Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure–activity relationships

Kim, Hee Kee; Cheon, Bong Sun; Kim, Young Ha; Kim, Sung Yong; Kim, Hyun Pyo

doi:10.1016/s0006-2952(99)00160-4

Cited by 508 publications

(294 citation statements)

References 19 publications

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“…We decided to evaluate their in vitro effects in inhibiting macrophage functions, immune cells that are extensively involved in the initiation and progression of the inflammation process observed in IBD [13,14]. Our results showed that quercetin, but not quercitrin, was able to inhibit both macrophage proliferation and activation, measured as [ 3 H]thymidine incorporation induced by M-CSF or iNOS and cytokine expression induced by LPS, in accordance with previous results reported by others [31]. These results would suggest that the use of the aglycone quercetin should be the best choice for the treatment of IBD.…”

Section: Discussionsupporting

confidence: 84%

In vivo quercitrin anti‐inflammatory effect involves release of quercetin, which inhibits inflammation through down‐regulation of the NF‐κB pathway

et al. 2005

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Quercetin is a common antioxidant flavonoid found in vegetables, which is usually present in glycosylated forms, such as quercitrin (3-rhamnosylquercetin). Previous in vitro experiments have shown that quercetin exerts a bigger effect than quercitrin in the down-regulation of the inflammatory response. However, such results have not been reproduced in in vivo experimental models of intestinal inflammation, in which quercetin did not show beneficial effects while its glycosides, quercitrin or rutin, have demonstrated their effectiveness. In this study, we have reported that the in vivo effects of quercitrin in the experimental model of rat colitis induced by dextran sulfate sodium can be mediated by the release of quercetin generated after glycoside's cleavage by the intestinal microbiota. This is supported by the fact that quercetin, but not quercitrin, is able to down-regulate the inflammatory response of bone marrow-derived macrophages in vitro. Moreover, we have demonstrated that quercetin inhibits cytokine and inducible nitric oxide synthase expression through inhibition of the NF-jB pathway without modification of c-Jun N-terminal kinase activity (both in vitro and in vivo). As a conclusion, our report suggests that quercitrin releases quercetin in order to perform its anti-inflammatory effect which is mediated through the inhibition of the NF-jB pathway.

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Section: Discussionsupporting

confidence: 84%

In vivo quercitrin anti‐inflammatory effect involves release of quercetin, which inhibits inflammation through down‐regulation of the NF‐κB pathway

et al. 2005

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“…Flavonoids act at other cellular levels, for example, inhibition of iNOS enzyme activity (Kobuchi et al, 1999), iNOS protein expression (Kim et al, 1999;Liang et al, 1999;van Meeteren et al, 2004) and transcription of nuclear factor kB (NFkB) (Choi et al, 2003). Interactions between flavonoids and the antioxidant network have been described.…”

Section: Thiol-based Antioxidantsmentioning

confidence: 99%

Antioxidants and polyunsaturated fatty acids in multiple sclerosis

Meeteren¹,

Teunissen

Dijkstra

et al. 2005

Eur J Clin Nutr

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“…In this regard, it is very interesting that several studies have shown that specific flavonoids can suppress the induction of iNOS gene and protein expression, and NO • production by cytokines and endotoxins in mouse macrophage RAW 264.7 cells [99,109,152]. The mechanism did not include a direct inhibitory effect on enzyme activity, but rather the modulation of cell signaling pathways necessary for NOS gene expression.…”

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

“…Recent reports demonstrated that the induction of iNOS expression following treatment with LPS or interferon-␥ [108], as well as the expression of nNOS requires the ERK1/2 signaling pathway, providing a potentially interesting link between MAPK signaling, nitric oxide production, and mitochondrial function. Since epicatechin and kaempferol have been shown to attenuate the oxidative stress-mediated activation of ERK1/2 [178] it remains to be established whether or not these flavonoids are capable of suppressing the production of NO • in neurons and glial cells in vivo as reported for iNOS in cultured macrophages [99,109,154], and what influences this may have on cellular outcomes of oxidative insults.…”

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

310

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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Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structure–activity relationships

Cited by 508 publications

References 19 publications

In vivo quercitrin anti‐inflammatory effect involves release of quercetin, which inhibits inflammation through down‐regulation of the NF‐κB pathway

In vivo quercitrin anti‐inflammatory effect involves release of quercetin, which inhibits inflammation through down‐regulation of the NF‐κB pathway

Antioxidants and polyunsaturated fatty acids in multiple sclerosis

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

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