The Cardiovascular Nutrapharmacology of Resveratrol: Pharmacokinetics, Molecular Mechanisms and Therapeutic Potential

Abstract

Red wine contains many compounds that may have therapeutic use, including resveratrol (3,4',5-trihydroxytrans-stilbene). Since resveratrol could be administered both in the diet and as a therapeutic agent, defining appropriate concentrations requires understanding of the pharmacokinetics. Resveratrol absorption is rapid but plasma concentrations are low as it is rapidly and efficiently converted into relatively hydrophilic phase-2 conjugates, and metabolites, which are then rapidly excreted via the urine and bile. Resveratrol is an effective antioxidant in vivo by increasing NO synthesis and also maintaining the reduced intracellular redox state via the thioredoxin system. Further, activation of sirtuins (one class of lysine deacetylases) may mediate the cardiovascular responses shown by resveratrol. Studies on animal models of human disease suggest that resveratrol has the potential to decrease cardiovascular symptoms in patients with myocardial infarction, arrhythmias, hypertension, cardiomyopathies, fibrosis, atherosclerosis, thrombosis and diabetes, but, as yet, human clinical trials are rare. Cardioprotection by resveratrol in rodent models may rely on mechanisms producing pharmacological preconditioning in the heart including reducing reactive oxygen species, improving vasorelaxation and angiogenesis, preventing inflammation and apoptosis, delaying atherosclerosis as well as decreasing cardiovascular remodelling. Interventional studies in humans need to be completed before resveratrol can be considered as a standard therapeutic agent. Therefore, future studies should focus on obtaining the level of evidence required to determine whether resveratrol can be added to the list of evidence-based therapies for cardiovascular diseases that includes renin-angiotensin system inhibitors, beta-adrenoceptor antagonists and calcium entry blockers.

Role of membrane dynamics processes and exogenous molecules in cellular resveratrol uptake: Consequences in bioavailability and activities

“…Among these bioactive compounds, several studies [1] revealed that resveratrol (trans-3,4 0 ,5-trihydroxystilbene; RSV) may be one of the main wine microcomponents responsible for health benefits. Indeed, RSV possesses a myriad of beneficial effects and can act at multiple levels, such as cellular signalling, enzymatic pathways, apoptosis and gene expression [2][3][4]. Although the biological positive effects of RSV are largely elucidated, little is known about the transport and the distribution of RSV throughout the body.…”

Anti-Inflammatory and Antioxidant Effects of Resveratrol in Healthy Smokers A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial

“…It exists in two isoforms, trans-resveratrol and cis-resveratrol, and the trans-98 isomer is the more stable form [6]. A growing number of in vitro and animal studies have evaluated the 99 beneficial properties of resveratrol [7][8][9]. The following activities have been identified for resveratrol: 100 antioxidant, anti-inflammatory, anti-carcinogenic, anti-platelet aggregation, cardio-protective, neuro-protective, 101 cartilage-protective, anti-aging activities.…”

“…The following activities have been identified for resveratrol: 100 antioxidant, anti-inflammatory, anti-carcinogenic, anti-platelet aggregation, cardio-protective, neuro-protective, 101 cartilage-protective, anti-aging activities. In addition, this compound has been shown to increase lifespan, act as 102 an insulin sensitizer, reduce body weight, improve endothelial function, and mimic calorie restriction [7][8][9][10].…”

Newly-Recognized Small Molecule Receptors on Human Breast Cancer Cell Integrin αvβ3 that Affect Tumor Cell Behavior

“…Identification of the resveratrol receptor on the integrin of breast cancer cells and other solid tumor cells may provide useful insights into the actions of this stilbene. The rapid cellular uptake and metabolism of resveratrol (Kroon et al, 2010)-leading to pharmacokinetic and pharmacodynamic speculation about the relative bioactivity of resveratrol analogues-is less puzzling if, in fact, the parent compound (resveratrol) can act on the outside of the cell. That is, resveratrol binds to the integrin and rapidly initiates a MAPK-requiring, p53-dependent apoptotic process, regardless of uptake of the compound and chemical processing.…”