Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effect of resveratrol (3,4',5-trihydroxy stilbene), a phenolic compound found in the skins of most grapes, on blood pressure and bone loss in ovariectomized (OVX), stroke-prone spontaneously hypertensive rats (SHRSP). Nineteen-week-old female SHRSP were divided into a sham-ovariectomized (sham) group fed a control diet and two OVX groups fed either a control diet (OVX-Cont) or a diet supplemented with resveratrol (5 mg/kg per d; OVX-Resv). Ovariectomy induced significant increases in systolic blood pressure (SBP). Resveratrol lowered the SBP by 15%) by the third week of administration, and this effect was maintained throughout the study. Resveratrol treatment also significantly enhanced endothelium-dependent vascular relaxation in response to acetylcholine (ACh) in OVX rats. Finally, femur breaking energies measured for the resveratrol-treated (OVX-Resv) group were significantly higher than those of the resveratrol-untreated (OVX-Cont) group. While no significant differences in calcium, magnesium and phosphorus content were found between the femurs of OVX-Cont and OVX-Resv rats, the femur hydroxyproline content in the OVX-Resv group was significantly higher than of the OVX-Cont group. We conclude that, in OVX-SHRSP, resveratrol acts by a similar mechanism to mammalian estrogens, lowering blood pressure by increasing dilatory responses to ACh. The present study also demonstrated that resveratrol was able to prevent ovariectomy-induced decreases in femoral bone strength.
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PMID:Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats. 1088 94

Advanced glycation end-products (AGEs) of plasma proteins and/or matrix proteins are candidate mediators for various vascular complications such as atherosclerosis. We previously reported a significantly larger accumulation of AGEs of the aorta in stroke-prone spontaneously hypertensive rats (SHRSP) than in age-matched Wistar-Kyoto rats (WKY). In this study, we examined the effects of AGEs on vascular smooth muscle cells (VSMC) from SHRSP and WKY rats. We also studied the in vitro effects of resveratrol (3, 4',5-trihydroxystilbene), a natural phytestrogen, on VSMC proliferation, DNA synthesis, and collagen synthesis activity in SHRSP-VSMC. AGEs accelerated the proliferation of SHRSP- or WKY-VSMC in a time- and dose-dependent manner. VSMC from SHRSP were more sensitive to AGEs than VSMC from normotensive WKY. AGEs also significantly increased DNA synthesis and prolyl hydroxylase activity, a marker for collagen synthesis, in SHRSP-VSMC. AGEs-induced increases in TGF-beta1 mRNA in SHRSP-VSMC were significantly greater than in WKY-VSMC. Resveratrol inhibited AGEs-stimulated proliferation, DNA synthesis, and prolyl hydroxylase activity in SHRSP-VSMC in a dose-dependent manner. ICI 182780, a specific estrogen receptor antagonist, partly blocked the inhibitory effects of resveratrol on AGEs-stimulated proliferation, DNA synthesis, and prolyl hydroxylase activity. Resveratrol significantly inhibited AGEs-induced TGF-beta1 mRNA increases in a dose-dependent manner. Thus, resveratrol may confer protective effects on the cardiovascular system by attenuating vascular remodeling and may be clinically useful as a safer substitute for feminizing estrogens in preventing cardiovascular disease.
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PMID:Resveratrol inhibits AGEs-induced proliferation and collagen synthesis activity in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. 1090 96

Resveratrol and trans-resveratrol are powerful phytoestrogens, present in the skins of grapes and other plant foods and wine, which demonstrate a broad spectrum of pharmacological and therapeutic health benefits. Phytoestrogens are naturally occurring plant-derived nonsteroidal compounds that are functionally and structurally similar to steroidal estrogens, such as estradiol, produced by the body. Various studies, reviewed herein, have demonstrated the health benefits of phytoestrogens in addressing climacteric syndrome including vasomotor symptoms and postmenopausal health risks, as well as their anticarcinogenic, neuroprotective and cardioprotective activities and prostate health and bone formation promoting properties. Conventional HRT drugs have been demonstrated to cause serious adverse effects including stroke and gallbladder disease, as well as endometrial, uterine and breast cancers. Recent research demonstrates that trans-resveratrol binds to human estrogen receptors and increases estrogenic activity in the body. We investigated the effects of protykin, a standardized extract of trans-resveratrol from Polygonum cuspidatum, on cardioprotective function, the incidence of reperfusion-induced arrhythmias and free radical production in isolated ischemic/reperfused rat hearts. The rats were orally treated with two different daily doses of protykin for 3 weeks. Coronary effluents were measured for oxygen free radical production by electron spin resonance (ESR) spectroscopy in treated and drug-free control groups. In rats treated with 50 and 100 mg/kg of protykin, the incidence of reperfusion-induced ventricular fibrillation was reduced from its control value of 83% to 75% (p < 0.05) and 33% (p < 0.05), respectively. Protykin was seen to possess cardioprotective effects against reperfusion-induced arrhythmias through its ability to reduce or remove the reactive oxygen species in ischemic/reperfused myocardium. Taken together, these data suggest that trans-resveratrol supplementation may be a potential alternative to conventional HRT for cardioprotection and osteoporosis prevention and may confer other potential health benefits in women.
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PMID:Benefits of resveratrol in women's health. 1195 81

Polyphenolic compounds, such as resveratrol, are naturally present at high concentration in grape skin, seeds, and red wine. Resveratrol is present in cis and trans isoforms and the major trans isomer is the biologically active one. Epidemiologic studies have revealed a reduced incidence of cardiovascular risk associated with consumers of red wine; this has been popularized as the French paradox. Resveratrol has been shown to have significant antioxidant properties in a variety of in vitro and in vivo models. It can reduce ischemic damage in heart ischemia reperfusion injury and also in brain ischemia/reperfusion in rodent models. Due to the high rate of oxygen consumption in the brain, and especially low levels of antioxidant defense enzymes, this organ is particularly susceptible of free radical damage. Most of the protective biological actions associated with resveratrol have been associated with its intrinsic radical scavenger properties. We have investigated the possibility of other indirect pathways by which resveratrol can exert its neuroprotective abilities. We have specifically tested whether heme oxygenase neuroprotective enzyme could be stimulated after resveratrol treatment. Using primary neuronal cultures, resveratrol was able to significantly induce heme oxygenase 1, whereas vehicle control showed no effect. No detectable toxicity was quantified. It is well established that after stroke significant levels of intracellular heme levels increase. The source of free heme comes mainly from several heme-containing enzymes. Heme (iron-protoporphyrin IX) is a pro-oxidant and its rapid degradation by heme oxygenase is believed to be protective. Moreover, the generation of heme metabolites can also have their own intrinsic cellular properties. All together, increased heme oxygenase activity by resveratrol is a unique pathway by which this compound can exert its neuroprotective actions.
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PMID:Potential mechanism by which resveratrol, a red wine constituent, protects neurons. 1285 18

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.
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PMID:Unique properties of polyphenol stilbenes in the brain: more than direct antioxidant actions; gene/protein regulatory activity. 1595 15

Recent studies in a variety of species including mammals showed that resveratrol (trans-3, 5, 4''-trihydroxystibene) treatment and caloric restriction increased silent information regulator 2/sirtuin 1 activity, which mediated increase in life span/cell survival. Resveratrol is a naturally occurring phytoalexin and a well-documented cardioprotective agent. Similarly, ischemic preconditioning (IPC) has been shown to be both cardio- and cerebroprotective against subsequent ischemic insults. A major emphasis in this field is to understand the molecular mechanisms that mediate this phenomenon. The goal of this study was to define whether resveratrol can emulate IPC neuroprotection against cerebral ischemia. Employing an in vitro model of cerebral ischemia, the organotypic hippocampal slice culture, we report that resveratrol pretreatment mimics IPC via the SIRT1 pathway. Blockade of SIRT1 activation by sirtinol after IPC or resveratrol pretreatment abolished their neuroprotection. A better understanding of the mechanisms by which resveratrol induces ischemic tolerance in a prophylactic manner may provide a novel therapy against stroke or neurosurgical procedures.
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PMID:Resveratrol mimics ischemic preconditioning in the brain. 1639 77

We have studied some hemodynamic parameters as heart rate (HR) developed pressure (DP) and maximal positive values of the first derivative of pressure (+dP/dt max) in isolated heart from control or resveratrol treated rats. In acute ex vivo experiments, resveratrol (1-100 microM) infusion in Langendorff perfused hearts did not affect contractile function in either normoxic conditions or after ischemia/reperfusion. However when semi-chronically administered by IP injection during 7 days, resveratrol which had no effect on pre-ischemic heart greatly improved post-ischemic indexes of myocardial function. Resveratrol effect is dose-dependent and seemed optimal at a plasma level of 18.5 microM. This concentration is very close to that previously shown to be optimal and non-toxic by others. These beneficial effects of resveratrol are only partly explained by its antioxidant properties as suggested by the lack of any dose-response effect on tissue malondialdehyde (MDA) levels. They are also clearly not mediated by nitric oxide (NO) elevation. When acutely infused resveratrol had no beneficial effect and therefore could not be proposed in acute scenarios of ischemia/reperfusion or stroke. However resveratrol appeared as an efficient and promising molecule in the prevention of heart dysfunction.
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PMID:Strong cardioprotective effect of resveratrol, a red wine polyphenol, on isolated rat hearts after ischemia/reperfusion injury. 1712 27

Resveratrol (trans-3,4',5-trihydroxystilbene) is a natural phytoalexin found in grape skin, and has been suggested to be an antioxidant agent, an anticancer agent and a cardioprotective agent. In particular, recent experimental evidence has demonstrated that resveratrol exhibits neuroprotective effects in various assay systems. During the study on the resveratrol derivatives, we found that (4-methoxybenzylidene)-(3-methoxyphenyl)amine (MBMPA), which has blocked free phenolic groups, strongly protects neuronal cells against ischemic damage on a higher activity than resveratrol. The MBMPA potently reduced the level of neuronal cell death in an oxygen and glucose deprivation-exposed rat organotypic hippocampal slice culture. In addition, ATP depletion following the onset of oxygen and glucose deprivation in an adult hippocampal slice was blocked by the MBMPA treatment. These results suggest that MBMPA has a neuroprotective effect on an in vitro ischemia model, and may be useful for treating stroke.
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PMID:Protective effect of (4-methoxybenzylidene)-(3-methoxynophenyl)amine against neuronal cell death induced by oxygen and glucose deprivation in rat organotypic hippocampal slice culture. 1720 85

Resveratrol, a natural polyphenolic compound, is found in a few edible materials and is well known for its phytoestrogenic and antioxidant properties. A growing body of in vivo and in vitro evidence indicates that resveratrol has protective effect on cerebral ischemic stroke. Here, we review the effect of resveratrol on cerebral ischemic stroke, and propose a possible mechanism. During acute phases after stroke, resveratrol preconditioning suppresses matrix metalloprotease-9 activity to ameliorate blood-brain barrier disruption, edema formation and neuronal cell death caused by ischemia and reperfusion. But during delayed phases after stroke, resveratrol preconditioning conduces to cerebral angiogenesis and brain regeneration through increasing matrix metalloprotease-9 activity and expression. Resveratrol's effect on matrix metalloprotease-9 is distinguishing in different phases because of temporal and spatial redistribution of matrix metalloprotease-9 within the cells of the neurovascular unit after cerebral ischemia. This paper also hypothesizes that resveratrol treatment after cerebral ischemia might be beneficial for cerebral angiogenesis and brain regeneration during delayed phases after stroke.
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PMID:New insights into mechanism for the effect of resveratrol preconditioning against cerebral ischemic stroke: Possible role of matrix metalloprotease-9. 1760 79

A previous study from our lab has shown that the polyphenol-rich pomegranate juice can protect the neonatal mouse brain against hypoxic-ischemic (H-I) injury when given to mothers in their drinking water. To test the hypothesis that this protection is due to the polyphenols in the juice, we studied the effects of the pomegranate polyphenol extract in the same neonatal H-I model. To further explore the role of a specific polyphenol in neonatal H-I we investigated the effects of resveratrol. The neuroprotective effects of resveratrol have been demonstrated in adult models of stroke, but had not previously been examined in neonates. We show that pomegranate polyphenols and resveratrol reduce caspase-3 activation following neonatal H-I. Resveratrol reduced caspase-3 activation when given before the injury but not when given 3 h after the injury. In addition to preventing caspase-3 activation, resveratrol also reduced calpain activation. Finally, we show that resveratrol can protect against tissue loss measured at 7 days after the injury. These and other recent findings suggest that polyphenols should be further investigated as a potential treatment to decrease brain injury due to neonatal H-I.
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PMID:Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury. 1776 4


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