Desirée Camuesco

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

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 glycosides 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‐κB 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‐κB pathway.

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

Quercitrin, 3‐rhamnosylquercetin, is a bioflavonoid with antioxidant properties, which exerts anti‐inflammatory activity in experimental colitis. In the present study, different in vivo experiments were performed in order to evaluate the mechanisms of action involved in this effect, with special attention to its effects on proinflammatory mediators, including nitric oxide (NO). Experimental colitis was induced in female Wistar rats by incorporation of dextran sodium sulfate (DSS) in drinking water. Oral treatment of quercitrin (1 or 5 mg kg−1 day−1) to colitic rats ameliorated the evolution of the inflammatory process induced when administered in a preventative dosing protocol. When quercitrin (1 mg kg−1 day−1) was administered on established colitis, it facilitated the recovery of the inflamed mucosa. The beneficial effects exerted by quercitrin were evidenced both histologically and biochemically, and were associated with an improvement in the colonic oxidative status, altered as a consequence of the colonic insult induced by DSS. In addition, a reduction of colonic NO synthase activity was observed, probably related to a decreased expression in the inducible form of the enzyme via downregulation in the colonic activity of the nuclear factor‐κB. Immunohistochemical studies showed that quercitrin treatment reduced macrophage and granulocyte infiltration in the inflamed tissue.

A comparative study of the preventative effects exerted by three probiotics, Bifidobacterium lactis, Lactobacillus casei and Lactobacillus acidophilus, in the TNBS model of rat colitis.

Aims:  The intestinal anti‐inflammatory effects of three probiotics with immunomodulatory properties, Lactobacillus casei, Lactobacillus acidophilus and Bifidobacterium lactis, were evaluated and compared in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis.

Preventative effects of lactulose in the trinitrobenzenesulphonic acid model of rat colitis.

Aims: Lactulose is a drug used as a laxative that has been shown to promote the growth of lactobacilli and bifidobacteria, acting as a prebiotic and with a potential beneficial effect in inflammatory bowel disease. The present study describes the preventive antiinflammatory activity of lactulose in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis. Methods: Rats were rendered colitic by a colonic instillation of 10 mg of TNBS dissolved in 0.25 mL of 50% ethanol. One group of colitic rats received lactulose, which was incorporated in the drinking water (2.5% wt/vol) for 2 weeks before TNBS instillation, and colonic damage was evaluated 1 week after colitis induction. Different biochemical markers of colonic inflammation were assayed: myeloperoxidase activity, glutathione content, tumor necrosis factor &agr;, leukotriene B4 levels, and colonic inducible nitric oxide synthase expression. In addition, bacterial counts (for lactobacilli and bifidobacteria) were performed in colonic contents from colitic rats. Results: The results show that lactulose exerted a preventive antiinflammatory effect in this model of rat colitis, as evidenced by a significant reduction of myeloperoxidase activity and by a decrease of both colonic tumor necrosis factor &agr; and leukotriene B4 production. This effect was also characterized by an inhibition of colonic inducible nitric oxide synthase expression, which is unregulated as a consequence of the inflammatory status. This beneficial effect was associated with increased levels of lactobacilli and bifidobacteria species in colonic contents in comparison with untreated colitic rats. Conclusion: In conclusion, the intestinal antiinflammatory effect of lactulose could be related to its prebiotic properties, supporting its potential use in human inflammatory bowel disease.

The combination of fructooligosaccharides and resistant starch shows prebiotic additive effects in rats

Different types of dietary fiber can be distinguished considering their rate of fermentability, thus determining the location of the large intestine where they exert their beneficial effect. Their combination could be interesting to obtain health-promoting effects throughout the entire colon. The aim of the present study was to evaluate the synergistic effect of two dietary fibers with different fermentation patterns, fructooligosaccharides (FOS) (Beneo(®)-95) and resistant starch (Fibersol(®)-2), after their administration to healthy rats or in trinitrobenzenesulphonic acid-(TNBS) colitic rats, with an altered colonic immune response. In healthy rats, the administration of the combination of FOS and resistant starch induced changes in the intestinal microbiota, by increasing lactobacilli and bifidobacteria in caecum and colonic contents. Furthermore, its administration up-regulated the expression of the trefoil factor-3 and MUC-2 in comparison with untreated rats, thus improving the intestinal barrier function. The beneficial effects observed with this combination were confirmed in the TBNS model of rat colitis, since it was able to exert intestinal anti-inflammatory effect, associated with an increase of protective bacteria and up-regulation of epithelial defense mechanisms. In conclusion, the combination of two different dietary fibers may result in a synergistic prebiotic effect, and may confer greater health benefits to the host.

Intestinal anti-inflammatory activity of dietary fiber (Plantago ovata seeds) in HLA-B27 transgenic rats

BACKGROUND & AIMS Dietary fiber has been proven to be beneficial in maintaining remission in human ulcerative colitis, an effect related with an increased luminal production of short-chain fatty acids (SCFA). The aim of the present study was to further investigate the mechanisms involved in the intestinal anti-inflammatory effects of dietary fiber in an experimental model of rat colitis. METHODS HLA-B27 transgenic rats (8-10 weeks old) were fed a fiber-supplemented diet (5% Plantago ovata seeds) for 13 weeks before evaluation of the colonic inflammatory status, both histologically and biochemically. The luminal colonic production of SCFA was quantified. In vitro studies were also performed to test the interaction between two SCFA (butyrate and propionate) as inhibitors of cytokine production in THP-1 cells. RESULTS Dietary fiber supplementation ameliorated the development of colonic inflammation in transgenic rats as evidenced by an improvement of intestinal cytoarchitecture. This effect was associated with a decrease in some of the pro-inflammatory mediators involved in the inflammatory process: nitric oxide, leukotriene B(4), tumor necrosis factor alpha (TNFalpha). The intestinal contents from fiber-treated colitic rats showed a significant higher production of SCFA, butyrate and propionate, than non-treated colitic animals. In vitro studies revealed a synergistic inhibitory effect of butyrate and propionate on TNFalpha production. CONCLUSIONS Dietary fiber supplementation ameliorated colonic damage in HLA-B27 transgenic rats. This effects was associated with an increased production of SCFA, which can act synergistically in inhibiting the production of pro-inflammatory mediators.

A probiotic strain of Escherichia coli, Nissle 1917, given orally exerts local and systemic anti-inflammatory effects in lipopolysaccharide-induced sepsis in mice

Background and purpose:  Escherichia coli Nissle 1917 is a probiotic strain used in the treatment of intestinal immune diseases, including ulcerative colitis. The aim of the present study was to test if this probiotic bacterium can also show systemic immunomodulatory properties after oral administration.

Evaluation of the preventative effects exerted by Lactobacillus fermentum in an experimental model of septic shock induced in mice

The preventative effects of the probiotic Lactobacillus fermentum CECT5716 were evaluated in the lipopolysaccharide (LPS) model of septic shock in mice. The probiotic was administered suspended in drinking water at the final concentration of 108 colony-forming units/ml for 2 weeks before the induction of an endotoxic shock by an intraperitoneal injection of LPS (400 microg/200 microl per mouse). Blood and different organs were collected after 24 h to evaluate the severity of the endotoxic shock and the preventative effects of the probiotic. L. fermentum reduced TNF-alpha levels in blood, which promotes the major alterations observed during septic shock, as well as the infiltration of activated neutrophils into the lungs. Furthermore, free radical overproduction and oxidative stress were associated with a significant decrease in hepatic glutathione levels in septic mice, and with an excessive NO production attributed to the induction of the inducible isoform of NO synthase (iNOS). In fact, hepatic glutathione levels were significantly increased in the group of mice receiving the probiotic, and the increased iNOS expression both in the colon and lungs was down-regulated in those mice treated with L. fermentum. Finally, pre-treatment with L. fermentum may also exert its protective action modulating the expression of different cytokines in splenocyte-derived T cells such us IL-2, IL-5, IL-6 or IL-10. In conclusion, pre-treatment with L. fermentum may exert its protective action against LPS-induced organ damage in mice by a combination of several actions including its antioxidant properties and by reduction of the synthesis of the pro-inflammatory TNF-alpha and IL-6.

The intestinal anti-inflammatory effect of minocycline in experimental colitis involves both its immunomodulatory and antimicrobial properties

Some antibiotics, including minocycline, have recently been reported to display immunomodulatory properties in addition to their antimicrobial activity. The use of a compound with both immunomodulatory and antibacterial properties could be very interesting in the treatment of inflammatory bowel disease (IBD), so the aim of our study was to evaluate the anti-inflammatory effect of minocycline in several experimental models of IBD. Firstly, the immunomodulatory activity of the antibiotic was tested in vitro using Caco-2 intestinal epithelial cells and RAW 264.7 macrophages; minocycline was able to inhibit IL-8 and nitrite production, respectively. In vivo studies were performed in trinitrobenzenesulfonic acid (TNBS)-induced rat colitis and dextran sodium sulfate (DSS)-induced mouse colitis. The results revealed that minocycline exerted an intestinal anti-inflammatory effect when administered as a curative treatment in the TNBS model, modulating both immune and microbiological parameters, being confirmed in the DSS model; whereas none of the other antibiotics tested (tetracycline and metronidazole) showed anti-inflammatory effect. However, minocycline administration before the colitis induction was not able to prevent the development of the intestinal inflammation, thus showing that only its antimicrobial activity is not enough for the anti-inflammatory effect. In conclusion, minocycline displays an anti-inflammatory effect on different models of rodent colitis which could be attributed to the association of its antibacterial and immunomodulatory properties.

The intestinal anti-inflammatory effect of dersalazine sodium is related to a down-regulation in IL-17 production in experimental models of rodent colitis.

BACKGROUND AND PURPOSE Dersalazine sodium (DS) is a new chemical entity formed by combining, through an azo bond, a potent platelet activating factor (PAF) antagonist (UR‐12715) with 5‐aminosalicylic acid (5‐ASA). DS has been demonstrated to have anti‐inflammatory effects on trinitrobenzene sulphonic acid (TNBS)‐induced colitis in rats and recently in UC patients in phase II PoC. There is Increasing evidence that Th17 cells have an important role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to further characterize the anti‐inflammatory effects of DS.