation.

Quercetin supplementation in the diet of Labeo rohita: Effects on growth, proximate composition, antioxidative indices and immunity

This experiment was conducted to investigate the effects of quercetin supplementation on the growth performance, antioxidant indices, and immunity of Labeo rohita. Five experimental diets were formulated with quercetin inclusion rates of 0 g/kg (T0, control), 2 g/kg (T2), 4 g/kg (T4), 6 g/kg (T6), and 8 g/kg (T8). Fish (N = 300) with an average initial weight of 12.8 ± 0.07 g were fed with one of the five diets for 90 days. At the end of experiment, the highest (p < 0.05) final weight (FW), absolute weight gain (AWG%), weight gain percentage (WG%) and specific growth rate (SGR) was observed in group fed the diet containing 4 g/kg quercetin. The best (p < 0.05) feed conversion ratio (FCR) was noted at 4 g/kg quercetin supplemented diet. Body indices such as viscerosomatic index (VSI) and hepatosomatic index (HSI) remained unaffected (p > 0.05). The muscle proximate composition was non-significantly (p > 0.05) affected by quercetin supplementation. The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) tended to increase (p < 0.05) with increasing quercetin levels. However, an opposite trend (p < 0.05) was recorded in thiobarbituric acid reactive substance (TBARS). The immune parameters including lysozyme (LYZ), immunoglobulin (IgM) and alkaline phosphatase activity (AKP) were significantly enhanced (p < 0.05) up to 4 g/kg quercetin supplementation and decreased (p < 0.05) thereafter. The optimal dietary quercetin level for maximum WG% of L. rohita was determined as 4.11 g/kg through broken line regression analysis. In conclusion, quercetin supplementation up to 4.11 g/kg is recommended for better growth performance, antioxidant capacity, and immunity of L. rohita.

The ameliorative effects of quercetin and curcumin against subacute nephrotoxicity of fipronil induced in Wistar rats.

Fipronil is a phenylpyrazole insecticide that is widely used in agricultural, veterinary, and public health fields for controlling a wide variety of insect species and it is an environmentally potent toxic substance. Curcumin and quercetin, which are well-known natural antioxidants, are widely used to prevent the harmful effects of free radicals on biological systems. The present study aimed to determine the potential ameliorative effects of quercetin and/or curcumin on fipronil-induced nephrotoxicity in rats. Curcumin (100mg/kg of body weight), quercetin (50mg/kg of body weight), and fipronil (3.88mg/kg of body weight) were administered to male rats by intragastric gavage for 28 consecutive days. In the present study, body weight, kidney weight, the renal function markers (blood urea nitrogen, creatinine, and uric acid levels) in the blood, antioxidant enzyme activities, and malondialdehyde level as markers of oxidative stress, and histological changes of the renal tissue were evaluated. The levels of serum blood urea nitrogen, creatinine, and uric acid were significantly increased in fipronil-treated animals. Additionally, while superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase activities were decreased in the kidney tissue of rats treated with fipronil, malondialdehyde level was significantly increased. Histopathological analyses showed that the glomerular and tubular injury occurred in the renal tissue of fipronil-treated animals. Also, the supplementation of quercetin and/or curcumin with fipronil significantly improved fipronil-induced alterations in renal function markers, antioxidant enzyme activities, malondialdehyde levels, and histological features of renal tissue.

Protective effect of quercetin on avermectin induced splenic toxicity in carp: Resistance to inflammatory response and oxidative damage

Avermectin pollution is an important problem that cannot be ignored in aquatic system in recent years. It has brought great trouble to freshwater aquaculture, especially fishery aquaculture. Plant-derived quercetin has anti-inflammatory and antioxidant properties and is widely used as a dietary additive, but its protective effect on immune damage induced by avermectin in freshwater carp remains unclear. This study evaluated the role of dietary additive quercetin supplementation in chronic avermectin exposure of carp spleen. Sixty carp were divided into 4 groups (n = 15/ group), including control group, avermectin treatment group, quercetin treatment group, quercetin and avermectin co-treatment group. Carp were exposed to a 1/10 96 h LC50 dose of avermectin for 30 d and fed a carp diet containing 400 mg/kg quercetin twice a day (3% body weigh/ carp). The results showed that chronic avermectin exposure caused the loose parenchymal structure of carp spleen tissue and the increase of inflammatory cells, accompanied by increased transcription levels of pro-inflammatory il-1β, il-6, tnf-α and decreased levels of anti-inflammatory factors il-10 and tgf-β1, ROS accumulation in spleen tissue. MDA content increased and T-AOC, CAT and GSH levels decreased. Quercetin down-regulates the NF-κB pathway by inhibiting the expression of iNOS and activating p38 MAPK, blocking the transcription of inflammatory factors, and alleviating the inflammation of carp spleen caused by chronic avermectin exposure. In addition, quercetin inhibits the over-activation of Nrf2/Keap-1 signaling axis, blocks ROS accumulation, and restores the spleen REDOX homeostasis. In conclusion, quercetin, as a dietary additive for carp feed, can effectively improve the immune damage caused by avermectin pollution in aquatic environment, resist spleen inflammation and oxidative stress, and provide a theoretical basis for clinical development of freshwater carp feed.

Dietary quercetin protects Cherax quadricarinatus against white spot syndrome virus infection

Quercetin is a plant flavonoid with a molecular formula C15H10O7. It has antioxidant, anti-inflammatory, antibacterial, and anti-apoptotic effects in animals. We used red claw crayfish (Cherax quadricarinatus) infected with white spot syndrome virus (WSSV) to investigate quercetin's effects on innate immunity of crustaceans. Quercetin supplementation significantly reduced the mortality of crayfish caused by WSSV infection and the number of VP28 copies in WSSV-infected crayfish. Quantitative real-time PCR analysis showed that dietary quercetin supplementation increased the expression of immune-related genes, like JAK, STAT and ALF. Quercetin supplementation affected the activity of six immune-related enzymes and increased the total number of hemocytes in crayfish. It also significantly reduced the rate of hemocyte apoptosis in both WSSV-infected and uninfected crayfish. These results demonstrate the potential for commercial use of quercetin for the prevention of WSSV disease in crustaceans.

Effects of quercetin supplementation on endothelial dysfunction biomarkers and depression in post-myocardial infarction patients: A double-blind, placebo-controlled, randomized clinical trial

Endothelial dysfunction and depression are highly prevalent in patients who have experienced a myocardial infarction (MI). Epidemiological studies have pointed out that a diet rich in flavonoids, e.g., quercetin, can prevent the development of these biological phenomena. Therefore, we aimed to investigate the effects of quercetin supplementation on the levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) and on depression in post-MI subjects. Eighty-eight post-MI patients who had experienced their first MI (body mass index ≤35kg/m2, age 30-65 years) were recruited from the Rasool-e-Akram and Afshar Hospitals, Iran, and included in this randomized, placebo-controlled, double-blind parallel study. The participants were randomly assigned to receive a daily dose of 500mg quercetin (n=44) or placebo (n=44) for 8 weeks. Serum concentrations of ICAM-1 and VCAM-1 were quantified by ELISA and depression levels were assessed using the Beck's Depression Inventory (BDI-II) questionnaire at baseline and at 8-week follow-up. Seventy-six participants completed the study, but the intention-to-treat (ITT) analysis was conducted for all 88 participants who were randomized into the intervention groups. No significant changes in serum concentrations of ICAM-1 or VCAM-1 (P=0.21 and P=0.80, respectively) were observed after 8 weeks of quercetin supplementation versus placebo. In addition, depression levels did not differ significantly between the quercetin and placebo groups. Our findings demonstrated that in post-MI patients, daily supplementation with quercetin (500mg/day) for 8 weeks did not affect endothelial dysfunction biomarkers and depression levels. This trial was registered at IRCT.ir as IRCT20190428043405N1.

Quercetin alleviates atherosclerosis by suppressing oxidized LDL-induced senescence in plaque macrophage via inhibiting the p38MAPK/p16 pathway

Quercetin is a widely known and biologically active phytochemical and exerts therapeutic effects against atherosclerosis. The removal of senescent plaque macrophages effectively slows the progression of atherosclerosis and decreases the plaque burden. Still, whether quercetin alleviates atherosclerosis by inhibiting the senescence of plaque macrophages, including the potential mechanisms, remains unclear. ApoE−/− mice were fed with a normal chow diet or high-fat diet (HFD) supplemented or not with quercetin (100 mg/kg of body weight) for 16 weeks. An accumulation of senescent macrophages was observed in the plaque-rich aortic tissues from the mice with HFD, but quercetin supplementation effectively reduced the amount of senescent plaque macrophage, inhibited the secretion of key senescence-associated secretory phenotype factors, and alleviated atherosclerosis by inhibiting p38MAPK phosphorylation and p16 expression. In vitro, SB203580 (a specific inhibitor of p38 MAPK) significantly inhibited oxidized low-density lipoprotein (ox-LDL)-induced senescence in mouse RAW264.7 macrophages, as evidenced by decreased senescence-associated markers (SA-β-gal staining positive cells and p16 expression). Furthermore, quercetin not only effectively reversed ox-LDL-induced senescence in RAW264.7 cells but also decreased the mRNA levels of several key senescence-associated secretory phenotype factors by suppressing p38 MAPK phosphorylation and p16 expression. The p38 MAPK agonist Asiatic acid reversed the effects of quercetin. In conclusion, these findings indicate that quercetin suppresses ox-LDL-induced senescence in plaque macrophage and attenuates atherosclerosis by inhibiting the p38 MAPK/p16 pathway. This study elucidates the mechanisms of quercetin against atherosclerosis and supports quercetin as a nutraceutical for the management of atherosclerosis.

Effect of Six Weeks of Aerobic Training with Quercetin Supplementation on the Expression of Mitochondrial AMPK and NRF-1 Genes in the Hippocampus of Diabetic Male Rats

Effect of Six Weeks of Aerobic Training with Quercetin Supplementation on the Expression of Mitochondrial AMPK and NRF-1 Genes in the Hippocampus of Diabetic Male Rats

Hypobaric hypoxia induced renal injury in rats: Prophylactic amelioration by quercetin supplementation.

The present study aims at assessing the effect of hypobaric hypoxia induced renal damage and associated renal functions in male SD rats. Further, this study was extended to explore the protective efficacy of quercetin in ameliorating the functional impairment in kidneys of rats under hypobaric hypoxia. Rats were exposed to 7620m (25000 ft.) at 25°C ±2 in a simulated hypobaric hypoxia chamber for different time durations (0h,1h, 3h, 6h, 12h, 24h and 48h) in order to optimize the time at which maximum renal damage would occur. The rats were exposed to hypoxia for 12h duration was considered as the optimum time, due to significant increase in oxidative stress (ROS, MDA) and renal metabolites (creatinine, BUN and uric acid) with remarkable reduction (p<0.001) in antioxidants (GSH) in plasma, as compared to other tested durations. Moreover, these findings were in support with the histopathology analysis of renal tissues. For optimum quercetin dose selection, the rats were administered with different doses of quercetin (25mg, 50mg, 100mg and 200mg/Kg BW) for 12h at 7620 m, 25°C ±2, 1h prior to hypoxia exposure. Quercetin 50mg/kg BW was considered as the optimum dose at which significant (p<0.001) reduction in oxidative stress levels followed by reduction in creatinine and BUN levels were obtained in plasma of the rats compared to hypoxia control rats. Quercetin prophylaxis (50mg/kg BW) stabilized the HIF-1α protein expression followed by reduced VEGF protein expression along with reduced levels of LDH (p<0.001) in the kidneys of rats compared to hypoxia control. Histopathological observations further substantiated these findings in reducing the renal tissue injury. The study findings revealed that, quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced renal injury by reducing the oxidative stress in rats.