Identification of quercetin 3- O -β-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin

Moon, Jae‐Hak; Tsushida, Tojiro; Nakahara, Kazuhiko; Terao, Junji

doi:10.1016/s0891-5849(01)00522-6

Cited by 255 publications

(189 citation statements)

References 33 publications

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“…Thus, the own biological activity of the glucuronides should be considered, even though the possibility of hydrolysis into aglycones inside the cells is still under investigation (O'Leary et al, 2001;Shimoi et al, 2001). A few studies have reported antioxidative or anti-inflammatory activity of flavonoid conjugates (Manach et al, 1998;Hiermann et al, 1998;Day et al, 2000;Moon et al, 2001). The intestinal microflora, besides the deglycosylation of narirutin and hesperidin, has also the capacity to degrade the aglycones into phenolic acids such as p-hydroxyphenylpropionic, p-coumaric, and p-hydroxybenzoic acids (Booth et al, 1958;Scheline, 1991;Felgines et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

Manach¹,

Morand²,

et al. 2003

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Objective: Flavanones are polyphenols specific of citrus fruits, where they are present in high amounts. Although citrus fruits and juices are widely consumed in the world, little information has been published on flavanone bioavailability in humans. The aim of the present study was to determine the nature of the circulating metabolites, the plasma kinetics and the urinary excretion patterns of the flavanones, hesperidin and narirutin. Design: After an overnight fast, five healthy volunteers ingested 0.5 or 1 l of a commercial orange juice providing 444 mg=l hesperidin and 96.4 mg=l narirutin, together with a polyphenol-free breakfast. Blood was sampled at 10 different timepoints over a 24 h period. Urine was collected for 48 h, in five fractions. Results: Flavanones metabolites appeared in plasma 3 h after the juice ingestion, reached a peak between 5 and 7 h, then returned to baseline at 24 h. The peak plasma concentration of hesperetin was 0.46 AE 0.07 mmol=l and 1.28 AE 0.13 mmol=l after the 0.5 and 1 l intake, respectively. It was lower for naringenin: 0.20 AE 0.04 mmol=l after the 1 l dose. The circulating forms of hesperetin were glucuronides (87%) and sulphoglucuronides (13%). For both flavanones, the urinary excretion was nearly complete 24 h after the orange juice ingestion. The relative urinary excretion was similar for hesperetin and naringenin and did not depend on the dose: values ranged from 4.1 AE 1.2 to 7.9 AE 1.7% of the intake. Conclusions: In case of a moderate or high consumption of orange juice, flavanones may represent an important part of the pool of total polyphenols present in plasma.

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Section: Discussionmentioning

confidence: 99%

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

Manach¹,

Morand²,

et al. 2003

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“…Only a very few investigators have studied the influence of metabolism on the bioactivity of flavonoids [105,137,178,193,194], thus most of the effects reported based on in vitro experiments, cannot be extrapolated to in vivo situations. For example, one of the most intensively investigated flavonoids, quercetin, is often just used as the aglycone in cell culture systems and interesting biological activities such as modulation of the multidrug-resistance protein [118], induction of apoptosis [168], inhibition of the expression of nitric oxide synthase and cyclooxygenase [162], protection against oxidative stress [88] and modulation of the calcium homeostasis [209] have been reported.…”

Section: Flavonoids: Neuroprotective Agents In Vivo and In Vitro?mentioning

confidence: 99%

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

308

178

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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“…Previous reports have clearly indicated that quercetin-3-glucuronide (Q3GA) and quercetin-3 0 -sulfate are the major quercetin conjugates in rat and human plasma, while aglycone was not detected. [23][24][25] Typical profiles of quercetin metabolites and aglycones in human plasma before and after intake of onion are shown in Fig. 1B.…”

Section: Bioavailability Of Polyphenols and Their Activitymentioning

confidence: 99%

“…Although the biological activities of flavonoids are generally attenuated after conversion to their metabolites, the potent activities of various quercetin metabolites associated with oxidative stress have been reported. 27) It is expected that Q3GA represents the radical scavenging actions of quercetin metabolites in vivo, 24) because even after enzymatic metabolization, it retains the catechol moiety (3 0 ,4 0 -o-dihydroxyl group) responsible for the radicalscavenging ability of quercetin. In contrast to the fact that no quercetin aglycone was detected in human plasma, tea catechins, especially ECg and EGCg, were detected as aglycones (at 20 and 60 ng/mL respectively, at maximum concentrations 1-2 h after ingestion) in human plasma after the intake of green tea.…”

Section: Bioavailability Of Polyphenols and Their Activitymentioning

confidence: 99%

“…[36][37][38][39] In most cases, to prepare immunogens, haptens or analogous derivatives were coupled with carrier proteins such as keyhole limpet hemocyanin (KLH), bovine serum albumin (BSA), or ovalbumin through amide-bond formation using carbodiimide reagents. To prepare anti-polyphenol antibodies, we utilized chemically synthesized Q3GA 24) as the immunogen, because (i) glucuronide metabolites are the most abundant forms of quercetin 23,24) and other polyphenols in vivo, and (ii) glucuronide metabolites have one carboxyl group in their intact structures available for coupling with carrier proteins. For catechins, because we did not prepare authentic catechin glucuronides, (À)-epicatechin (EC), which contains a backbone structure common to four major tea catechins,…”

Section: Anti-polyphenol Monoclonal Antibodiesmentioning

confidence: 99%

See 1 more Smart Citation

Immunochemical Detection of Food-Derived Polyphenols in the Aorta: Macrophages as a Major Target Underlying the Anti-Atherosclerotic Activity of Polyphenols

Kawai

2011

Bioscience, Biotechnology, and Biochemistry

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Identification of quercetin 3- O -β-D-glucuronide as an antioxidative metabolite in rat plasma after oral administration of quercetin

Cited by 255 publications

References 33 publications

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

Bioavailability in humans of the flavanones hesperidin and narirutin after the ingestion of two doses of orange juice

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Immunochemical Detection of Food-Derived Polyphenols in the Aorta: Macrophages as a Major Target Underlying the Anti-Atherosclerotic Activity of Polyphenols

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