The complex blood circulation that the cardiovascular system maintains is essential for providing cells with nutrition and oxygen while expelling waste. A serious hazard to world health, cardiovascular illnesses are a collection of diseases that affect the heart and blood arteries. Since heart disease affects over half of all individuals in the United States, it is critical to comprehend its origins, treatments, and preventative actions.
Cardiovascular Disorders: Causes and Treatments
By 2030, it is projected that the rising incidence of cardiovascular illnesses (CVDs), which include hypertension, atherosclerosis, stroke, ischemic heart disease, and heart failure, will be a factor in more than 23.6 million CVD-related deaths worldwide. One plant-based, non-flavonoid polyphenolic molecule that may protect against CVD is resveratrol (RES). It is found in large amounts in red wine and grapes. The "French paradox," which notes that despite eating a diet high in saturated fats and moderate red wine consumption, the French population has a comparatively low prevalence of cardiovascular diseases (CVDs), is the basis for the idea.
This contradiction may be explained by the combined impact of polyphenols rather than just RES, yet RES is unique in that it protects arterial walls by inhibiting oxidation, inflammation, platelet oxidation, and thrombus formation. Red wine has lower amounts of RES than high-dose RES supplements, which makes it difficult to understand the results of research investigations. Although there is a growing corpus of research on RES, few of these studies deal with human clinical trials, highlighting the need for long-term, well-regulated trials to confirm RES's potential advantages in the fight against CVDs.
Atherosclerosis, or the accumulation of fatty plaques in the arteries, is a prominent cause of illnesses like coronary artery disease, however, there are other causes of cardiovascular problems as well. The development of these problems is facilitated by risk factors such as diabetes, high blood pressure, high cholesterol, obesity, smoking, poor nutrition, and lack of exercise. The spectrum of treatment approaches includes dietary and activity modifications, blood thinners, cholesterol-lowering medicines, and, in extreme situations, surgery.
In order to effectively manage cardiovascular diseases, prevention is essential. This includes both primary and secondary prevention. Reducing the burden of these conditions involves a combination of lifestyle modifications, early identification, routine check-ups, and adherence to recommended treatment regimens. Research emphasizes the significance of customized strategies to reduce risk factors and concentrates on primary prevention, health services, clinical recommendations, and epidemiology in developing nations where cardiovascular diseases are a significant public health problem.
Resveratrol
Natural polyphenol resveratrol is present in red wine, grapes, and other plant sources. It has drawn a lot of interest because it may help obese people lose weight and control their Type 2 Diabetes Mellitus (T2DM). We shall examine resveratrol's physiological function, advantages, and effects on obesity and type 2 diabetes in this post. We will also go over the results of pre-clinical and clinical studies that provide insight into resveratrol's potential as a treatment for certain ailments.
A stilbenoid is a polyphenolic molecule that includes resveratrol. Plants naturally produce it in response to a variety of stresses, including damage, fungal infections, and UV radiation exposure. Due to its correlation with red wine and the "French Paradox," which describes the minimal risk of heart disease among French people while eating a diet high in saturated fats, resveratrol has gained significant interest. Resveratrol helps plants become more resilient overall by acting as a shield against environmental stresses. Resveratrol has anti-ageing, anti-inflammatory, and antioxidant effects in animals. Its capacity to activate sirtuins, a family of proteins essential for controlling several cellular functions, is thought to be the cause of these effects [1].
Benefits
Numerous health advantages of resveratrol have been studied scientifically, including:
· Antioxidant Properties: Resveratrol functions as an antioxidant to shield cells from free radical-induced oxidative damage. Its capacity to prevent different illnesses and have anti-ageing benefits may be attributed to this feature.
· Anti-Inflammatory Effects: Research has shown that resveratrol has anti-inflammatory qualities, which lower inflammation and the chance of chronic illnesses linked to it.
· Cardiovascular Health: By encouraging blood vessel dilatation, lowering blood pressure, and preventing blood clot formation, resveratrol may contribute to improved cardiovascular health.
· Neuroprotective Effects: Research indicates that resveratrol may shield nerve cells from harm, which may help with diseases such as Alzheimer's [2].
Resveratrol and Cardiovascular Health
In the fight for cardiovascular health, resveratrol—a non-flavonoid polyphenol—found in red wine, peanuts, cherries, and grapes is showing promise. Resveratrol provides a multimodal approach to supporting the cardiovascular system, with demonstrated cardiovascular protective benefits that include anti-oxidation, anti-inflammatory responses, antithrombotic characteristics, vasodilation, apoptosis inhibition, and atherosclerosis delay [3].
Clinical research has shown that resveratrol improves diastolic and systolic cardiac functions, vascular function, remodeling, and hypertension. Its function as a metabolic regulatory agent, regulating lipid and glucose metabolism to enhance energy balance and lower cardiovascular risk, is highlighted by a research published in the British Journal of Pharmacology.
Because resveratrol inhibits both oxidative stress and the inflammatory response, it can shield the heart against ischemia and ischemia-reperfusion, two types of cardiac damage. Its promise for treating cardiovascular problems is further supported by human clinical studies that have verified its cardioprotective benefits in people with stable coronary artery disease [4, 5].In diabetic mice, resveratrol was shown to preserve cardiovascular function, with significant benefits shown in mature cardiac cells and cardiac stem/progenitor cell compartments. In diabetic hearts, this impact involves preserving functional capacities, lowering the inflammatory state, and minimizing adverse ventricular remodeling. Ventricular function has significantly recovered as a result. Resveratrol has been demonstrated to improve left ventricular function, reduce cardiac hypertrophy, contractile dysfunction, remodeling, interstitial fibrosis, and plasma BNP levels in heart failure. Resveratrol acts through a variety of molecular processes, including blocking prohypertrophic signaling molecules, improving cardiac Ca2+ handling, triggering prosurvival pathways, and lowering inflammation and oxidative stress.
According to Yan et al., in rats with diabetes-related myocardial infarction, resveratrol functions by inhibiting the production of vascular endothelial growth factor, endothelial nitric oxide synthase, and p38 phosphorylation. Additionally, resveratrol treatment dramatically improves several indices in diabetic rats with myocardial infarction, such as blood glucose, body weight, heart rate, plasma triglyceride levels, and the AST/ALT ratio, while also greatly raising total plasma insulin levels. Indicating less oxidative stress, the therapy also lowers malondialdehyde levels and inflammation-related variables. All these results point to the possibility that resveratrol administration might improve cardiovascular health by increasing vasodilation, avoiding atherosclerosis, and lowering myocardial ischemia-reperfusion damage.
Furthermore, resveratrol causes vasodilation at physiological doses, which lowers blood pressure and the risk of cardiovascular illnesses. Polygonum cuspidatum is a source of resveratrol that has been shown in traditional Chinese medicine to be effective in treating and preventing arteriosclerosis and hyperlipidemia. All things considered, resveratrol's cardiovascular protective benefits are linked to several different molecular targets, which makes it a strong contender for new treatments aimed at atherosclerosis, metabolic syndrome, ischemia/reperfusion, and heart failure.
By targeting important components of the atherosclerotic process, resveratrol (RES) has significant anti-atherosclerotic benefits. By raising HDL cholesterol and lowering LDL and plasma triglyceride levels, it affects lipid profiles. Reducing TNFα production and activating SIRT-1, eNOS, Nrf2, and antioxidant response element (ARE) all contribute to reduced endothelial apoptosis, activation, inflammation, and enhanced endothelial function. Its activities include blocking the production of foam cells, blocking adhesion molecules, and controlling inflammation-related miRNAs. Clinical research on RES has yielded mixed results regarding lipid profiles, but it has also shown promise in decreasing LDL-cholesterol in individuals with type 2 diabetes and plasma triglycerides in various cohorts. Multiple molecular targets are involved in the overall anti-atherosclerotic potential of RES.
Moreover, RES has anti-hypertensive properties that mitigate a significant risk factor for cardiovascular illnesses (CVDs). Preclinical research demonstrates that it effectively lowers blood pressure via endothelium-dependent pathways that enhance the availability of nitric oxide by AMPK, SIRT-1, and Nrf2. Clinical research, notably meta-analyses, confirms that large doses of RES significantly lower blood pressure, especially in people who are hypertensive and dyslipidemic. Better metabolic markers are in line with the anti-hypertensive effect. RES also has protective benefits against ischemic stroke through the maintenance of blood-brain barrier function, inhibition of inflammation and brain damage, and preservation of endothelial function. Preclinical research emphasizes neuroprotective processes, although there hasn't been much clinical research done.
Additionally, RES has promise in preconditioning muscle tissue, modulating platelet aggregation, reducing myocardial ischemia, and maybe even encouraging tissue regeneration. AMPK, eNOS, VEGF activation and the decrease of oxidative stress are among the mechanisms. Clinical trials show a range of results, with RES providing anti-ischemic benefits via a variety of mechanisms, such as the activation of autophagy and the modification of miRNAs. RES's anti-inflammatory and antioxidant characteristics help shield the heart from ischemia-reperfusion damage. All things considered, RES offers a diverse range of therapeutic benefits in the treatment of cardiovascular diseases, including hypertension, atherosclerosis, stroke, and myocardial ischemia [6].
Genes Targeted by Resveratrol
The effects of resveratrol are mediated molecularly through interactions with certain genes and signaling pathways. Most notably, sirtuins—NAD+-dependent deacetylases essential for cellular metabolism and stress response—are activated by resveratrol. The sirtuin family member SIRT1 controls genes linked to oxidative stress, inflammation, and apoptosis, which supports the heart-protective properties of resveratrol.
Additionally, resveratrol affects genes involved in lipid metabolism, increasing the efflux of cholesterol and decreasing the production of cholesterol. Resveratrol further enhances its effect on cardiovascular health by regulating cellular energy metabolism, guarding against oxidative stress, and regulating inflammation and apoptosis through the modulation of signaling pathways such as AMP-activated protein kinase (AMPK) and nuclear factor-kappa B (NF-κB) [7].
In summary, a thorough grasp of the cardiovascular system, its illnesses, and the possible preventive effect of resveratrol offers a more nuanced perspective on cardiovascular health. Given the complexities of gene regulation and the clinical data demonstrating its advantages, resveratrol appears to be a viable therapeutic choice for the treatment and prevention of cardiovascular diseases. Resveratrol's incorporation into cardiovascular treatment may open the door for novel strategies to improve heart health and lower the prevalence of cardiovascular disorders worldwide as research into the topic advances.
Pre-clinical and Clinical Trials of Resveratrol in Cardiovascular Disorders
Resveratrol has been shown in preclinical research to be effective in animal models of heart failure, diabetic cardiomyopathy, hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, and cardiotoxicity from chemotherapy. These investigations have demonstrated that resveratrol protects the cardiovascular system via several different methods, such as anti-oxidation, blocking inflammatory responses, preventing thrombosis, widening blood channels, preventing apoptosis, and postponing atherosclerosis.
Although resveratrol shows potential in treating a variety of cardiovascular disorders, there are currently few clinical investigations on the substance. The majority of resveratrol clinical studies have addressed conditions such as obesity, diabetes, non-alcoholic fatty liver disease (NAFLD), cancer, neurological disorders, and cardiovascular illnesses. Current clinical trials indicate that resveratrol was well tolerated and had a positive effect on disease biomarkers related to cardiovascular illnesses. For instance, resveratrol was reported to provide cardioprotective benefits in people with stable coronary artery disease in a human clinical investigation. According to a different study, resveratrol stopped abnormal heart hypertrophy and contractile dysfunction from occurring.
Nonetheless, several contradictory study outcomes have been made public, highlighting the difficulties in translating promising preclinical discoveries to humans. For instance, resveratrol's effects on certain cancer types were unclear and occasionally even harmful. To completely comprehend the mechanisms of action and possible advantages of resveratrol in cardiovascular diseases, more study is required.
Resveratrol at 500 mg/day for 30 days was given to 48 people (24 males and 24 females) in a randomized parallel trial as part of the research focused on cardiovascular disorders, particularly atherosclerosis, in healthy and slightly overweight persons. The findings indicated a positive rise in serum SIRT1 concentrations but no discernible change in any of the metabolic indices, except an increase in HOMA-IR score, ApoB, and total cholesterol.
Resveratrol supplementation at 150 mg/day for four weeks was the treatment of choice for 40 participants (21 males and 19 females) in a randomized placebo-controlled research about asymptomatic hypercholesterolemics (AHCs) and normohypercholesterolemics (NC) in the setting of cardiovascular illnesses and atherogenesis. With no discernible changes in other lipid markers, the results showed raised vitamin E in AHCs and increased total antioxidant capacity (TAC) in healthy NC persons.
In a four-week randomized, double-blind, placebo-controlled study, 45 individuals (twenty male and twenty female) received a 150 mg daily trans-resveratrol supplement. The experiment was designed to evaluate endothelial function in cardiovascular illnesses in overweight and slightly obese volunteers. On the other hand, endothelial function, inflammation, and glucose and lipid metabolism did not improve, according to the findings [8].
Trans-resveratrol was given at dosages of 125 and 500 mg/day for six months to participants in a randomized, double-blind, placebo-controlled research with 66 participants (45 male, 21 female) who had peripheral arterial disease (PAD) and were 65 years of age or older. The results showed that whereas 500 mg/day did not significantly increase performance on the 6-minute walk test, 125 mg/day produced a statistically significant improvement [8].
A resveratrol-enriched grape extract at 350 mg/day was given for six months to patients in a triple-blind, randomized, placebo-controlled experiment (75 participants, 34 males, 41 females) whose primary goal was to prevent cardiovascular disease. It was shown that there were positive benefits on LDL-C, ApoB, oxidized LDL, and non-HDL-C/ApoB ratio, but no clinically meaningful impacts on thyroid, hepatic, or renal function.
Finally, a research with 27 male volunteers that was randomized, double-blind, placebo-controlled, and focused on healthy older males evaluated the cardiovascular effects of taking a 250 mg daily trans-resveratrol supplement for eight weeks. Exercise training-induced benefits in maximum oxygen uptake, blood pressure, and lipids were eliminated by the supplement, and the results revealed no significant effects on SIRT1 protein concentrations or cardiovascular parameters [8].
Resveratrol may be able to treat cardiovascular diseases, according to data from preclinical and clinical studies. Preclinical research has demonstrated that resveratrol protects the cardiovascular system via several different methods, including anti-oxidation, preventing inflammatory responses, preventing thrombosis, widening blood vessels, preventing apoptosis, and postponing atherosclerosis. Resveratrol was well tolerated and had a positive effect on disease biomarkers in individuals with cardiovascular illnesses, according to clinical studies.
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