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The aim of the present study was to verify whether extra-virgin olive oil, a dietary component naturally containing phenolic antioxidants, has the potential to protect the brain from the deleterious effects of ageing. To accomplish this goal, we used male rats fed a high-energy diet containing either maize oil, or extra-virgin olive oil with high or low phenol content (720 or 10 mg total phenols/kg oil, corresponding to a daily dose of 4 or 0·05 mg total phenols/kg body weight, respectively) from age 12 months to senescence. The measured endpoints were biochemical parameters related to oxidative stress and functional tests to evaluate motor, cognitive and emotional behaviour. Olive oil phenols did not exert major protective actions on motor and cognitive function, as we observed only a tendency to improved motor coordination on the rotarod in the old animals treated with the oil rich in phenols (40 % average increase in the time to first fall; P = 0·18). However, an interesting finding of the present study was a reduced step-through latency in the light–dark box test, found in the older animals upon treatment with the oil rich in antioxidant phenols, possibly indicating an anxiety-lowering effect. This effect was associated with decreased glutathione reductase activity and expression in the brain, a phenomenon previously associated with decreased anxiety in rodents. These results indicate a previously undetected effect of a diet containing an olive oil rich in phenols. Further studies are warranted to verify whether specific food antioxidants might also have an effect on emotional behaviour.
Inflammatory bowel diseases (IBD) are immunomediated ailments affecting millions of individuals. Although diet is regarded as an important factor influencing IBD, there are no accepted dietary recommendations presently available. We administered 7·6 % lyophilised apples obtained from two cultivars (Golden Delicious and Marie Ménard, low and high in polyphenols, respectively) to HLA-B27 transgenic rats which develop spontaneous IBD. After 3 months feeding, rats fed Marie Ménard apples had reduced myeloperoxidase activity (3·6 (sem 0·3) v. 2·2 (sem 0·2) U/g tissue; P < 0·05) and reduced cyclo-oxygenase-2 (P < 0·05) and inducible NO synthase gene expression (P < 0·01) in the colon mucosa and significantly less diarrhoea (P < 0·05), compared with control rats. Cell proliferation in the colon mucosa was reduced significantly by feeding Golden Delicious apples, with a borderline effect of Marie Ménard apples. Gene expression profiling of the colon mucosa, analysed using the Whole Rat Genome 4 × 44 K Agilent Arrays, revealed a down-regulation of the pathways of PG synthesis, mitogen-activated protein kinase (MAPK) signalling and TNFα–NF-κB in Marie Ménard-fed rats. In the stools of the animals of this group we also measured a significant reduction of bacteria of the Bacteriodes fragilis group. In conclusion, the administration of Marie Ménard apples, rich in polyphenols and used at present only in the manufacturing of cider, ameliorates colon inflammation in transgenic rats developing spontaneous intestinal inflammation, suggesting the possible use of these and other apple varieties to control inflammation in IBD patients.
p-Coumaric acid (3-(4-hydroxyphenyl)-2-propenoic acid; 4CA), is a ubiquitous plant metabolite with antioxidant and anti-inflammatory properties. The antiplatelet activity of this compound was analysed both ex vivo and in vitro. 4-CA, administered to rabbits for 2 weeks at the dose of 5 mg/kg, mixed with food, inhibited ADP-induced platelet aggregation without affecting blood coagulation. This effect was associated with a marked increase in plasma antioxidant activity, measured as ferric reducing ability of plasma, and with the reduction of thromboxane B2 production. The antiplatelet effect was confirmed by in vitro experiments on human blood: 4CA (500 μm and 1 mm) reduced ADP-induced platelet aggregation (55·2 (se 4·01) % and 35·6 (se 2·35) % relative to basal level, respectively). 4CA was able to modify platelet function, measured with PFA-100™, a shear-inducing device that simulates primary haemostasis. 4CA interfered also with arachidonic acid cascade, reducing thromboxane B2 production and lipopolysaccharide-induced prostaglandin E2 generation (ic50 371 and 126 μm, respectively). The data show that 4CA is an antioxidant compound with good antiplatelet activity at doses that can be obtained with dietary intervention, suggesting possible applications for primary prevention of vascular disease.
The effect of 4-coumaric and 3,4-dihydroxybenzoic (protocatechuic) acid on the basal oxidative DNA damage of rat colonic mucosa in vivo was studied, relative to vitamin E. F344 rats were treated with 4-coumaric or protocatechuic acid mixed in the diet (25 or 50 mg/kg for 2 weeks). It was observed that 4-coumaric acid (50 mg/kg) significantly decreased the basal level of the oxidative damage assessed as 8-OH-2′-deoxyguanosine levels in DNA and by the comet assay. Moreover, it was found that vitamin E (10 mg/kg) had no effect on colonic mucosa oxidation damage, whereas at a higher dose (55 mg/kg) it actually enhanced oxidative stress. The effect of 4-coumaric acid (50 mg/kg) on the expression of some glutathione-related enzymes (glutathione-S-transferase (GST)-P, GST-M2, GST-M1, γ-glutamylcysteine synthetase, glutathione peroxidase (GSPX)1 and GSPX4) was also investigated at the level of the colonic mucosa. Only the expression of GST-M2 was significantly induced by 4-coumaric acid, while protocatechuic acid was inactive. The data suggest that 4-coumaric acid acts as an antioxidant in the colonic mucosa in vivo.
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