Food supplementation with rice bran enzymatic extract prevents vascular apoptosis and atherogenesis in ApoE-/- mice.

PURPOSE: Atherosclerosis is associated with reduced mononuclear cell (MNC) telomere length, and senescent cells have been detected in atherosclerotic plaques. Rice bran is a source of γ-oryzanol, phytosterols and tocols with potential lipid-lowering, antioxidant and anti-inflammatory activities. Here, we tested the hypothesis that rice bran enzymatic extract (RBEE) impacts on apoptosis, telomere length and atherogenesis in mice. METHODS: Seven-week-old male ApoE-/- mice were fed high-fat diet (HFD) or isocaloric HFD supplemented with 5 % (w/w) RBEE for 23 weeks. Wild-type mice of the same age were kept under standard diet as controls. RESULTS: RBEE treatment reduced total cholesterol (19.24 ± 1.63 vs 24.49 ± 1.71 mmol/L) and triglycerides (1.13 ± 0.18 vs 1.75 ± 0.22 mmol/L) and augmented HDL-cholesterol (1.86 ± 0.20 vs 1.07 ± 0.20 mmol/L). RBEE attenuated macrophage infiltration by 56.69 ± 4.65 % and plaque development (7737 ± 836 vs 12,040 ± 1001 µm2) in the aortic sinus. In the aorta, RBEE treatment reduced expression of the apoptosis pathway components p16, p53 and bax/bcl-2 ratio. RBEE prevented apoptosis of aortic endothelial cells (2.81 ± 0.71-1.14 ± 0.35 apoptotic nuclei/ring for ApoE-/- HFD and ApoE-/- HFD 5 % RBEE, respectively). In contrast, MNC of RBEE-fed mice exhibited enhanced apoptosis marker expression with increased p53 and bax/bcl-2 protein levels. Compared to WT, ApoE-/- mice on HFD were characterized by significant telomere shortening in aorta (11 ± 2 %) and MNC (73 ± 7 %), which was reduced by supplementation with RBEE (aorta: 40 ± 7 %; MNC: 105 ± 10 %). Expression of telomere repeat-binding factor 2 was increased in RBEE-fed mice. CONCLUSION: Long-term food supplementation with RBEE lowers cholesterol and prevents atherosclerotic plaque development in ApoE-/- mice. Differential regulation of vascular and MNC apoptosis and senescence were identified as potential mechanisms.

Microvascular disorders in obese Zucker rats are restored by a rice bran diet.

BACKGROUND AND AIM: Nutritional-based approaches aimed to prevent microvascular dysfunction associated to obesity present potential advantages over pharmacological strategies. Our aim was to test whether a rice bran enzymatic extract (RBEE)-supplemented diet could attenuate microvascular alterations in obese rats. METHODS AND RESULTS: Lean and obese Zucker rats were fed standard diet supplemented or not with 1% and 5% RBEE for 20 weeks. Functional studies were performed in small mesenteric arteries in isometric myograph. Immunoblotting and fluorescence studies were made in arterial homogenates and arterial sections, respectively. RBEE-supplementation restored microvascular function in obese rats through a marked increase in NO and endothelial-derived hyperpolarizing factor contribution by up-regulation of eNOS and calcium-activated potassium channels expression, respectively, in association to a substantial reduction of microvascular inflammation and superoxide anion formation. These data agrees with the beneficial actions of RBEE on dyslipidemia, hyperinsulinemia and hypertension in obesity. CONCLUSION: The multi-factorial properties of RBEE-diet, especially for restoring the function of small resistance arteries shows this dietary-based approach to be a promising candidate for prevention of microvascular alterations in obesity, which are crucial in cardiovascular events in obese subjects.

Oleanolic acid induces relaxation and calcium-independent release of endothelium-derived nitric oxide.

BACKGROUND AND PURPOSE: The present study investigated the mechanisms by which oleanolic acid, a component of olive oil, increases release of nitric oxide (NO). EXPERIMENTAL APPROACH: Measurements of isometric tension, NO concentration, or endothelial cell calcium were made in rat isolated mesenteric arteries. Immunoblotting for endothelial NOS (eNOS) and Akt kinase were performed in primary cultures of human umbilical vein endothelial cells (HUVECs). KEY RESULTS: Oleanolic acid (3-30 microM) evoked endothelium-dependent relaxations in noradrenaline-contracted rat superior and small mesenteric arteries. In rat superior mesenteric arteries, oleanolic acid induced simultaneous increases in NO concentration and relaxation, and these responses were inhibited by an inhibitor of NOS, asymmetric dimethyl-L-arginine (300 microM) and by the NO scavenger, oxyhaemoglobin (10 microM). Oleanolic acid-evoked NO increases were not reduced in Ca(2+)-free solution and in the presence of an inhibitor of endoplasmic reticulum calcium-ATPase, thapsigargin (1 microM). Oleanolic acid evoked relaxation without changes in endothelial cell calcium, but decreased smooth muscle calcium in arterial segments. Oleanolic acid failed to increase calcium in HUVECs, but increased time-dependently phosphorylation of Akt kinase at Serine(473) (Akt-Ser(473)) and eNOS at Serine(1177) (eNOS-Ser(1177)), which was attenuated by inhibitors of phosphoinositide-3-kinase. CONCLUSIONS AND IMPLICATIONS: This study provides direct evidence that a component of olive oil, oleanolic acid, activated endothelium-dependent release of NO and decreased smooth muscle cell calcium followed by relaxation. The oleanolic acid-evoked endothelium-derived NO release was independent of endothelial cell calcium and involved phosphoinositide-3-kinase-dependent phosphorylation of Akt-Ser(473) followed by phosphorylation of eNOS-Ser(1177).

[Cognitive effects of combined memory and psychomotor training in elderly adults]. / Efectos cognitivos de un entrenamiento combinado de memoria y psicomotricidad en adultos mayores.

INTRODUCTION: As part of the normal ageing process, cognitive deterioration clearly takes place in memory, attention and the information processing speed (IPS). Among the intervention strategies commonly used, combined programmes like those involving memory and psychomotor skills have the greatest beneficial effects on cognition in the short and long term. AIM: To evaluate the effects of a combined memory and psychomotor training programme entitled 'Independence in Older age' (SIMA) on the cognitive performance of a population sample of healthy elderly adults. SUBJECTS AND METHODS: A cross-sectional study was conducted on 95 elderly adults (49 in the intervention group and 46 in the control group) before and after a 20-session training programme. Both intergroup (intervention group versus control group) and intragroup (each group individually) cognitive performance was analysed. The two groups were paired by age, sex and schooling. RESULTS: The intergroup analysis following the training showed statistically and clinically significant differences in two IPS variables: conflict and interference in the colour-word test, which had a size effect of -1.31 and -1.38, respectively; the performance of the group of trained elderly adults was better than that of the controls. Likewise, in the intragroup analysis significant differences were found in these two variables in the group that received the intervention, with a size effect of -1.27 and -1.15. CONCLUSION: Findings show positive effects of combined SIMA memory and psychomotor training, especially in selective attention and the IPS with a healthy elderly adult population.

Effects of dietary oleic-rich oils (virgin olive and high-oleic-acid sunflower) on vascular reactivity in Wistar-Kyoto and spontaneously hypertensive rats.

The effects of two monounsaturated fatty acid (MUFA)-rich diets, containing virgin olive oil (OO) and high-oleic-acid sunflower oil (HOSO), on development of vascular response from isolated thoracic rat aorta and lipid composition and fatty acid composition were studied and compared with samples from rats fed on a control diet. Dietary MUFA oils were fed for 6 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats from 4 weeks of age. The maximum contraction of aortic ring preparations in response to phenylephrine (10(-6) m) was significantly decreased in SHR rats fed with OO (0.81 (sem 0.05) v. 1.18 (sem 0.09) g, and treatment with HOSO did not alter the phenylephrine-induced contractions. The relaxant responses to acetylcholine (10(-5) m) were significantly enhanced (30.03 (sem 0.70) v. 18.47 (sem 0.28) %, in the rings from SHR rats treated with OO, and were more pronounced than in WKY rats In the same way, OO attenuated the dose-response curves induced by phenylephrine (10(-8)-10(-5) m) from SHR rats, accompanied with a slower contraction. These results suggest that only the chronic feeding of OO diet was able to attenuate the vascular response of rat aorta. In addition, an increase in phospholipid content (186.7 (sd 3.2) v. 159.1 (sd 11.3) g/kg, and changes in the fatty acid composition of aorta (mainly a decrease in arachidonic acid) could contribute to improving endothelial function. Therefore, the effects can not be attributed exclusively to the content of MUFA (mainly oleic acid). Other components of OO, such as polyphenols, not present in HOSO, may help to explain the vascular protective effect of OO consumption.

A pharmacological study of Cecropia obtusifolia Bertol aqueous extract.

Cecropia obtusifolia (Cecropiaceae) is a species from tropical America and its leaves are used in traditional medicine for the treatment of diabetes and as an anti-inflammatory agent. In the present study, the analgesic, anti-inflammatory and central nervous system depressant effects of the aqueous extract from the leaves of C. obtusifolia were investigated in different experimental models, with the purpose of validating its ethnomedical uses. The results obtained with the extract from the leaves of C. obtusifolia reflect a low toxicity, a substantial central depressor effect and analgesic activity and significant motor incoordination and muscle relaxant activity. Concerning the analgesic activity, using the hot plate test, the extract did not produce any effect, however it showed a significant effect on the pain induced by chemical stimuli (acetic and formalin test); this suggests the peripheral analgesic effect of the extract. The extract also showed a topical and systemic anti-inflammatory effect. Thus this work could justify the popular use of C. obtusifolia in rheumatic and kidney inflammation pathologies and reveals that this plant is an interesting species.

In vitro scavenger and antioxidant properties of hesperidin and neohesperidin dihydrochalcone.

We have assesed the actions as free radical scavengers and inhibitors on peroxidation of hesperidin and neohesperidin dihydrochalcone, two flavonoids, flavanone and dihydrochalcone respectively, as some of the pharmacological properties of flavonoids group have been related with these activities. Hesperidin just at 10(-4) and 5 · 10(-4)M is able to show a low inhibitory activity in the superoxide anion radicals (O(2)(-)) genesis (8.66 ± 1.40 and 11.69 ± 2.36% respectively), and on the non-enzymatic lipid peroxidation at 10(-3)M dose (9.78 ± 0.35%), without affecting the hydroxyl radical (•OH) formation, generated by the ascorbic acid-Fe(3+)-EDTA system. In the other hand, neohesperidin dihydrochalcone is an authentic antioxidant drug as tested at all doses. It showed a great scavenger activity and/or inhibition of formation on O(2)(-) radicals (31.53 - 84.62%) and a significant scavenging effect on OH radicals (6.00 - 23.49%), as well as an important inhibitory action on non-enzymatic lipid peroxidation (15.43-95.33%).

Effects of genistein, an isoflavone isolated from Genista tridentata, on isolated guinea-pig ileum and guinea-pig ileal myenteric plexus.

The inhibitory action of the major constituent of Genista tridentata L. (Papilionaceae), 4',5,7-trihydroxyisoflavone (genistein), on contractions induced by agonists and electrical field stimulation of smooth muscle was analysed. Genistein inhibited twitches evoked by electrical-stimulation of strips of guinea-pig ileum with an IC50 value of 34 microM. Genistein (34 microM) inhibited contractions of the guinea-pig ileum by several agonists in a non-selective, antispasmodic action and had no effect on inhibition of 3H-ACh release from ileal myenteric plexus. Genistein (34 microM) produces an increase in cAMP levels of guinea-pig ileum which resulted in a smooth muscle relaxation which leads us to think that there must be a blockade of its phosphodiesterase.

[The pharmacodynamics of Pycnocomon rutifolium (Vahl.) Hoffmans and Link. Anti-inflammatory and antibacterial activity]. / Contribution à l'étude pharmacodynamique de Pycnocomon rutifolium (Vahl.) Hoffmans et Link. Activité antiinflammatoire et antibactérienne.

The acute and subchronic antiinflammatory activity of Pycnocomon rutifolium (Vahl.) Hoffmans and Link has been studied resulting that it is active to acute inflammation. Likewise the antibacterial activity in vivo to a infection by Staphylococcus aureus has been proved outcoming positive.

[Contribution to the pharmacodynamic study of Pycnocomon rutifolium (Vahl.) Hoffmanns. and Link. Analgesic activity and antipyretic activity]. / Contribution à l'étude pharmacodynamique de Pycnocomon rutifolium (Vahl.) Hoffmanns. et Link. Activité analgésique et activité antipyrétique.

We have tested the analgesic and antipyretic activity of the aqueous extract obtained from Pycnocomon rutifolium for various stimulations. Previously we have made a phytochemic screening and an assay of acute toxicity.