Oral Administration Of Quercetin Research Articles

Triazophos-induced spermotoxicity in rats: Protective effects of nano-quercetin

This study aimed to evaluate the spermotoxic potential of triazophos in rats and to check the possible shielding effect of quercetin and nano-quercetin against triazophos-induced toxicity. Rats in Group I were given olive oil as a vehicle. Group II and Group III received high-dose and low-dose triazophos, respectively. Oral administration of quercetin (Group IV) and nano-quercetin (Group VI) at a dose of 50 mg/kg body weight was given to two additional groups of animals. Two other high-dose triazophos groups were co-administered with quercetin (Group V) and nano-quercetin (Group VII).Triazophos administration for 60 days in rats altered the structural and functional parameters of spermatozoa and brought about a decline in total sperm count, percentage of viable sperms, drop in sperm motility, and decrease in the number of sperms showing normal morphology. It also decreased the number of spermatozoa with intact acrosomes and HOST-positive spermatozoa. Further, triazophos increased the levels of reactive oxygen species and triggered apoptotic pathways in spermatozoa in a dose-dependent manner. It decreased daily sperm production and caused histomorphological aberrations in the epididymis and vas deferens. Co-administration of nano-quercetin with triazophos effectively counteracted sperm-related pathological changes. Nano-quercetin offered better protection over quercetin in ameliorating the triazophos-induced spermotoxicity in rats.

P10-26 Effect of oral administration of Quercetin on reproductive damage caused by acrylamide exposure in rats

P10-26 Effect of oral administration of Quercetin on reproductive damage caused by acrylamide exposure in rats

Mitigating Doxorubicin-Induced Cardiotoxicity through Quercetin Intervention: An Experimental Study in Rats.

Doxorubicin (DOX) is an effective anticancer drug, but its use is limited by dose-dependent heart toxicity. Quercetin is a natural antioxidant frequently studied for its beneficial properties. Moreover, a wide range of dietary supplements are available for human use. This in vivo study aimed to explore the potential cardioprotective effects of quercetin in chronic DOX treatment. A total of 32 Wistar rats were randomly divided into four groups: control, DOX, DOX/Q-50, and DOX/Q-100, treated with saline, 2.5 mg/kg body-weight DOX, 2.5 mg/kg body-weight DOX + 50 mg quercetin, and 2.5 mg/kg body-weight DOX + 100 mg quercetin, respectively, for two weeks. Rats were monitored using cardiac ultrasound (US) and markers for cardiac injury. Oxidative damage and ultrastructural changes in the heart were investigated. Chronic DOX treatment led to a decline in cardiac function and elevated values of NT pro-BNP, troponin I, and CK-MB. Quercetin treatment slightly improved certain US parameters, and normalized serum NT pro-BNP levels. Furthermore, DOX-induced SOD1 depletion with consequent Nrf2 activation and DNA damage as shown by an increase in γH2AX and 8HOdG. Quercetin treatment alleviated these alterations. Oral administration of quercetin alleviated serum markers associated with DOX-induced cardiotoxicity. Furthermore, it exhibited a favorable impact on the cardiac US parameters. This suggests that quercetin may have potential cardioprotective properties.

Quercetin activates energy expenditure to combat metabolic syndrome through modulating gut microbiota-bile acids crosstalk in mice

ABSTRACT Abdominal obesity-related metabolic syndrome (MetS) has emerged as a significant global public health issue that affects human health. Flavonoids, such as quercetin, have been reported to exert obvious anti-obesity and lipid-lowering effects in both humans and animal models. However, the precise underlying mechanism remains elusive. In this study, we investigated the potential roles of gut microbiota-bile acids (BAs) interactions in quercetin-induced anti-obesity effects and metabolic benefits. Oral administration of quercetin significantly enhanced energy metabolism through activating thermogenesis of brown adipose tissues (BAT) and browning of white adipose tissues (WAT), thus mitigating metabolic dysfunctions in an abdominal obesity-related MetS mouse model. Further mechanistic studies demonstrated that quercetin treatment substantially promoted the generation of non-12α-hydroxylated BAs (non-12OH BAs), particularly ursodeoxycholic acid (UDCA) and lithocholic acid (LCA), in serum via regulating the overall structure of gut microbiota and enriching Lactobacillus. High level of non-12OH BAs bind to Takeda G protein-coupled receptor 5 (TGR5) on adipocytes to stimulate thermogenesis. Remarkably, fecal microbiota transplantation (FMT) from quercetin-treated mice replicated the effects of quercetin on non-12OH BAs generation and energy expenditure, which suggested gut microbiota reshape and concomitant BAs regulation were responsible for the benefits on energy metabolism of quercetin in the MetS mouse model. Our findings not only highlighted the critical role of gut microbiota-BAs crosstalk in mediating quercetin-induced energy expenditure, but also enriched the pharmacological mechanisms of quercetin in ameliorating MetS-related diseases.

Oral administration of quercetin and fisetin potentiates photocarcinogenesis in UVR-exposed hairless mice

Background: Phytochemicals have demonstrated great potential as photoprotectants. Apple-derived compounds such as quercetin, fisetin, and rutin are reported to provide topical photoprotection, but oral delivery has not been explored. Purpose: To determine the photoprotective effects of oral administration of quercetin, fisetin, and rutin, and their accumulation in skin assessed through mass spectrometry imaging. Study design: Groups of 25 hairless mice (n = 125 mice) received in the daily feed 100 mg/kg quercetin, fisetin, or rutin, 600 mg/kg nicotinamide in water as a positive control, or no supplementation as the UV control. The animals were exposed to ultraviolet radiation (UVR) equivalent to 3.5 standard erythema doses thrice weekly. Method: Mass spectroemetry imaging was used to assess local skin accumulation. Results: Oral administration of quercetin and fisetin reduced the time to tumour onset (Quercetin: second and third tumour [p < 0.045]; fisetin: third tumour [p < 0.021]), with no observed effect for rutin. Nicotinamide delayed the onset of all three recorded tumours (p < 0.0082). Results were supported by accelerated tumour growth following quercetin treatment (p < 0.0069), whereas nicotinamide reduced tumour growth (p < 0.00015). Skin accumulation of the compounds could not be demonstrated, suggesting other mechanisms must be explored to explain these effects on UVR-induced carcinogenesis. Conclusion: Oral administration of quercetin and fisetin to hairless mice increased UVR-induced tumour development. These results indicate a need for caution when selecting candidates for photoprotectants.

Investigating the Potential Hepatoprotective Effect of Quercetin in Male Rats ‎Following Acute Exposure to Cyclophosphamide

This study aimed to assess the hepatoprotective efficacy of quercetin against ‎hepatotoxicity ‎induced by cyclophosphamide in a rat model. A total of 28 male ‎Wister albino rats (Rattus ‎norvegicus), with body ‎weights ranging from 195.5 to ‎‎198.2 g and approximately three months ‎of age, were randomized into four different ‎groups: the untreated Control group ‎received no interventions; the CYP group was treated with an intraperitoneal ‎injection of ‎cyclophosphamide at a dose of 200 mg/BW; the Qt group received an ‎‎oral administration of quercetin at 100 mg/kg BW daily for ten days; and the combined (Qt+CYP) group received quercetin orally for ten days, followed by a ‎cyclophosphamide ‎injection on the tenth day. Various biochemical markers, ‎including alanine aminotransferase ‎‎(ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and liver glutathione ‎‎(GSH), and malondialdehyde ‎‎(MDA), were analyzed, in addition to body weight and ‎prothrombin time. The ‎Untreated Control group exhibited baseline levels for all assessed ‎markers. In ‎contrast, the CYP group showed elevated levels of ALT, AST, ‎‎ALP, and MDA, coupled with a decrease in GSH. Notably, the Qt+CYP ‎group ‎demonstrated a statistically significant reduction (P‎‎&lt;0.05) in ALT, AST, ALP, ‎and MDA levels, ‎as well as an increase in GSH and prothrombin time, when ‎compared to the CYP group. No significant differences in body ‎weight were observed across all groups ‎‎(P‎‎&lt;0.05). The results of the study indicate that quercetin has the potential to be used as a ‎‎hepatoprotective agent, protecting liver tissues from the cytotoxic effects of cyclophosphamide.

Quercetin-Induced Enhancement of Nasal Epithelial Cells' Ability to Produce Clara Cell 10-kD Protein In Vitro and In Vivo.

Background: Quercetin, a polyphenolic flavonoid found in various plants and foods, is known to have antioxidant, antiviral and anticancer effects. Although quercetin is well known to exert anti-inflammatory and anti-allergic effects, the precise mechanisms by which quercetin favorably modifies the clinical status of allergic diseases, such as allergic rhinitis (AR), remain unclear. The present study examined whether quercetin could modulate the production of the endogenous anti-inflammatory molecule, Clara cell 10-kD protein (CC10), in vitro and in vivo. Methods: Human nasal epithelial cells (1 × 105 cells/mL) were stimulated with 20 ng/mL of tumor necrosis factor-alpha (TNF) in the presence of quercetin for 24 h. CC10 levels in culture supernatants were examined by ELISA. Sprague Dawley rats were sensitised with toluene 2,4-diisocyanate (TDI) by intranasal instillation of 10% TDI in ethyl acetate at a volume of 5.0 μL once daily for five days. This sensitisation procedure was repeated after an interval of two days. The rats were treated with different dosages of quercetin once daily for five days starting on the 5th day following the second sensitization. Nasal allergy-like symptoms induced by the bilateral application of 5.0 μL of 10% TDI were assessed by counting sneezing and nasal-rubbing behaviours for 10 min immediately after the TDI nasal challenge. The levels of CC10 in nasal lavage fluids obtained 6 h after TDI nasal challenge were examined using ELISA. Results: The treatment of cells with low doses of quercetin (<2.5 μM) scarcely affected TNF-induced CC10 production from nasal epithelial cells. However, the ability of nasal epithelial cells to produce CC10 after TNF stimulation significantly increased on treatment with quercetin doses (>5.0 μM). The oral administration of quercetin (>25 mg/kg) for five days significantly increased the CC10 content in nasal lavage fluids and attenuated the nasal symptoms induced by the TDI nasal challenge. Conclusions: Quercetin inhibits AR development by increasing the ability of nasal epithelial cells to produce CC10.

Quercetin ameliorates acute acrylamide induced spleen injury

ABSTRACT Acrylamide is used for industrial and laboratory purposes; it also is produced during cooking of carbohydrate-rich food at high temperature. We investigated the therapeutic potential of quercetin for treatment of acute acrylamide induced injury to the spleen. We used female albino rats treated with acrylamide for 10 days followed by oral administration of quercetin in three doses for 5 days. We observed significantly reduced total body weight, spleen weight, red blood cells, total proteins, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phophate dehydrogenase, reduced glutathione, concentration of serum IgG and IgM after acrylamide induced toxicity compared to controls. We also found that white blood cells, triglycerides, cholesterol and lipid oxidation were increased significantly after acrylamide induced toxicity in rats compared to controls. Histoarchitecture of spleen was affected adversely by acrylamide toxicity. Administration of quercetin ameliorated adverse effects of acrylamide in a dose-dependent manner. Quercetin appears to ameliorate acrylamide induced injury to the spleen by increasing endogenous antioxidants and improving histoarchitecture and immune function.

Preventive effect of quercetin-Loaded nanophytosome against autistic-like damage in maternal separation model: The possible role of Caspase-3, Bax/Bcl-2 and Nrf2

The autism is an abnormality in the neuronal advance which starts before age 3 recognized by defective behaviors. This study aimed to make quercetin-loaded nanophytosomes (QNP) on behavioral deficits, cerebellar oxidative stress and apoptosis in an autistic-like model caused by maternal separation (MS). The newborn rats are randomly categorized into seven groups, including control, positive control, disease, and diseases treated with quercetin (10 and 40 mg/kg) and QNP (10 and 40 mg/kg). Pups exposed to MS for 3 h per day from postnatal days (PND) 1–9 showed behavioral impairment in adult rats compared to control group. The oral administration of quercetin and QNP was constantly started after the lactation period (21 postnatal days) for three weeks. Autistic-like behaviors, antioxidant parameters, and Nrf2, Bax/Bcl-2, and Caspase-3 expressions were surveyed in the cerebellum. Quercetin (40 mg/kg) treated improved some behavioral disorders. Also, the improvement of oxidative stress parameters, Nrf2 and apoptotic factors gene expression was observed in the cerebellum of quercetin (40 mg/kg) treated (p < 0.01). QNP treatment (10 and 40 mg/kg) significantly ameliorated anxiety-like behaviors, line crossing, and grooming index (p < 0.001), lipid peroxidation (p < 0.001), and increased catalase (CAT) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione peroxidase (GPx) (p < 0.001) activity, and glutathione (GSH) levels (p < 0.05). Moreover, QNP significantly reduced Caspase-3 and Bax expression (p < 0.001), but increased Bcl-2, and Nrf2 expressions (p < 0.001). These findings indicated that QNP due to its high bioavailability was more effective than quercetin can be reduced autistic-like behavior, oxidative and apoptotic damages in the model of MS rats.

Identification and Functional Evaluation of Polyphenols That Induce Regulatory T Cells.

Regulatory T cells (Tregs) and CD4+/CD25+ T cells play an important role in the suppression of excessive immune responses, homeostasis of immune function, and oral tolerance. In this study, we screened for food-derived polyphenols that induce Tregs in response to retinaldehyde dehydrogenase (RALDH2) activation using macrophage-like THP-1 cells. THP-1 cells were transfected with an EGFP reporter vector whose expression is regulated under the control of mouse Raldh2 promoter and named THP-1 (Raldh2p-EGFP) cells. The THP-1 (Raldh2p-EGFP) cells were treated with 33 polyphenols after inducing their differentiation into macrophage-like cells using phorbol 12-myristate 13-acetate. Of the 33 polyphenols, five (kaempferol, quercetin, morin, luteolin and fisetin) activated Raldh2 promoter activity, and both quercetin and luteolin activated the endogenous Raldh2 mRNA expression and enzymatic activity. Furthermore, these two polyphenols increased transforming growth factor beta 1 and forkhead box P3 mRNA expression, suggesting that they have Treg-inducing ability. Finally, we verified that these polyphenols could induce Tregs in vivo and consequently induce IgA production. Oral administration of quercetin and luteolin increased IgA production in feces of mice. Therefore, quercetin and luteolin can induce Tregs via RALDH2 activation and consequently increase IgA production, suggesting that they can enhance intestinal barrier function.

Negligible Effect of Quercetin in the Pharmacokinetics of Sulfasalazine in Rats and Beagles: Metabolic Inactivation of the Interaction Potential of Quercetin with BCRP.

Breast cancer resistance protein (BCRP) mediates pharmacokinetic drug interactions. This study evaluated the potential of quercetin to inhibit and induce BCRP in vitro and in vivo. The inhibition of BCRP was investigated for quercetin and its metabolites using BCRP/mBcrp1-overexpressing MDCKII cells by flow cytometry. The induction of BCRP was investigated in LS174T cells using quantitative PCR. The expression of rat BCRP in rat small intestine, liver, and kidney was also measured after multiple administrations of quercetin in rats (50, 100, and 250 mg/kg, seven days). The in vivo pharmacokinetic changes of sulfasalazine following single or multiple administration of quercetin in rats and beagles were investigated. Although the induction effect of quercetin on BCRP was observed in vitro, the in vivo expression of rat BCRP was not changed by multiple quercetin administrations. Oral administration of quercetin did not affect the plasma concentration or pharmacokinetic parameters of sulfasalazine, regardless of dose and dosing period in either rats or beagles. In addition, the inhibitory effect of quercetin metabolites on BCRP/mBcrp1 was not observed. These results suggest that the in vivo drug interaction caused by quercetin via BCRP was negligible, and it may be related to the metabolic inactivation of quercetin for the inhibition of BCRP.

Oral Administration of Quercetin or Its Derivatives Inhibit Bone Loss in Animal Model of Osteoporosis.

Objectives. Quercetin (Q) and its derivatives are the major members of the naturally occurring flavonoid family, which possess beneficial effects on disease prevention including osteoporosis. The present study is aimed at further investigating the efficacy of the Q and its derivatives on bone pathology, bone-related parameters under imageology, bone maximum load, and serum bone metabolism indexes in animal model of osteoporosis. Potential mechanisms of Q and its derivatives in the treatment of osteoporosis as well as the existing problems regarding the modeling method and limitations of researches in this area were also summarized. Eight databases were searched from their inception dates to February 2020. Nineteen eligible studies containing 21 comparisons were identified ultimately. The risk of bias and data on outcome measures were analyzed by the CAMARADES 10-item checklist and Rev-Man 5.3 software separately. The results displayed the number of criteria met varied from 3/10 to 7/10 with an average of 5.05. The present study provided the preliminary preclinical evidence that oral administration of Q or its derivatives was capable of improving bone pathology, bone-related parameters under imageology and bone maximum load, increasing serum osteocalcin, alkaline phosphatase, and estradiol, and reducing serum c-terminal cross-linked telopeptide of type I collagen (P < 0.05). No statistical difference was seen in survival rate, index of liver, or kidney function (P > 0.05). Q and its derivatives partially reverse osteopenia probably via antioxidant, anti-inflammatory, promoting osteogenesis, inhibiting osteoclasts, and its estrogen-like effect. The findings reveal the possibility of developing Q or its derivatives as a drug or an ingredient in diet for clinical treatment of osteoporosis.

Bioavailability and metabolic pharmacokinetics of rutin and quercetin in rats

Rutin and quercetin, a flavone glycoside and its aglycone, are the flavonoids most widely and abundantly present in herbs and plant The aim of this study was to characterize and compare the bioavailability and metabolic pharmacokinetics of rutin and quercetin in rats. Quercetin was administered intravenously (33 μmol/kg) and orally (165 μmol/kg), while rutin was administered only orally (328 μmol/kg) to rats. Blood samples were withdrawn via cardiopuncture at specific time points. An HPLC method was used to determine the concentrations of quercetin before and after hydrolysis using β-glucuronidase and sulfatase, respectively. The pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN. The results showed that after intravenous administration of quercetin, 93.8% of the dose was circulating as its sulfates and glucuronides. After oral administration of quercetin, the glucuronides and sulfates of querectin were exclusively present in the bloodstream, whereas the parent form of quercetin was not detected. The oral absorption rate of quercetin was 53% compared to intravenous administration after dose correction. When rutin was orally administered, sulfates and glucuronides of quercetin were exclusively present in the bloodstream, whereas rutin and quercetin were not detected. Quercetin showed higher oral absorption rate than rutin. In conclusion, quercetin sulfates and quercetin glucuronides represent the major metabolites either rutin or quercetin was administered to rats.

Oral supplementation of quercetin in PRRSV-1 modified-live virus vaccinated pigs in response to HP-PRRSV-2 challenge

This study evaluated the immunomodulatory effect of quercetin on improving cross protection of porcine reproductive and respiratory syndrome virus-1 (PRRSV-1) modified-live virus (MLV) vaccine against highly pathogenic (HP)-PRRSV-2 challenge. Ex vivo experiments demonstrated that quercetin significantly enhanced type I interferon-regulated genes (IRGs) and type I and II interferon (IFN), and significantly decreased pro- and anti-inflammatory cytokine expressions in HP-PRRSV-inoculated monocyte-derived macrophages. In vivo experiments divided pigs (4-week-old; n = 24) into four groups of six pigs. Group 1 and group 2 were immunized with PRRSV-1 MLV vaccine at 0 dpv (day post vaccination). Group 2 also received oral administration of quercetin at 0–49 dpv. Group 3 was injected with PRRSV-1 MLV vaccine solvent at 0 dpv. Group 4 served as strict control. Group 1–3 were challenged intranasally with HP-PRRSV at 28 dpv and immune and clinical parameters were monitored weekly until 49 dpv. Group 1 demonstrated significantly reduced HP-PRRSV viremia, rectal temperature and clinical scores, and significantly improved average daily weight gain (ADWG), compared to group 3. Group 2 demonstrated significantly increased IFN regulatory factor 3, stimulator of IFN genes, IFNα, and significantly decreased transforming growth factor beta (TGFβ) mRNA expressions, compared to group 1. The animals demonstrated significantly reduced HP-PRRSV viremia, but did not demonstrate any further improved PRRSV-specific antibody responses, rectal temperature, clinical scores, and ADWG as compared to group 1. Our findings suggest that quercetin up-regulates IRGs, IFNα, and down-regulates TGFβ mRNA expressions which may contribute to further reducing number of viremic pigs and HP-PRRSV viremia which were conferred by PRRSV-1 MLV vaccine. Our findings also suggest that quercetin may serve as an effective oral immunomodulator for improving cell-mediated immune defense to HP-PRRSV.

A chitosan film containing quercetin-loaded transfersomes for treatment of secondary osteoporosis.

Osteoporosis, due to its prevalence worldwide, is a serious health problem. Topical administration of quercetin, a phytoestrogen, in the form of deformable transfersomes, could be used to treat osteoporosis to overcome its low oral solubility and bioavailability. Formulation process of transfersomes was screened by fractional factorial design and further optimized using full factorial design. Transfersomes showed good characteristics such as entrapment efficiency, particle size, zeta potential, and polydispersity index (83.0 ± 2.2%, 75.95 ± 2nm, - 13.6 ± 6mv and 0.333, respectively). Transfersomes were further loaded into chitosan film and showed good permeation through rat skin. Further, glucocorticoid-induced osteoporosis rat model showed induction of osteoporosis after day 30. On day 45, treatment with chitosan film containing quercetin-loaded transfersomes showed remarkable rise in femur thickness, length, density as well as in serum biochemical parameters such as calcium, phosphorous, alkaline phosphatase, and tartrate-resistant alkaline phosphatase compared to positive control group. Tensile strength of osteoporotic femur bone was also found to be increased and was comparable with normal group. Histomicrographic analysis of femur bone exhibited less disruptive and lytic changes. Thus, all the above findings indicated the beneficial effects of quercetin-loaded transfersome chitosan film, due to decline in osteoclastogenesis and osteoblast apoptosis, which further favored increase in osteoblast numbers and mineralization of bones. Thus, chitosan film containing quercetin-loaded transfersomes was found to be good alternative to oral administration of quercetin to treat osteoporosis, while easy applicability of film in the form of wrist band anytime, anywhere, and even at work achieve patient compliance. Graphical abstract.

The protective effect of quercetin on retinal inflammation in mice: the involvement of tumor necrosis factor/nuclear factor-κB signaling pathways.

Quercetin is a natural flavonoid that occurs in fruits and vegetables. Retinal inflammation is an important cause of vision loss. This study was aimed to analyze the effects of oral administration of quercetin on retinal inflammation. Transgenic mice, carrying nuclear factor-κB (NF-κB)-driven luciferase genes, were injected with 1 mg per kg body weight of lipopolysaccharide (LPS). Various amounts (1, 10, and 100 mg per kg body weight) of quercetin were orally given to mice. LPS-induced retinal inflammation was evaluated by bioluminescence imaging and histological examination 4 hours later. RNA-Seq analysis of gene expression profiles was performed to explain the mechanisms of quercetin on eye inflammation. Our data showed that LPS enhanced luminescent signals on ocular tissues, while LPS-induced luminescence intensities were significantly suppressed by quercetin by 73.61 ± 21.74%. LPS significantly increased the thickness of retinal tissues by 1.52 ± 0.37 fold, in comparison with the mock, while quercetin reduced the LPS-induced retinal thickness and decreased the accumulation of infiltrating granulocytes. Biological pathway analysis showed that tumor necrosis factor (TNF), cytokine, and NF-κB signaling pathways were involved in the anti-inflammatory mechanisms of quercetin. Immunohistochemical staining further showed that quercetin reduced the activation of NF-κB, the expression of interleukin-1β and TNF-α, and the infiltration of granulocytes in retinal tissues. In conclusion, this is the first study reporting the effects and mechanisms of orally administered quercetin against LPS-induced retinal inflammation in mice. Due to its safety, our study suggested that supplementation of quercetin has beneficial effects on the eyes.

Quercetin modulates hyperglycemia by improving the pancreatic antioxidant status and enzymes activities linked with glucose metabolism in type 2 diabetes model of rats: In silico studies of molecular interaction of quercetin with hexokinase and catalase.

Quercetin was assessed for its antihyperglycemic effect in fructose-streptozotocin (STZ) induced diabetic rats. The oral administration of quercetin at the dosage of 25 and 50mg/kg for 28days remarkably reduced the level of blood glucose, glycosylated hemoglobin (Hb), and hepatic glycogen but enhanced plasma Hb concentration. The altered activities of glucose-6-phosphatase and hexokinase in diabetic rats were significantly improved upon quercetin treatment. Furthermore, the antioxidant activity of pancreatic superoxide dismutase, catalase (CAT), and reduced glutathione was effectively increased while the value for thiobarbituric acid reactive species was decreased. A significant reduction of glycemia was observed in the glucose tolerance test, 120min after the glucose pulse. Also, the damage caused by fructose-STZ in the liver and pancreas of diabetic animals were restored to near normal. Molecular docking of quercetin showed a high affinity for hexokinase and CAT with a binding energy of -7.82 and -9.83kcal/mol, respectively, more elevated than the standard drugs. PRACTICAL APPLICATIONS: Functional foods and nutraceuticals have increasingly interested the consumers in terms of health benefits and have started focussing on the prevention or cure of disease by the foods and their health-enhancing phytochemicals. Quercetin is one of the most potent naturally occurring antioxidants within the flavonoid subclasses, mostly distributed as a secondary metabolite in fruits, vegetables, and black tea. Based on the results exhibited in the present study, we proposed that the consumption of foods rich in quercetin could be a cheap and affordable nutraceutical that can be developed for the treatment of T2DM and its complications. Further studies on the safety aspects of quercetin in long-term usage are strongly recommended before implementing for the treatment of human diseases.

Quercetin reduces atherosclerotic lesions by altering the gut microbiota and reducing atherogenic lipid metabolites

Epidemiological studies have correlated cardiovascular disease and atherosclerosis with lifestyle factors such as sedentary behaviour and a high-calorie diet. Recent studies of pathogenesis have highlighted the significance of the intestinal microbiota and chronic inflammation with respect to both the onset and development of atherosclerosis. This study examined the hypothesis that the oral administration of quercetin to low-density lipoprotein receptor-null (Ldlr-/- ) mice would improve gut health by altering the gut microbiota and controlling the levels of atherogenic lipid metabolites and proinflammatory mediators in the intestine and serum. Mice were maintained on a high-fat diet with or without oral quercetin administration for 12weeks. Quercetin treatment suppressed body weight gains and reduced the extent of atherosclerotic lesions in the aortic sinus. Reduced malondialdehyde and increased interleukin 6 levels further indicated the protective effect of quercetin against immune/inflammatory responses and oxidative stress. Furthermore, quercetin led to decreased intestinal levels of cholesterol, lysophosphatidic acids and atherogenic lysophosphatidylcholine (LPC 18:1) and an increased level of coprostanol. A phylum-level microbial analysis revealed that quercetin treatment reduced the abundance of Verrocomicrobia and increased microbiome diversity and the abundances of Actinobacteria, Cyanobacteria and Firmicutes. A Spearman analysis revealed negative correlations of Actinobacteria with intestinal and plasma LPC 18:1 and caecal cholesterol levels and of Firmicutes and Cyanobacteria with the plasma LPC 18:1 level. This study demonstrated the ability of quercetin treatment to reduce lipid levels, as well as the areas of atherosclerotic lesions and sizes of plaques. This treatment also altered the composition of the gut microbiota and decreased the levels of atherogenic lipid metabolites. Oral quercetin treatment may represent a new approach to mitigating the onset and development of atherosclerosis.

Quercetin‐Induced miR‐369‐3p Suppresses Chronic Inflammatory Response Targeting C/EBP‐β

Dendritic cells (DCs) are the most potent antigen-presenting cells that play an important role in the crosstalk between the innate and the adaptive immune response. Quercetin exposure is identified as an effective strategy to suppress the inflammatory response induced by LPS. In this study, using a next-generation sequencing analysis, the effect of quercetin on microRNAs (miRNAs) expression in DCs is examined. A signature of 113 miRNAs that are differentially regulated in LPS-stimulated DCs after quercetin exposure is defined. It is demonstrated that the loss of function of miR-369-3p in LPS-stimulated DCs during quercetin exposure led to an increase of CCAAT/enhancer binding protein β (C/EBP-β) mRNA and protein and its downstream targets tumor necrosis factor-α (TNF-α) and interleukin 6 (IL6). Conversely, it is shown that the ectopic induction of miR-369-3p without quercetin suppresses the inflammatory response of LPS reducing C/EBP-β, TNF-α, and IL6 production. In vivo, oral administration of quercetin in dextran-sulfate-sodium-induced colitis induces miR-369-3p expression. These findings indicate that quercetin-induced miR-369-3p regulates the inflammatory cascade in chronic inflammatory response and present promising therapeutic implications.

Preventive Effect of Quercetin in a Triple Transgenic Alzheimer's Disease Mice Model.

Alzheimer’s disease (AD) is the most common type of dementia and is the leading cause of disability in elderly people worldwide. Current pharmacological therapies do not cure the disease, and for this reason, some pharmacotherapy studies have investigated preventive treatments focused on modifiable nutritional factors such as diet. Quercetin (Qc) is a flavonoid found in fruits and vegetables that has several biological properties. In this study, we evaluated the effect of chronic oral quercetin administration (100 mg/kg) on neurodegeneration markers and cognitive and emotional deficits in a triple transgenic Alzheimer’s disease (3xTg-AD) mouse model using histological and behavioral analyses. Our results suggest that long-term (12 months) oral preventive treatment with quercetin has significant effects on β-amyloidosis reduction and tends to decrease tauopathy in the hippocampus and amygdala. These decreases positively affected the cognitive functional recovery (without modifying the emotional skills) of 3xTg-AD mice. These findings suggest that preventive and chronic administration of Qc might help to delay the development of histopathological hallmarks and cognitive function deficits in AD.