stilbenes and Cerebrovascular-Disorders

Resveratrol-a natural polyphenolic compound-was first discovered in the 1940s. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. A large part of these effects are related to its antioxidant properties. Here we review: (a) the sources, the metabolism, and the bioavailability of resveratrol; (b) the ability of resveratrol to modulate redox signalling and to interact with multiple molecular targets of diverse intracellular pathways; (c) its protective effects against oxidative damage in cardio-cerebro-vascular districts and metabolic disorders such as diabetes; and (d) the evidence for its efficacy and toxicity in humans. The overall aim of this review is to discuss the frontiers in the field of resveratrol's mechanisms, bioactivity, biology, and health-related use.

Topics: Antioxidants; Biological Availability; Cardiovascular Diseases; Cerebrovascular Disorders; Clinical Trials as Topic; Diabetes Mellitus; Humans; Metabolic Diseases; Oxidation-Reduction; Oxidative Stress; Resveratrol; Stilbenes

Resveratrol is a polyphenol present in grapes, some nuts and dried fruits, and red wine. A number of beneficial properties have been attributed to this compound. Its potential neuroprotective effects are the subject of much research today.. To review the effects of resveratrol, and more particularly those related to its capacity to offer protection against the neurodegeneration associated with several pathologies and traumatic injuries in the central nervous system.. It has been suggested that the daily consumption of red wine, and therefore of resveratrol, could account for the so-called 'French paradox', according to which the population in the south of France, despite eating a diet that is relatively high in saturated fats, presents a low risk of heart disease. From this first evidence of the cardioprotective properties of resveratrol, its study has been extended and equally attractive biopharmacological effects have now been found in many different fields. Thus, neuroprotective effects have been found in models of neurodegeneration (Alzheimer's, Parkinson's or Huntington's disease, or diverse neuropathies), of ischaemia and of brain and spinal cord injury, but further clinical data are still needed in this regard.. Although few studies have been conducted in humans, recent findings in experimental models of neurological pathology are encouraging and open up the doors to future clinical studies that will allow the therapeutic value of resveratrol to be determined.

Topics: Amyloid beta-Peptides; Animals; Antioxidants; Biological Availability; Cardiotonic Agents; Cell Survival; Cerebrovascular Disorders; Diet, Mediterranean; DNA Repair; Humans; Nerve Tissue Proteins; Neurodegenerative Diseases; Neuroprotective Agents; Peripheral Nervous System Diseases; Reperfusion Injury; Resveratrol; Sirtuin 1; Spinal Cord; Stilbenes; Trauma, Nervous System; Vitis; Wine

The 'French Paradox' has been typically associated with moderate consumption of wine, especially red wine. A polyphenol 3,4',5-trihydroxy-trans-stilbene (a member of the non-flavonoids family), better known as resveratrol, has been purported to have many health benefits. A number of these valuable properties have been attributed to its intrinsic antioxidant capabilities, although the potential level of resveratrol in the circulation is likely not enough to neutralize free radical scavenging. The brain and the heart are uniquely vulnerable to hypoxic conditions and oxidative stress injuries. Recently, evidence suggests that resveratrol could act as a signaling molecule within tissues and cells to modulate the expression of genes and proteins. Stimulation of such proteins and enzymes could explain some the intracellular antioxidative properties. The modulation of genes could suffice as an explanation of some of resveratrol's cytoprotective actions, as well as its influence on blood flow, cell death, and inflammatory cascades. Resveratrol stimulation of the expression of heme oxygenase is one example. Increased heme oxygenase activity has led to significant protection against models of in vitro and in vivo oxidative stress injury. Resveratrol could provide cellular resistance against insults; although more work is necessary before it is prescribed as a potential prophylactic in models of either acute or chronic conditions, such as stroke, amyotrophic lateral sclerosis, Parkinson, Alzheimer, and a variety of age-related vascular disorders.

Topics: Animals; Antioxidants; Cerebrovascular Disorders; Encephalitis; Flavonoids; Gene Expression Regulation, Enzymologic; Heme Oxygenase (Decyclizing); Humans; Neurodegenerative Diseases; Neuroprotective Agents; Oxidative Stress; Phenols; Polyphenols; Resveratrol; Stilbenes

Progressive microvascular dysfunction in type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to brain regions during local metabolic demand, thereby increasing risks of dementia. Having previously demonstrated that resveratrol can enhance vasodilator function in the systemic circulation, we hypothesised that resveratrol could similarly benefit the cerebral circulation. We aimed to determine the most efficacious dose of resveratrol to improve cerebral vasodilator responsiveness (CVR) in T2DM.. In a double-blind, placebo-controlled, balanced crossover intervention, 36 dementia-free, non-insulin dependent T2DM older adults (49-78 years old) consumed single doses of synthetic trans-resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to assess CVR to a hypercapnic stimulus, both before and 45 min after treatment. CVR, measured bilaterally in the middle cerebral arteries (MCA) and posterior cerebral arteries (PCA), was expressed as the percentage change in mean blood flow velocity from baseline to the peak velocity attained during hypercapnia. Resveratrol consumption increased CVR in the MCA; mean within-individual changes for each dose from placebo were 13.8 ± 3.5% for 75 mg (P = 0.001), 8.9 ± 3.5% for 150 mg (P = 0.016), and 13.7 ± 3.3% for 300 mg (P < 0.001); only the 75 mg dose was efficacious in the PCA (13.2 ± 4.5%, P = 0.016).. Our results provide the first clinical evidence of an acute enhancement of vasodilator responsiveness in cerebral vessels following consumption of resveratrol in this population who are known to have endothelial dysfunction and sub-clinical cognitive impairment. Importantly, maximum improvement was observed with the lowest dose used.. ACTRN12614000891628 (www.anzctr.org.au).

Topics: Aged; Blood Flow Velocity; Cerebrovascular Circulation; Cerebrovascular Disorders; Cognition; Cognition Disorders; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Middle Cerebral Artery; Posterior Cerebral Artery; Resveratrol; Stilbenes; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Transcranial; Vasodilation; Victoria

Polygonum cuspidatum is a potent anti-oxidant herb that is well known for its various bioactivities. The current study investigates which compound group is most effective, to establish the key compound groups for quality assessment, especially in terms of neuroprotective effects. The roots of P. cuspidatum were extracted with 85% methanol and fractionated with hexane, ethyl acetate, n-butanol and water. Each fraction was applied to an in vitro radical scavenging assay, a lipid peroxidation assay in brain homogenates and an in vivo assay using a transient focal cerebra ischemia model induced by a middle cerebral artery occlusion in a Sprague-Dawley rat. The ethyl acetate fraction was the most effective fraction in both in vitro and in vivo assays, having the highest stilbene and anthraquinone contents. These results suggest that stilbenes and anthraquinones may be key compound groups for the quality assessment of the anti-oxidative and neuroprotective effects of P. cuspidatum.

Topics: 1-Butanol; Acetates; Animals; Anthraquinones; Cerebrovascular Disorders; Chemical Fractionation; Chromatography, High Pressure Liquid; Fallopia japonica; Hexanes; Lipid Peroxidation; Male; Neuroprotective Agents; Phytotherapy; Plant Extracts; Plant Roots; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Rotarod Performance Test; Stilbenes