stilbenes and Carotid-Stenosis

In patients with carotid stenosis, the risk of plaque rupture is related to the composition of the atherosclerotic plaque rather than to its magnitude. In this regard, we evaluated the effects of a supplement, Aterofisiol,(®) containing omega-3 (EPA [eicosapen acid] DHA [docosahexaenoic acid]), vitamin K2, vitamin B6, vitamin B12, oligomeric proanthocyanidins (OPC) and resveratrol on the composition of atherosclerotic plaque and on neurological symptoms in patients with carotid stenosis undergoing carotid endarterectomy.. The study was randomized, prospective, and double-blinded. Eligible patients were of both sexes, with carotid stenosis >70% who underwent endarterectomy. Enrolled patients were randomly allocated to receive either one tablet of acetylsalicylic acid 100 mg (Cardioaspirin(®)) + one tablet of Aterofisiol every 24 hours or one tablet of Cardioaspirin + one tablet of placebo every 24 hours. Each treatment was started 30 days before the surgery and was stopped 5 days before the surgery. The plaques were removed "en bloc" using standard surgical technique.. During the study period, 214 patients (135 men and 79 women) were enrolled for intent-to-treat and randomized in two groups: Group A: 107 patients (68 men and 39 women) were treated with Cardioaspirin + Aterofisiol. Group B: 107 patients (67 men and 40 women) were treated with Cardioaspirin + placebo. At the end of the study, 202 patients participated fully (103 patients in Group A and 99 patients in Group B), making up the protocol evaluation population (94.4%). The mean lipid content of removed plaques was significantly lower (P<0.05) in Group A. We recorded a significantly lower incidence of neurological symptoms in Group A in comparison with Group B (P<0.05).. In the study, Aterofisiol showed to be effective in reducing the amounts of cholesterol and lipids in the plaques and in reducing adverse neurological events in the study group with respect to controls.

Topics: Adult; Aged; Aspirin; Carotid Stenosis; Dietary Supplements; Double-Blind Method; Endarterectomy, Carotid; Fatty Acids, Omega-3; Female; Humans; Male; Middle Aged; Plaque, Atherosclerotic; Proanthocyanidins; Prospective Studies; Resveratrol; Stilbenes; Vitamins

Dementia is the most prevalent neurological disease in aged people. Chronic cerebral hypoperfusion (CCH) is one of the causes of vascular dementia (VaD) and is also an etiological factor for Alzheimer's disease (AD). However, effective therapy for those two diseases is still missing. Resveratrol is a polyphenol produced by plants that have multiple biological functions, such as increased life span and delay in the onset of diseases associated with aging. It is known supplement with resveratrol could exert neuroprotection against multiple injury factors induced neuronal death and degeneration, as well as the cognitive decline of CCH rat model.. The morris water maze was used to evaluate the learning and memory, electrophysiological recording was used to detect the synaptic plasticity, the Golgi staining was used to examine the change of dendritic spines, the western blot was used to detect the proteins levels.. We reported that resveratrol pretreatment effectively restore the synaptic plasticity in CCH rats both functional and structural. We also found that the PKA-CREB activation may be a major player in resveratrol-mediated neuroprotection in CCH model.. Our data provide the mechanistic evidence for the neuroprotective effects of resveratrol in vascular dementia.

Topics: Animals; Carotid Stenosis; Cerebrovascular Circulation; Chronic Disease; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Dementia, Vascular; Dendritic Spines; Dentate Gyrus; Enzyme Activation; Hypoxia-Ischemia, Brain; Learning Disabilities; Long-Term Potentiation; Male; Maze Learning; Memory Disorders; Nerve Tissue Proteins; Neuroprotective Agents; Random Allocation; Rats; Rats, Wistar; Resveratrol; Stilbenes

Resveratrol (Resv), a red wine polyphenol, is known to exhibit vascular protective effects and reduce vascular smooth muscle cell mitogenesis. Vascular smooth muscle cell proliferation is a critical factor in the pathogenesis of restenosis, the renarrowing of vessels that often occurs after angioplasty and/or stent implantation. Although Resv has been shown to be an estrogen receptor (ER) modulator, the role of the ER in Resv-mediated protection against restenosis has not yet been elucidated in vivo. Therefore, with the use of a mouse carotid artery injury model, our objective was to determine the role of ER in modulating Resv-mediated effects on neointimal hyperplasia. Female wild-type and ER-α(-/-) mice were administered a high-fat diet ± Resv for 2 wk. A carotid artery endothelial denudation procedure was conducted, and the mice were administered a high-fat diet ± Resv for an additional 2 wk. Resv-treated wild-type mice exhibited a dramatic decrease in restenosis, with an increased arterial nitric oxide (NO) synthase (NOS) activity and NO production. However, in the ER-α(-/-) mice, Resv failed to afford protection and failed to increase NO production, apparently because of a decreased availability of the NOS cofactor tetrahydrobiopterin. To verify the role of NO in Resv-mediated effects, mice were coadministered Resv plus a nonselective NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME). Cotreatment with l-NAME significantly attenuated the antirestenotic properties of Resv. These data thus suggest that Resv inhibits vascular proliferative responses after injury, predominately through an ER-α-dependent increase in NO production.

Topics: Animals; Carotid Arteries; Carotid Stenosis; Cell Proliferation; Disease Models, Animal; Enzyme Inhibitors; Estrogen Receptor alpha; Female; Mice; Mice, Knockout; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Resveratrol; Secondary Prevention; Stilbenes

An emulsion system composed of vitamin E, coconut oil, soybean phosphatidylcholine, non-ionic surfactants, and polyethylene glycol (PEG) derivatives (referred to as the tocol emulsion) was characterized in terms of its physicochemical properties, drug release, in vivo efficacy, toxicity, and stability. Systems without vitamin E (referred to as the lipid emulsion) and without any oils (referred to as the aqueous micelle system) were prepared for comparison. A lipophilic antioxidant, resveratrol, was used as the model drug for emulsion loading. The incorporation of Brij 35 and PEG derivatives reduced the vesicle diameter to <100nm. The inclusion of resveratrol into the emulsions and aqueous micelles retarded the drug release. The in vitro release rate showed a decrease in the order of aqueous micelle system>tocol emulsion>lipid emulsion. Treatment of resveratrol dramatically reduced the intimal hyperplasia of the injured vascular wall in rats. There was no significant difference in this reduction when resveratrol was delivered by either emulsion or the aqueous micelle system. The percentages of erythrocyte hemolysis by the emulsions and aqueous micelle system were approximately 0 and approximately 10%, respectively. Vitamin E prevented the aggregation of emulsion vesicles. The mean vesicle size of the tocol emulsion remained unchanged during 30 days at 37 degrees C. The lipid emulsion and aqueous micelle system, respectively, showed 11- and 16-fold increases in vesicle size after 30 days of storage.

Topics: Animals; Antioxidants; Biphenyl Compounds; Carotid Stenosis; Chemistry, Pharmaceutical; Coconut Oil; Disease Models, Animal; Drug Carriers; Drug Compounding; Emulsions; Hemolysis; Male; Micelles; Oils; Particle Size; Phosphatidylcholines; Picrates; Plant Oils; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Resveratrol; Solubility; Stilbenes; Surface-Active Agents; Technology, Pharmaceutical; Time Factors; Vitamin E