quercetin-3-o-glucuronide and 3-methylquercetin

quercetin-3-o-glucuronide has been researched along with 3-methylquercetin* in 12 studies

Trials

1 trial(s) available for quercetin-3-o-glucuronide and 3-methylquercetin

ArticleYear
The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: correlation with beta-glucuronidase activity.
    Pharmacological research, 2014, Volume: 89

    Quercetin exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in hypertensive humans and animal models. We hypothesized that oral quercetin might induce vasodilator effects in humans and that they might be related to the deconjugation of quercetin-3-O-glucuronide (Q3GA).. double blind, randomized, placebo-controlled trial. Fifteen healthy volunteers (26±5 years, 6 female) were given a capsule containing placebo, 200 or 400mg of quercetin in random order in three consecutive weeks. At 2h a dose-dependent increase in Q3GA was observed in plasma (∼0.4 and 1μM for 200 and 400mg, respectively) with minor levels of quercetin and isorhamnetin. No changes were observed in blood pressure. At 5h quercetin induced and increase in brachial arterial diameter that correlated with the product of the levels of Q3GA by the plasma glucuronidase activity. There was an increase in urinary levels of glutathione but there was no increase in nitrites plus nitrates. Quercetin and isorhamnetin also relaxed human umbilical arteries in vitro while Q3GA was without effect. In conclusions, quercetin exerts acute vasodilator effects in vivo in normotensive, normocholesterolemic human subjects. These results are consistent with the effects being due to the deconjugation of the metabolite Q3GA.

    Topics: Adult; Blood Pressure; Brachial Artery; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glucuronidase; Glutathione; Healthy Volunteers; Hemodynamics; Humans; Male; Nitrates; Nitrites; Quercetin; Umbilical Arteries; Vasodilator Agents; Young Adult

2014

Other Studies

11 other study(ies) available for quercetin-3-o-glucuronide and 3-methylquercetin

ArticleYear
Identification of compound causing yellow bone discoloration following alpha-glycosyl isoquercitrin exposure in Sprague-Dawley rats.
    Archives of toxicology, 2020, Volume: 94, Issue:7

    Previous rat toxicity studies of alpha-glycosyl isoquercitrin (AGIQ), a water-soluble flavonol glycoside derived from rutin, revealed systemic yellow bone discoloration. This investigative study was conducted to determine the AGIQ metabolite(s) responsible for the discoloration. Female Sprague-Dawley rats were administered dietary AGIQ at doses of 0%, 1.5%, 3.0%, or 5.0% (0, 1735.0, 3480.8, and 5873.7 mg/kg/day, respectively) for 14 days, followed by a 14- or 28-day recovery period. Measurements of quercetin in urine and quercetin, quercetin 3-O-glucuronide, kaempferol, and 3-o-methylquercetin metabolites of AGIQ in bone (femur), white and brown fat, and cerebrum samples were conducted following the exposure period and each recovery period. Gross examination of the femur revealed yellow discoloration that increased in intensity with dose and was still present in a dose-related manner following both recovery periods. Quercetin, at levels correlating with AGIQ dose, was measured in the urine following the 14-day exposure period and, at lower concentrations, 14 or 28 days following cessation of AGIQ exposure. All four metabolites were present in a dose-dependent manner in the femur following 14 days of dietary exposure; only quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were present during the recovery periods. Quercetin, quercetin 3-O-glucuronide, and 3-o-methylquercetin were detected in white fat (along with kaempferol), brown fat (excluding quercetin due to analytical interference), and cerebrum samples, indicating systemic availability of the metabolites. Collectively, these data implicate quercetin, quercetin 3-O-glucuronide, or 3-o-methylquercetin (or a combination thereof) as the most likely metabolite of AGIQ causing the yellow discoloration of bone in rats administered dietary AGIQ.

    Topics: Animals; Biotransformation; Female; Femur; Pigmentation; Pigmentation Disorders; Quercetin; Rats, Sprague-Dawley; Time Factors

2020
Effects of Quercetin Metabolites on Triglyceride Metabolism of 3T3-L1 Preadipocytes and Mature Adipocytes.
    International journal of molecular sciences, 2019, Jan-11, Volume: 20, Issue:2

    Quercetin (Q) has rapid metabolism, which may make it worthwhile to focus on the potential activity of its metabolites. Our aim was to evaluate the triglyceride-lowering effects of Q metabolites in mature and pre-adipocytes, and to compare them to those induced by Q. 3T3-L1 mature and pre-adipocytes were treated with 0.1, 1 and 10 µM of Q, tamarixetin (TAM), isorhamnetin (ISO), quercetin-3-

    Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Differentiation; Disaccharides; Dose-Response Relationship, Drug; Fatty Acids, Nonesterified; Gene Expression Profiling; Gene Expression Regulation; Glycerol; Lipid Metabolism; Mice; Quercetin; Triglycerides

2019
Cardioprotective and cardiotoxic effects of quercetin and two of its in vivo metabolites on differentiated h9c2 cardiomyocytes.
    Basic & clinical pharmacology & toxicology, 2015, Volume: 116, Issue:2

    Whilst mitotic rat embryonic cardiomyoblast-derived H9c2 cells have been widely used as a model system to study the protective mechanisms associated with flavonoids, they are not fully differentiated cardiac cells. Hence, the aim of this study was to investigate the cardioprotective and cardiotoxic actions of quercetin and two of its major in vivo metabolites, quercetin 3-glucuronide and 3'-O-methyl quercetin, using differentiated H9c2 cells. The differentiated cardiomyocyte-like phenotype was confirmed by monitoring expression of cardiac troponin 1 after 7 days of culture in reduced serum medium containing 10 nM all-trans retinoic acid. Quercetin-induced cardiotoxicity was assessed by monitoring MTT reduction, lactate dehydrogenase (LDH) release, caspase 3 activity and reactive oxygen species production after prolonged flavonoid exposure (72 hr). Cardiotoxicity was observed with quercetin and 3'-O-methyl quercetin, but not quercetin 3-glucuronide. Cardioprotection was assessed by pre-treating differentiated H9c2 cells with quercetin or its metabolites for 24 hr prior to 2-hr exposure to 600 μM H2 O2, after which oxidative stress-induced cell damage was assessed by measuring MTT reduction and LDH release. Cardioprotection was observed with quercetin and 3'-O-methyl quercetin, but not with quercetin 3-glucuronide. Quercetin attenuated H2 O2 -induced activation of ERK1/2, PKB, p38 MAPK and JNK, but inhibitors of these kinases did not modulate quercetin-induced protection or H2 O2 -induced cell death. In summary, quercetin triggers cardioprotection against oxidative stress-induced cell death and cardiotoxicity after prolonged exposure. Further studies are required to investigate the complex interplay between the numerous signalling pathways that are modulated by quercetin and which may contribute to the cardioprotective and cardiotoxic effects of this important flavonoid.

    Topics: Animals; Cardiotonic Agents; Cell Death; Cell Differentiation; Cell Line; Hydrogen Peroxide; Myocytes, Cardiac; Oxidative Stress; Quercetin; Rats; Reactive Oxygen Species; Signal Transduction

2015
Quercetin and its metabolites inhibit the membrane NADPH oxidase activity in vascular smooth muscle cells from normotensive and spontaneously hypertensive rats.
    Food & function, 2015, Volume: 6, Issue:2

    Quercetin, the most abundant dietary flavonol, exerts antioxidant effects reducing vascular superoxide (O2(-)) and improving endothelial function in animal models of cardiovascular disease. Herein we evaluated the effects of quercetin, and its plasma metabolites, on the nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase activity, the main source of O2(-) in the vessel wall, in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Quercetin and its metabolites isorhamnetin and kaempferol inhibited the NADPH-stimulated lucigenin-chemiluminescence signal in VSMCs from both strains. The inhibitory effect of quercetin-3-glucuronide increased after prolonged incubation and was inhibited in the presence of the β-glucuronidase inhibitor saccharolactone. These effects were unrelated to their O2(-) scavenging properties, since they induced only a small inhibition of the rate of pyrogallol autoxidation at high concentrations. All bioflavonoids tested acted as non-competitive inhibitors with respect to NADPH. In conclusion, quercetin and its metabolites inhibit the NADPH oxidase activity in VSMCs reducing O2(-) generation more efficiently than their effect as O2(-) scavengers. The effect of quercetin-3-glucuronide was due to deconjugation and release of free quercetin. The effect is similar in VSMCs from normotensive and hypertensive animals.

    Topics: Animals; Antihypertensive Agents; Antioxidants; Cells, Cultured; Glucuronidase; Glycoproteins; Kaempferols; Male; Muscle, Smooth, Vascular; NADPH Oxidases; Quercetin; Rats; Rats, Inbred SHR; Rats, Inbred WKY

2015
Quercetin Metabolites Up-Regulate the Antioxidant Response in Osteoblasts Isolated From Fetal Rat Calvaria.
    Journal of cellular biochemistry, 2015, Volume: 116, Issue:9

    Oxidative stress contributes to osteoporosis by suppressing differentiation of osteoblasts, suggesting the osteoblast antioxidant response may be a viable strategy for osteoporosis prevention. Quercetin, an antioxidant flavonol, up-regulates the antioxidant response in many cell types, but studies are needed to understand the effects of quercetin plasma metabolites on the osteoblast antioxidant response. The first specific aim was to examine antioxidant response genes and proteins in osteoblasts exposed to plasma quercetin metabolites. The second specific aim was to identify potential signaling pathways in the osteoblast antioxidant response that mediate the effect of quercetin, specifically Nrf2, ERK1/2, and NFκB p65. Osteoblasts isolated from fetal rat calvaria were treated with doses up to 20 μM of three different quercetin metabolites found in blood plasma after consumption of quercetin-rich foods or supplements: quercetin aglycone (QRC), isorhamnetin (ISO), or quercetin 3-O-glucuronide (Q3G). Alternatively, some cells received a 2:1:1 mixture of all three metabolites (10 μM Q3G: 5 μM ISO: 5 μM QRC) to evaluate synergistic effects. Antioxidant response genes and proteins known to be up-regulated by quercetin were analyzed along with Nrf2, ERK1/2, and NFκB proteins. Both QRC and ISO, but not Q3G, up-regulated heme oxygenase-1 (HO-1) and γ-glutamate cysteine ligase catalytic subunit (GCLC) at the mRNA and protein level. Synergistic effects of metabolites were not observed. Up-regulation of HO-1 and GCLC was associated with suppression of phosphorylated ERK1/2 and NFκB, but no alterations in Nrf2 protein levels were observed. This study shows that the antioxidant response of osteoblasts is differentially stimulated by quercetin metabolites.

    Topics: Animals; Antioxidants; Cells, Cultured; Osteoblasts; Phosphorylation; Quercetin; Rats; Signal Transduction; Skull; Up-Regulation

2015
Interference of flavonoids with enzymatic assays for the determination of free fatty acid and triglyceride levels.
    Analytical and bioanalytical chemistry, 2012, Volume: 402, Issue:3

    Flavonoids are bioactive food compounds with potential lipid-lowering effects. Commercially available enzymatic assays are widely used to determine free fatty acid (FFA) and triglyceride (TG) levels both in vivo in plasma or serum and in vitro in cell culture medium or cell lysate. However, we have observed that various flavonoids interfere with peroxidases used in these enzymatic assays, resulting in incorrect lower FFA and TG levels than actually present. Furthermore, addition of isorhamnetin or the major metabolite of the flavonoid quercetin in human and rat plasma, quercetin-3-O-glucuronide, to murine serum also resulted in a significant reduction of the detected TG levels, while a trend was seen for FFA levels. It is concluded that when applying these assays, vigilance is needed and alternative analytical methods, directly assessing FFA or TG levels, should be used for studying the biological effects of flavonoids on FFA and TG levels.

    Topics: Analysis of Variance; Animals; Biochemistry; Culture Media; Fatty Acids, Nonesterified; Flavonoids; Humans; Male; Mice; Mice, Inbred C57BL; Peroxidases; Quercetin; Rats; Triglycerides

2012
Effects of physiological quercetin metabolites on interleukin-1β-induced inducible NOS expression.
    The Journal of nutritional biochemistry, 2012, Volume: 23, Issue:11

    Cytokines released by inflammatory cells around the pancreatic islets are implicated in the pathogenesis of diabetes mellitus. Specifically, interleukin-1β (IL-1β) is known to be involved in islet β-cell damage by activation of nuclear factor-κB (NF-κB)-mediated inducible nitric oxide synthase (iNOS) gene expression. Though most flavonoids are shown to have various beneficial effects, little is known about the anti-inflammatory effects of their metabolites. Therefore, we investigated the effects of quercetin and its metabolites quercetin 3'-sulfate, quercetin 3-glucuronide and isorhamnetin 3-glucuronide on IL-1β-stimulated iNOS gene expression in RINm5F β-cells. The nitrite level, iNOS protein and its mRNA expression levels and iNOS promoter activity were measured. In addition, IκBα protein phosphorylation, nuclear translocation of nuclear factor-κB (NF-κB) and NF-κB DNA binding activity were determined. Adenosine 5'-triphosphate disodium salt-induced insulin release was also measured. Quercetin significantly reduced IL-1β-induced nitrite production, iNOS protein and its mRNA expression levels, and it also inhibited IL-1β-induced IκBα phosphorylation, NF-κB activation and iNOS promoter activity. Additionally, quercetin significantly restored the inhibition of insulin secretion by IL-1β. Meanwhile, quercetin metabolites did not show any effect on IL-1β-induced iNOS gene expression and also on insulin secretion. Therefore, in terms of iNOS expression mechanism, dietary ingestion of quercetin is unlikely to show anti-inflammatory effects in rat islet β-cells exposed to IL-1β.

    Topics: Animals; Cells, Cultured; Gene Expression Regulation, Enzymologic; I-kappa B Proteins; Insulin; Insulin Secretion; Interleukin-1beta; Islets of Langerhans; NF-kappa B; Nitric Oxide Synthase Type II; Nitrites; Phosphorylation; Promoter Regions, Genetic; Quercetin; Rats

2012
Effect of quercetin and its metabolites isorhamnetin and quercetin-3-glucuronide on inflammatory gene expression: role of miR-155.
    The Journal of nutritional biochemistry, 2011, Volume: 22, Issue:3

    In the present study the effect of quercetin and its major metabolites quercetin-3-glucuronide (Q3G) and isorhamnetin on inflammatory gene expression was determined in murine RAW264.7 macrophages stimulated with lipopolysaccharide. Quercetin and isorhamnetin but not Q3G significantly decreased mRNA and protein levels of tumor necrosis factor alpha. Furthermore a significant decrease in mRNA levels of interleukin 1β, interleukin 6, macrophage inflammatory protein 1α and inducible nitric oxide synthase was evident in response to the quercetin treatment. However Q3G did not affect inflammatory gene expression. Anti-inflammatory properties of quercetin and isorhamnetin were accompanied by an increase in heme oxygenase 1 protein levels, a downstream target of the transcription factor Nrf2, known to antagonize chronic inflammation. Furthermore, proinflammatory microRNA-155 was down-regulated by quercetin and isorhamnetin but not by Q3G. Finally, anti-inflammatory properties of quercetin were confirmed in vivo in mice fed quercetin-enriched diets (0.1 mg quercetin/g diet) over 6 weeks.

    Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cell Survival; Down-Regulation; Female; Flavonols; Gene Expression; Heme Oxygenase-1; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred C57BL; MicroRNAs; Nitric Oxide Synthase Type II; Quercetin; Tumor Necrosis Factor-alpha

2011
Glucuronidated and sulfated metabolites of the flavonoid quercetin prevent endothelial dysfunction but lack direct vasorelaxant effects in rat aorta.
    Atherosclerosis, 2009, Volume: 204, Issue:1

    Epidemiological studies have reported an inverse association between dietary flavonoid intake and mortality for ischemic heart disease. Quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, but it is rapidly metabolized during absorption by methylation, glucuronidation and sulfation. We have analyzed the vasorelaxant effects and the role on NO bioavailability and endothelial function of quercetin and its conjugated metabolites (quercetin-3-glucuronide, isorhamnetin-3-glucuronide and quercetin-3'-sulfate) in rat aorta. Thoracic aortic rings isolated from Wistar rats were mounted for isometric force recording and endothelial function was tested by measuring the vasorelaxant response to acetylcholine. NADPH-enhanced O(2)(-) release was quantified in homogenates from cultured aortic smooth muscle cells using lucigenin chemiluminescence. Unlike quercetin, the conjugated metabolites had no direct vasorelaxant effect, and did not modify endothelial function or the biological activity of NO. However, all metabolites (at 10 micromol/L) prevented, at least partially, the impairment of endothelial-derived NO response under conditions of high oxidative stress induced by the SOD inhibitor DETCA. Furthermore, they protected the biological activity of exogenous NO when impaired by DETCA. Quercetin and quercetin-3'-sulfate (>or=10 micromol/L) or quercetin-3-glucuronide (100 micromol/L) inhibited NADPH oxidase-derived O(2)(-) release. Quercetin and quercetin-3-glucuronide (1 micromol/L) prevented the endothelial dysfunction induced by incubation with ET-1. These data indicate, for the first time, that the conjugated metabolites could be responsible for the in vivo protective activity of quercetin on endothelial dysfunction.

    Topics: Acetylcholine; Animals; Antioxidants; Aorta, Thoracic; Biotransformation; Dose-Response Relationship, Drug; Endothelin-1; Endothelium, Vascular; Flavonols; Glucuronides; In Vitro Techniques; NADPH Oxidases; Nitric Oxide; Oxidative Stress; Quercetin; Rats; Rats, Wistar; Sulfates; Superoxides; Vasodilation; Vasodilator Agents

2009
[HPLC-MS analysis of quercetin and its metabolites in portal vein after intragastrical administration of quercetin in rats].
    Wei sheng yan jiu = Journal of hygiene research, 2009, Volume: 38, Issue:4

    To analyse the plasma contents of querceitn and its metabolites in portal vein in rats.. Male Wistar rats were orally administrated with quercetin at the dose of 40 mg/kg. The blood samples were corrected from the portal vein 1 h later. The quercetin and its metabolites in plasma were analysed with high performance liquid chromatography-mass spetrometry (HPLC-MS) method.. The quercetin, quercetin-3-glucuronide, quercetin glucuronide sulfate, 3'-O-methylated quercetin, 4'-O- methylated quercetin and quercetin sulfate were detected in portal vein.. The results indicated that the quercetin was extensively metabolized in intestine and entered the portal vein in various forms after administration.

    Topics: Administration, Oral; Animals; Antioxidants; Chromatography, High Pressure Liquid; Male; Mass Spectrometry; Portal Vein; Quercetin; Random Allocation; Rats; Rats, Wistar

2009
Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells.
    Atherosclerosis, 2009, Volume: 202, Issue:2

    Dietary flavonoids have been shown to have a number of anti-inflammatory properties, including decreasing the expression of adhesion molecules. Flavonoids however, are metabolised during absorption and the forms reaching the systemic circulation are glucuronidated, sulfated and methylated. Most previous studies of the effects of flavonoids have used the parent compounds rather than the metabolites found in blood plasma and we have recently shown that metabolites of quercetin can retain some of the anti-inflammatory properties of the parent aglycone when used to treat human umbilical endothelial cells (HUVEC). Using both physiologically achievable (2 microM) and supraphysiological (10 microM) concentrations, we investigated the ability of quercetin and its predominant human metabolites to attenuate the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) in human umbilical artery smooth muscle cells (HUASMC) activated by tumor necrosis factor-alpha (TNFalpha). Quercetin was able to reduce TNFalpha-induced upregulation of VCAM-1, ICAM-1 and MCP-1 at both the protein and transcript (mRNA) level in HUASMC. However the quercetin metabolites, quercetin 3'-sulfate, quercetin 3-glucuronide and 3'-methylquercetin 3-glucuronide, had no effect on TNFalpha-induced up regulation of adhesion molecule or chemokine expression, at either concentration tested. These data do not support the notion that the vascular anti-inflammatory effects of quercetin consumption are mediated through effects on smooth muscle cells.

    Topics: Cell Division; Cell Survival; Cells, Cultured; Chemokine CCL2; Chemokines; Flavonols; Gene Expression; Humans; Intercellular Adhesion Molecule-1; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Quercetin; RNA, Messenger; Tumor Necrosis Factor-alpha; Umbilical Arteries; Vascular Cell Adhesion Molecule-1

2009