Protection by quercetin and quercetin 3-<i>O</i>-β-<scp>D</scp>-glucuronide of peroxynitrite-induced antioxidant consumption in human plasma low-density lipoprotein

Terao, Junji; Yamaguchi, Sachiyo; Shirai, Mutsuko; Miyoshi, Mariko; Moon, Jae‐Hak; Oshima, Shuzo; Inakuma, Takahiro; Tsushida, Tojiro; Kato, Yoji

doi:10.1080/10715760100301421

Cited by 62 publications

(38 citation statements)

References 34 publications

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“…The aglycone was then reconjugated by UDP-glucuronosyltransferase in the small intestine or liver (Day et al, 2000a;Oliveira & Watson, 2000). Quercetin-3-glucuronide retained the ability of quercetin to inhibit LDL oxidation Terao et al, 2001), but further work is required to determine the effect of conjugation on bioactivity of kaempferol-3-glucuronide. A single kaempferol mono-sulphate was tentatively identified by selected ion monitoring LC/MS, which, based on evidence from metabolism of kaempferol by human hepatocytes , is likely to be kaempferol-7-sulphate.…”

Section: Discussionmentioning

confidence: 99%

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

et al. 2004

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Objective: To determine the absorption, excretion and metabolism of kaempferol in humans. Design: A pharmacokinetic study of kaempferol from endive over 24 h. Subjects: Four healthy males and four healthy females. Results: Kaempferol, from a relatively low dose (9 mg), was absorbed from endive with a mean maximum plasma concentration of 0.1 mM, at a time of 5.8 h, indicating absorption from the distal section of the small intestine and/or the colon. Although a 7.5-fold interindividual variation between the highest and lowest maximum plasma concentration was observed, most individuals showed remarkably consistent pharmacokinetic profiles. This contrasts with profiles for other flavonoids that are absorbed predominantly from the large intestine (eg rutin). An average of 1.9% of the kaempferol dose was excreted in 24 h. Most subjects also showed an early absorption peak, probably corresponding to kaempferol-3-glucoside, present at a level of 14% in the endive. Kaempferol-3-glucuronide was the major compound detected in plasma and urine. Quercetin was not detected in plasma or urine indicating a lack of phase I hydroxylation of kaempferol. Conclusions: Kaempferol is absorbed more efficiently than quercetin in humans even at low oral doses. The predominant form in plasma is a 3-glucuronide conjugate, and interindividual variation in absorption and excretion is low, suggesting that urinary kaempferol could be used as a biomarker for exposure. Sponsorship: Biotechnology and Biological Sciences Research council for core strategic funding and the University of Leeds for a departmental fellowship (AJD).

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Section: Discussionmentioning

confidence: 99%

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

et al. 2004

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“…Furthermore, NOS-II has also been found in macrophages in multiple sclerosis plaques (8) and in the brain lesions of mice chronically infected with T. b. brucei (15). Quercetin has already been shown to offer protection from peroxynitriteinduced consumption of endogenous lycopene beta-carotene and alpha-tocopherol (30).…”

Section: Discussionmentioning

confidence: 99%

Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages

Mamani-Matsuda¹,

Rambert²,

Malvy

et al. 2004

Antimicrob Agents Chemother

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In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-␣ and nitric oxide derivatives. In the present study, quercetin (3,3,4,5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-␣ and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.Human African trypanosomiasis (HAT), or sleeping sickness, is provoked by the inoculation of Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense into humans by a tse-tse fly. HAT is considered a reemerging disease, mainly due to the deterioration of health facilities in endemic areas. Blood monocytes and tissue macrophages play a key role in the control of parasite numbers, and an increased number of activated hematopoietic cells are observed during trypanosomiasis (33). Trypanosome-derived products were also shown to activate the generation by macrophages of various proinflammatory mediators including tumor necrosis factor alpha (TNF-␣), nitric oxide (NO), and interleukin-1 (IL-1) (7,19,28). TNF-␣ and NO fulfill important functions in host-parasite interactions as they control infections by various pathogens, including T. b. gambiense (6,21,32). In addition, chronic secretion of macrophage-derived mediators is in part responsible for the pathogenic aspects of HAT (18,20,25,27). Accordingly, a correlation can be made between high levels in serum of TNF-␣ and disease severity in HAT (25), and successful treatment with melarsoprol significantly reduced the circulating concentration of this cytokine in HAT patients (27).Only a few drugs are available to treat HAT, and some of them are effective only during the first phase of disease or are difficult to administer because of their high toxicity. These facts led us to investigate the effects of nutrition-derived flavonoids on in vitro interactions between T. b. gambiense and human leukocytes. Flavonoids are produced in plants in response to environmental stress such as adverse weather or attacks by insects, animals, or pathogens (37). For humans, the main flavonoid dietary sources are fruits, beverages, vegetables, dry legumes, and cereals. Recently, various purified polyphenolic compounds were defined as strong free-radical scavenging agents that display antitumoral, antimicrobial, and anti-inflammatory activities (3).Quercetin and its derivatives are among the most common polyphenolic flavonoids present in plants such as onions, ginkgo biloba, and tea ...

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“…Circulating metabolites of flavonoids, such as glucuronides, sulphates and conjugated O-methylated forms, or intracellular metabolites like flavonoid-GSH adducts, have significantly reduced antioxidant potential relative to the forms found in plants [102]. Indeed, studies have indicated that although such conjugates and metabolites may participate antioxidant reactions and may scavenge reactive oxygen and nitrogen species in the circulation, their effectiveness to do so is reduced compared to their parent aglycones [22,70,94,117,132].…”

Section: Absorption Metabolism and Distribution Of Flavonoidsmentioning

confidence: 99%

The neuroprotective potential of flavonoids: a multiplicity of effects

et al. 2008

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Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

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Protection by quercetin and quercetin 3-O-β-D-glucuronide of peroxynitrite-induced antioxidant consumption in human plasma low-density lipoprotein

Cited by 62 publications

References 34 publications

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

Absorption of kaempferol from endive, a source of kaempferol-3-glucuronide, in humans

Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages

The neuroprotective potential of flavonoids: a multiplicity of effects

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