The Short-Term Effect of Olive Oil Extract Enriched with Hydroxytyrosol on Cardiovascular Function.

Olive is rich in polyphenols such as hydroxytyrosol (HT) that have antioxidative and anti-inflammatory effects. In this study, we examined the short-term effects of olive oil extract (OE) enriched with HT on left atrial function, left ventricular (LV) function, and arterial elastic properties in patients with chronic coronary artery disease (CAD). Sixty-one patients with chronic CAD were enrolled. This randomized study had a two-period, two-sequence crossover (AB/BA) design. Group AB (n = 32) initially received OE capsules (500 mg) enriched with HT (5 mg) (two capsules/day) for 30 days, and after a wash out of 48 h, placebo for another 30 days. The opposite occurred in Group BA (n = 29). Exclusion criteria included age >70 years, diabetes, anemia, hypertension, liver and thyroid disease, malignancy, autoimmune disease, kidney disease, use of corticosteroids, weight loss, excessive exercise dietary intervention, and use of antioxidant vitamins. Patients underwent echocardiography/Doppler and applanation tonometry applied to radial artery at the beginning and end of the study. No significant change regarding Vmax, Vp, Vmin, E wave, A wave, deceleration time, LV ejection fraction, central aortic systolic and pulse pressure, and augmentation index. However, a trend toward improvement of E/e' (P = .062) and pulse wave velocity (P = .091) was observed. Use of OE enriched with HT for a limited time period was associated with a trend toward improvement of LV diastolic function and aortic elastic properties in chronic CAD patients. Studies of longer duration are needed to delineate the effect of this promising agent on cardiovascular function and outcomes in chronic CAD.

Novel Evidence-Based Combination of Plant Extracts with Multitarget Mechanisms of Action for the Elimination of Hot Flashes during Menopause.

Hot flashes are considered the most bothersome complaint during menopause. Although hormone therapy is an effective option to relieve hot flashes, it has been associated with significant side effects. The aim of our study is to suggest a novel combination of different plant extracts with distinct mechanisms of action against hot flashes. We selected the rhizome of Glycyrrhiza glabra L. (Fabaceae), the rhizome of Actaea racemosa L. (Ranunculaceae), the aerial parts of Hypericum perforatum L. (Hypericaceae) to produce extracts rich in bioactive phytochemicals and the seed oil of Oenothera biennis L. (Onagraceae). We investigated their estrogenic and antioxidant potential and their inhibitory effect against prostaglandin D2 receptor 1 (DP1) as a novel mechanistic pathway for vasodilation in hot flashes, alone or in combination. The phytochemical footprint of the extracts was analyzed using HPLC-PDA and UPLC-HRMS. We observed that the tested extracts possess different mechanisms of action. A. racemosa exerts a beneficial activation of the estrogen receptor, H. perforatum possesses the highest antioxidant capacity and the seed oil of O. biennis inhibits the DP1 receptor. The triple combination in the optimal doses pertains to efficacy against all three mechanisms of action, serves as a multitarget plant-based therapy and could serve as a novel strategy for the alleviation of hot flashes in postmenopausal women.

"Pistacia lentiscus L." reduces the infarct size in normal fed anesthetized rabbits and possess antiatheromatic and hypolipidemic activity in cholesterol fed rabbits.

HYPOTHESIS/PURPOSE: The aim of the present study was to evaluate in vivo the potential anti-ischemic and antiatheromatic activity of Chios Mastic gum, the resin of the trunk and branches of "Pistacia lentiscus var. chia", used since antiquity in traditional Greek medicine. The main compounds of mastic are triterpenes, possessing phytosterol-like structures. This led to the hypothesis that mastic and particularly its neutral fraction, enriched in phytosterol-like compounds, possess antiatheromatic activities. METHODS: Total Mastic Extract without Polymer (TMEWP) and the neutral mastic fraction (NMF) were administered orally for 6 weeks to normal fed and to cholesterol fed rabbits in the form of sunflower oil solution. All the animals were randomly divided into 6 groups, anesthetized and subjected to 30min ischemia of the heart, followed by 3h reperfusion: At the end of the experiment the area at risk and the infarct zone were determined with the aid of fluorescent particles and triphenyl tetrazolium chloride staining, and small segments of the ascending and descending aorta and the heart were taken for histologic examination. Blood samples were collected at different time points of ischemia and reperfusion, for malondialdehyde (MDA) evaluation as an index of lipid peroxidation, for total and LDL cholesterol determination and for evaluation of oxidized LDL. RESULTS: In the normal fed animals the NMF and the TMEWP reduced significantly the infarct size, while in the hypercholesterolemic rabbits both treatments were ineffective. Atherosclerosis was detected in all the animals fed cholesterol enriched diet in the form of subintimal accumulation of lipids and foamy macrophages. There was no detection of atherosclerosis in Groups treated with TMEWP and NMF, which both reduced the total cholesterol levels by 47 and 88% respectively, whilst had not effect on LDL oxidation. TMEWP and NMF reduced the MDA concentration in normal fed rabbits, but had no effect on MDA levels in cholesterol fed animals. TMEWP and NMPF reduce the infarct size in normal animals and possess significant antiatheromatic and hypolipidemic activities in rabbits fed cholesterol enriched diet.

Effects of the olive tree leaf constituents on myocardial oxidative damage and atherosclerosis.

The olive (Olea europaea) leaf is considered an important traditional herbal medicine utilized against infectious diseases, and for the treatment of diabetes and hypertension. Moreover, olive leaf constituents have been related to cardioprotection, probably due to their association with cellular redox modulating effects. The pathogenesis of certain common diseases, including those of the cardiovascular system, involves oxidative stress and tissue inflammation. Olive polyphenolic compounds, such as oleuropein, hydroxytyrosol, or tyrosol, possess antioxidant, anti-inflammatory, antiatherosclerotic, anti-ischemic, and hypolipidemic effects on the myocardium as demonstrated by various in vitro and in vivo studies. In this review article, we summarize the current knowledge on the role of the olive leaf constituents in the prevention of cardiac dysfunction and highlight future perspectives in their use as cardioprotective agents in therapeutics.

The natural olive constituent oleuropein induces nutritional cardioprotection in normal and cholesterol-fed rabbits: comparison with preconditioning.

Ischemic preconditioning, which is mediated by cell signaling molecules, protects the heart from ischemia-reperfusion injury by limiting the infarct size. Oleuropein, the main polyphenolic constituent of olives, reduced the infarct size in normal and cholesterol-fed rabbits when it was administered at a nutritional dose. The aim of the present study was to compare the effects of oleuropein and preconditioning in terms of the cell signaling and metabolism pathways underlying myocardial protection. Rabbits were randomly divided into six groups: the control group received 5 % dextrose for six weeks, the preconditioning group was subjected to two cycles of preconditioning with 5 min ischemia/10 min reperfusion, the O6 group was treated with oleuropein for six weeks, the Chol group was fed a cholesterol-enriched diet and 5 % dextrose for six weeks, and the CholO6 and CholO3 groups were treated with cholesterol and oleuropein for six and three weeks, respectively; oleuropein was dissolved in 5 % dextrose solution and was administered orally at a dose of 20 mg × kg(-1) × day(-1). All animals were subsequently subjected to 30 min myocardial ischemia followed by 10 min of reperfusion. At that time, myocardial biopsies were taken from the ischemic areas for the assessment of oxidative and nitrosative stress biomarkers (malondialdehyde and nitrotyrosine), and determination of phosphorylation of signaling molecules involved in the mechanism of preconditioning (PI3K, Akt, eNOS, AMPK, STAT3). The tissue extracts NMR metabolic profile was recorded and further analyzed by multivariate statistics. Oxidative biomarkers were significantly reduced in the O6, CholO6, and CholO3 groups compared to the control, preconditioning, and Chol groups. Considering the underlying signaling cascade, the phosphorylation of PI3K, Akt, eNOS, AMPK, and STAT-3 was significantly higher in the preconditioning and all oleuropein-treated groups compared to the control and Chol groups. The NMR-based metabonomic study, performed through the analysis of spectroscopic data, depicted differences in the metabolome of the various groups with significant alterations in purine metabolism. In conclusion, the addition of oleuropein to a normal or hypercholesterolemic diet results in a preconditioning-like intracellular effect, eliminating the deleterious consequences of ischemia and hypercholesterolemia, followed by a decrease of oxidative stress biomarkers. This effect is exerted through inducing preconditioning-involved signaling transduction. Nutritional preconditioning may support the low cardiovascular morbidity and mortality associated with the consumption of olive products.

The effect of the phytoestrogen genistein on myocardial protection, preconditioning and oxidative stress.

INTRODUCTION: We have previously shown that estrogen administered in ovariectomized female rabbits significantly reduce myocardial infarct size. We now investigated whether the phytoestrogen genistein similarly protects ischemic myocardium and whether this is associated with its antioxidant properties. In addition, we examined whether genistein abolishes preconditioning, since at high doses, it inhibits tyrosine kinase. MATERIALS AND METHODS: We studied five groups of New Zealand white female rabbits. Group A (n = 12) were normal controls, group B (n = 14) were ovariectomized 4 weeks prior to the experiment, group C (n = 10) were ovariectomized and treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment, group D (n = 12) had intact gonads and were treated with genistein (0.2 mg kg(-1) day(-1) subcutaneously) for 4 weeks before the experiment and group E (n = 8) were ovariectomized 4 weeks prior to the experiment and treated with a single dose of genistein (0.2 mg kg(-1) day(-1) subcutaneously) just prior to the experiment. All animals underwent 30 min of heart ischemia and 120 min of reperfusion, with (subgroup I) or without (subgroup II) preconditioning. Malondialdehyde (MDA) concentration just before the experiment was determined. RESULTS: We found significant differences between the groups-p < 0.0001 in factorial ANOVA. The groups with preconditioning had significant smaller infarcts compared to those without-AI vs AII (10.66 +/- 1.42% vs 43.22 +/- 2.67%), BI vs BII (18.53 +/- 2.36% vs 43.05 +/- 8.37%), CI vs CII (10.17 +/- 2.07% vs 44.5 +/- 5.47%), DI vs DII (14.98 +/- 2.36% vs 37.79 +/- 3.92%) and EI vs EII (17.11 +/- 3.24% vs 42.08 +/- 3.42%), p < 0.0005. Ovariectomy was not associated with larger myocardial infarctions-AII vs BII, p = NS. Genistein, for 4 weeks, did not protect ischemic myocardium in either ovariectomized or non-ovariectomized animals-BII vs CII and AII vs DII, p = NS. There was no significant difference between the preconditioned animals, with intact gonads or ovariectomized (AI vs BI, p = NS), ovariectomized with or without genistein (BI vs CI, p = NS) and non-ovariectomized whether treated with genistein or not (AI vs DI, p = NS). A single dose of genistein did not offer any protection (EII vs BII, p = NS), nor did it modify the preconditioning effect (EI vs BI, p = NS). We found no significant difference in MDA plasma levels between the groups. CONCLUSION: Genistein, at this dose, does not reduce infarct size per se nor abolishes the protection induced by preconditioning, in both ovariectomized and non-ovariectomized animals. Preconditioning offers myocardial protection in animals with intact gonads as well as estrogen deprived; bilateral ovariectomy, at least during short-term, is not associated with larger myocardial infarcts compared to control animals. In addition estrogen deprivation, during short term, as well as genistein do not modify oxidative stress.

The olive constituent oleuropein exhibits anti-ischemic, antioxidative, and hypolipidemic effects in anesthetized rabbits.

Thgoal of this study was to evaluate the efficacy of the antioxidant olive constituent, oleuropein, on infarct size, oxidative damage, and the metabolic profile in rabbits subjected to ischemia. Oleuropein, 10 or 20 mg/(kg x d), was administered to 8 groups that consumed a normal or hypercholesterolemic diet for 6 wk or only the higher dose for 3 wk. Circulating levels of malondialdehyde, protein carbonyl, nitrite+nitrate, cholesterol, triglycerides, SOD activity, and the metabolic profile were measured using 1H NMR spectra. In rabbits that consumed the normal diet, the infarct size (percentage of infarct to risk areas) was reduced by the administration of 10 mg oleuropein/(kg x d) (16.1 +/- 2.9%) or 20 mg oleuropein/(kg x d) for 3 wk (21.7 +/- 2.2%) or for 6 wk (24.3 +/- 1.3%) compared with the control group (48.05 +/- 2.0%, P < 0.05). Only the higher dose of 20 mg/(kg x d) reduced the infarct size in hypercholesterolemic rabbits (34.7 +/- 4.4% for 6 wk and 34.8 +/- 6.1% for 3 wk) compared with the cholesterol-fed control group (52.8 +/- 2.4%, P < 0.05). Oleuropein decreased the plasma lipid peroxidation product and protein carbonyl concentrations compared with the control groups, in which these factors increased relative to baseline due to ischemia and reperfusion. Furthermore, in rabbits administered oleuropein, RBC superoxide dismutase activity did not change during ischemia and reperfusion. This activity was significantly higher than in both control groups in which it was reduced by ischemia and reperfusion compared with baseline. Treatment for 6 wk with both doses of oleuropein reduced total cholesterol and triglyceride concentrations. 1H NMR spectra revealed a different profile of glycolysis metabolites in the oleuropein-treated groups compared with the controls. Oleuropein, for 3 or 6 wk, reduced the infarct size, conferred strong antioxidant protection and reduced the circulating lipids. This is the first experimental study in vivo that suggests the possibility of using an olive constituent in the treatment of ischemia.

Acute effect of black and green tea on aortic stiffness and wave reflections.

OBJECTIVE: While most studies have shown an inverse relation between tea consumption and cardiovascular risk, other studies have shown opposite results. Aortic stiffness and wave reflections are markers of cardiovascular disease and prognosticators of cardiovascular risk. METHODS: The acute effect of black and green tea on aortic stiffness and wave reflections was assessed in 29 healthy volunteers in a randomized, single-blind, sham-procedure controlled, cross-over design. In the black tea sub-study, 16 subjects received 6 gm of tea, caffeine (175 mg), or hot water in 3 different sessions. In the green tea sub-study, 13 subjects received 6 gm of tea, caffeine (125 mg), or hot water. Carotid-femoral pulse wave velocity and wave reflection indices were measured at baseline and for 3 hours after consumption. RESULTS: Black tea increased pulse wave velocity during the first 90 min (increase by 0.49 m/sec, P < 0.05), showing a rapid return towards baseline values thereafter (P = 0.07 for the whole study period); in contrast, green tea had no effect. Both black and green tea increased augmentation index (by 5.0% and by 6.6%, P < 0.01 and P < 0.001, respectively) throughout the study. These changes were less than the respective changes produced by caffeine. Both black and green tea had a significant pressor effect. No change in oxidant status was found with both types of tea. CONCLUSIONS: Both black and green tea increases acutely wave reflections and only black tea increases aortic stiffness. Tea flavonoids may play a role in the attenuation of the effects of caffeine contained in tea.

Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease.

BACKGROUND: It has been shown that acute intake of red wine improves endothelial-dependent vasodilatation. It is not clear, however, which constituents of red wine are responsible for this effect. We examined whether acute intake of a red grape polyphenol extract has a positive effect on brachial artery flow-mediated dilatation. METHODS: We recruited 30 male patients with coronary heart disease. They were randomly assigned either to a red grape polyphenol extract (600 mg) dissolved in 20 ml of water (n = 15) or 20 ml of water (placebo) (n = 15). The extract of grapes contained 4.32 mg epicatechin, 2.72 mg catechin, 2.07 mg gallic acid, 0.9 mg trans-resveratrol, 0.47 mg rutin, 0.42 mg epsilon-viniferin, 0.28 mg, p-coumaric acid, 0.14 mg ferulic acid and 0.04 mg quercetin per gram. Flow-mediated dilatation of the brachial artery was evaluated after reactive hyperemia induced by cuff obstruction of the forearm, using high-resolution ultasonography. Particularly, flow-mediated dilatation was measured after fasting and 30, 60 and 120 min after the intake of the grape extract or placebo. RESULTS: Intake of the red grape polyphenol extract caused an increase in flow-mediated dilatation, peaking at 60 min, which was significantly higher than the baseline values (4.52+/-1.34 versus 2.6+/-1.5%; P < 0.001) and the corresponding values at 60 min after the intake of placebo (4.52+/-1.34 versus 2.64+/-1.8%, P < 0.001). There was no change in FMD values after the intake of placebo throughout the whole duration of the study. CONCLUSION: Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. These results could probably, at least partly, explain the favorable effects of red wine on the cardiovascular system.