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Although butyrate could exert antiproliferative effects in tumor progression, its production is safe and without consequences for the normal epithelium growth.

The intestinal anti-inflammatory effects of two probiotics isolated from breast milk, Lactobacillus reuteri and L. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50 % ethanol (0·25 ml). Either L. reuteri or L. fermentum was daily administered orally (5 £ 10 8 colony-forming units suspended in 0·5 ml skimmed milk) to each group of rats (n 10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated histologically and biochemically, and the colonic luminal contents were used for bacterial studies and for SCFA production. Both probiotics showed intestinal anti-inflammatory effects in this model of experimental colitis, as evidenced histologically and by a significant reduction of colonic myeloperoxidase activity (P,0·05). L. fermentum significantly counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, both probiotics lowered colonic TNFa levels (P,0·01) and inducible NO synthase expression when compared with non-treated rats; however, the decrease in colonic cyclo-oxygenase-2 expression was only achieved with L. fermentum administration. Finally, the two probiotics induced the growth of Lactobacilli species in comparison with control colitic rats, but the production of SCFA in colonic contents was only increased when L. fermentum was given. In conclusion, L. fermentum can exert beneficial immunomodulatory properties in inflammatory bowel disease, being more effective than L. reuteri, a probiotic with reputed efficacy in promoting beneficial effects on human health.

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. Methods and Results:  Colitis was induced in rats by intracolonic administration of 10 mg of TNBS dissolved in 0·25 ml of 50% ethanol. Each probiotic was administered orally (5 × 108 CFU suspended in 0·5 ml of skimmed milk) for 3 weeks, starting 2 weeks before the administration of TNBS. Colonic damage was evaluated histologically and biochemically 1 week after TNBS instillation. The results obtained revealed that all probiotics assayed showed intestinal anti‐inflammatory effects, macroscopically evidenced by a significant reduction in the colonic weight/length ratio. Only B. lactis showed a lower incidence of diarrhoea in comparison with untreated rats. Biochemically, all probiotics restored colonic glutathione levels, depleted as a consequence of the oxidative stress of the inflammatory process. Bifidobacterium lactis treatment reduced colonic tumour necrosis factor (TNF)‐α production, and inducible nitric oxide synthase (iNOS) and cyclo‐oxygenase‐2 (COX‐2) expression; L. acidophilus administration reduced colonic leukotriene B4 production and iNOS expression and L. casei intake was associated with a decrease in colonic COX‐2 expression. Conclusion:  The three probiotics assayed have shown intestinal anti‐inflammatory activity in the TNBS model of rat colitis, although each probiotic shows its own anti‐inflammatory profile. Significance and Impact of the Study:  These probiotics could be considered as potential adjuvants in the treatment of inflammatory bowel disease, although more studies are required in order to demonstrate their efficacy in humans.

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Abstract-Activation of nuclear hormone receptor peroxisome proliferator-activated receptor ␤/␦ (PPAR␤) has been shown to improve insulin resistance and plasma high-density lipoprotein levels, but nothing is known about its effects in genetic hypertension. We studied whether the PPAR␤ agonist GW0742 might exert antihypertensive effects in spontaneously hypertensive rats (SHRs). The rats were divided into 4 groups, Wistar Kyoto rat-control, Wistar Kyoto rat-treated (GW0742, 5 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 by oral gavage), SHR-control, and SHR-treated, and followed for 5 weeks. GW0742 induced a progressive reduction in systolic arterial blood pressure and heart rate in SHRs and reduced the mesenteric arterial remodeling, the increased aortic vasoconstriction to angiotensin II, and the endothelial dysfunction characteristic of SHRs. These effects were accompanied by a significant increase in endothelial NO synthase activity attributed to upregulated endothelial NO synthase and downregulated caveolin 1 protein expression. Moreover, GW0742 inhibited vascular superoxide production, downregulated p22 phox and p47 phox proteins, decreased both basal and angiotensin II-stimulated NADPH oxidase activity, inhibited extracellular-regulated kinase 1/2 activation, and reduced the expression of the proinflammatory and proatherogenic genes, interleukin 1␤, interleukin 6, or intercellular adhesion molecule 1. None of these effects were observed in Wistar Kyoto rats. PPAR␤ activation, both in vitro and in vivo, increased the expression of the regulators of G protein-coupled signaling proteins RGS4 and RGS5, which negatively modulated the vascular actions of angiotensin II. PPAR␤ activation exerted antihypertensive effects, restored the vascular structure and function, and reduced the oxidative, proinflammatory, and proatherogenic status of SHRs. We propose PPAR␤ as a new therapeutic target in hypertension. T he peroxisome proliferator-activated receptors (PPARs) PPAR␣, PPAR␤/␦, and PPAR␥ are members of the nuclear hormone receptor superfamily. PPARs were initially believed to regulate genes involved only in lipid and glucose metabolism. 1 However, in recent years, evidence suggests that activation of PPAR␣ or PPAR␥ may exert cardiovascular protection beyond their metabolic effects. 2 In fact, PPAR␣ or PPAR␥ agonists exert antihypertensive effects in both human and animal models with or without metabolic disorders. [3][4][5][6] The mechanisms underlying the beneficial effects of PPARs beyond glucose and lipid metabolism may relate to their anti-inflammatory and antioxidant actions. 5 Thus, activation of both PPAR␣ or PPAR␥ antagonizes angiotensin II (Ang II) actions, including the activation of NADPH oxidase and the generation of reactive oxygen species, as well as the increase in proinflammatory mediators and adhesion molecules in blood vessels. 5,6 Activation of PPAR␤/␦ (PPAR␤) also exhibits antiinflammatory properties in the vessel wall by inhibiting the expression of vascular cell adhesion molecule 1 and monocyte chemoattractant prote...

The present study analysed the effects of the flavanol (2)-epicatechin in rats after chronic inhibition of NO synthesis with N G -nitro-L-arginine methyl ester (L-NAME), at doses equivalent to those achieved in the studies involving human subjects. Wistar rats were randomly divided into four groups: (1) control-vehicle, (2) L-NAME, (3) L-NAME-epicatechin 2 (L-NAME-Epi 2) and (4) L-NAME-epicatechin 10 (L-NAME-Epi 10). Rats were daily given by oral administration for 4 weeks: vehicle, (2)-epicatechin 2 or 10 mg/kg. Animals in the L-NAME groups daily received L-NAME 75 mg/100 ml in drinking-water. The evolution in systolic blood pressure and heart rate, and morphological and plasma variables, proteinuria, vascular superoxide, reactivity and protein expression at the end of the experiment were analysed. Chronic (2 )-epicatechin treatment did not modify the development of hypertension and only weakly affected the endothelial dysfunction induced by L-NAME but prevented the cardiac hypertrophy, the renal parenchyma and vascular lesions and proteinuria, and blunted the prostanoid-mediated enhanced endothelium-dependent vasoconstrictor responses and the cyclo-oxygenase-2 and endothelial NO synthase (eNOS) up-regulation. Furthermore, (2)-epicatechin also increased Akt and eNOS phosphorylation and prevented the L-NAME-induced increase in systemic (plasma malonyldialdehyde and urinary 8-iso-PGF 2a ) and vascular (dihydroethidium staining, NADPH oxidase activity and p22 phox up-regulation) oxidative stress, proinflammatory status (intercellular adhesion molecule-1, IL-1b and TNFa up-regulation) and extracellular-signal-regulated kinase 1/2 phosphorylation. The present study shows for the first time that chronic oral administration of (2)-epicatechin does not improve hypertension but reduced pro-atherogenic pathways such as oxidative stress and proinflammatory status of the vascular wall induced by blockade of NO production.Key words: (2 )-Epicatechin: N G -nitro-L-arginine methyl ester: Hypertension: Superoxide: Inflammation Flavanols, such as (2)-epicatechin, catechin and their oligomers, represent a major class of flavonoids that are commonly present in most higher plants, and with high content in certain foods, such as grapes, tea and cocoa. Several epidemiological investigations and dietary interventions in human subjects using flavanol-containing foods indicate an inverse relationship between flavanol intake and the risk of CVD (1 -5) . A very wide range of biological actions of a flavanol-rich diet support these potential cardiovascular protective effects including the improvement of vasodilation (6 -8) , blood pressure (9,10) , insulin resistance (11) , the attenuation of platelet reactivity (12) , and the improvement of immune responses and antioxidant defence system (13) . However, little is known about the molecular mechanisms of flavanol-mediated bioactivities in both humans and animals. The reasons for these shortcomings are, at least in part, based on the fact that food matrices contain a multitude of ...