The intestinal anti‐inflammatory effect of quercitrin is associated with an inhibition in iNOS expression

Camuesco, Desirée; Comalada, Mònica; Rodríguez-Cabezas, Maria Elena; Nieto, Ana; Lorente, M.; Concha, Ángel; Zarzuelo, Antonio; Gálvez, Júlio

doi:10.1038/sj.bjp.0705941

Cited by 227 publications

(194 citation statements)

References 46 publications

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“…Meanwhile, previous studies have demonstrated the beneficial effects of two quercetin glycosides, rutin and quercitrin, in experimental models of rat colitis [11,12], which have also been demonstrated in the present study for quercitrin.…”

Section: Discussionsupporting

confidence: 85%

“…Although in vitro experiments clearly showed that quercetin, but not quercitrin, had anti-inflammatory effects, previous studies of our group have shown that quercitrin [12], but not quercetin (unpublished results), is able to ameliorate the inflam- matory process induced in the trinitrobenzene sulfonic acid (TNBS) model of rat colitis. Now, we extended our results obtained with these flavonoids in the experimental model of colitis after addition of DSS to drinking water, with special attention to the action exerted by the flavonoid treatment on colonic pro-inflammatory cytokine secretion, i.e.…”

Section: Resultsmentioning

confidence: 73%

“…It is important to note that when the glycosylated forms of quercetin are assayed, there is usually a loss of activity in these effects in comparison with those obtained with the aglycone, due to the presence of the sugar moiety in the flavonoid structure [10]. On the contrary, both glycosides, quercitrin and rutoside, have shown to exert intestinal anti-inflammatory effects in experimental models of rat colitis [11,12], whereas no clear effects have been demonstrated for the aglycone form (unpublished results). The aim of this study was to clarify this controversy.…”

Section: Introductionmentioning

confidence: 99%

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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: 85%

Section: Resultsmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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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 can inhibit colitis progress by suppressing the expression of inducible nitric oxide synthase in a colitis model (Camuesco et al, 2004). Additionally, quercetin can inhibit COPD deterioration by suppressing reactive oxygen and reactive nitrogen generation (Ganesan et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression

Meng

et al. 2016

Genet. Mol. Res.

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ABSTRACT. This study aimed to explore the protective effect of quercetin on acute lung injury (ALI) in rats with sepsis and the related mechanism. Rats were administered different doses of quercetin intraperitoneally, and blood samples and lung tissue were collected at 24 h after treatment. Arterial blood gases, lung water content, protein content, and cell counts in bronchoalveolar lavage fluid (BALF) were measured. Morphological changes in lung tissue pathology were observed under a light microscope. Serum intercellular adhesion molecule (ICAM)-1 and macrophage inflammatory protein 2 (MIP-2) levels were detected and ICAM-1 and MIP-2 mRNA expression in lung tissue was determined. Compared with that in the control model group, arterial blood gases, lung water content, protein content, and cell counts in BALF improved in the high-and low-dose quercetin groups (P < 0.05), with maximal improvement observed for the highdose quercetin (P < 0.05). Lesions on the lungs improved in the high- and low-dose quercetin groups than those in the control model group, and the high-dose quercetin group showed better improvement than the low-dose group (P < 0.05). Compared with that in the sham-operated group, both serum and lung tissue ICAM-1 and MIP-2 expression increased significantly in the model group (P < 0.05). The quercetin groups presented lower ICAM-1 and MIP-2 expression than the control model group, with the lowest expression observed in the high-dose group (P < 0.05). Quercetin may protect against ALI in rats with sepsis by inhibiting ICAM-1 and MIP-2 expression.

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“…Indeed, flavonoid treatment counters colitis-induced glutathione depletion. On the other hand, quercitrin treatment reduces macrophage infiltration in the dextran sulfate sodium colitis model (6) . The effects of flavonoids on primary macrophages have been studied and their structure-activity relationship characterized (7) .…”

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confidence: 99%

Polyphenols and immunity

Medina¹,

Zarzuelo²

2008

Proc. Nutr. Soc.

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Flavonoids are biologically-active polyphenolic compounds with antioxidative, antineoplasic, cardiovascular protective and antiinflammatory properties. Pharmacological therapy is essential in inflammatory bowel disease but has many adverse effects and does not cure the disease. Flavonoids are excellent candidates because of their anti-inflammatory properties and their low toxicity. Several flavonoids have been shown to exert intestinal anti-inflammatory activity in vivo, including (mg/kg) quercitrin 1-5 (1) , rutin 10-25 (2) , morin 25 (3,4) , hesperidin and diosmin 10-25 (5) . However, the mechanism of action is unclear. Since inflammation is associated by significant oxidative stress, this mechanism may be relevant. Indeed, flavonoid treatment counters colitis-induced glutathione depletion. On the other hand, quercitrin treatment reduces macrophage infiltration in the dextran sulfate sodium colitis model (6) . The effects of flavonoids on primary macrophages have been studied and their structure-activity relationship characterized (7) . A number of flavonoids inhibit macrophage proliferation (but not cell viability) and some additionally reduce TNF and inducible NO synthase (iNOS) expression, probably interfering with the NF-kB pathway. The structural determinants of activity include the C-2 --C-3 double bond, the catechol group in the B ring and the 2-position of the B ring.Most of these flavonoids are glycosides, which are known to be hydrolysed by bacterial enzymes in the gut. Since luteolin and quercetin are not active in vivo and aglycone flavonoids are absorbed in the small intestine it is likely that glycosides act as prodrugs, releasing the biologically-active aglycone in the lumen and preventing their premature absorption, which has been proven in the case of quercitrin (8) . In particular, a faecal homogenate was shown to mediate quercetin release from quercitrin in vitro, and the resulting aglycone retained TNF, iNOS and IL-1b inhibitory activity in murine bone marrow-derived macrophages. This principle probably applies to the other heterosides with known intestinal anti-inflammatory activity.In conclusion, flavonoids have intestinal anti-inflammatory activity that is associated with macrophage inhibition and antioxidative effects. Further investigation of the mechanistic aspects of flavonoid pharmacological action is underway.

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The intestinal anti‐inflammatory effect of quercitrin is associated with an inhibition in iNOS expression

Cited by 227 publications

References 46 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

Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression

Polyphenols and immunity

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