Showing papers by "Dipak K. Das published in 2011"

What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

Abstract: Background: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingor, Denmark. Methodology: Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1 Can resveratrol be recommended in the prevention or treatment of human diseases?; 2 Are there observed ‘‘side effects’’ caused by the intake of resveratrol in humans?; 3 What is the relevant dose of resveratrol?; 4 What valid data are available regarding an effect in various species of experimental animals?; 5 Which relevant (overall) mechanisms of action of resveratrol have been documented? Conclusions/Significance: The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.

Resveratrol in cardiovascular health and disease.

Abstract: Resveratrol, initially used for cancer therapy, has shown beneficial effects against most degenerative and cardiovascular diseases from atherosclerosis, hypertension, ischemia/reperfusion, and heart failure to diabetes, obesity, and aging. The cardioprotective effects of resveratrol are associated with its preconditioning-like action potentiated by its adaptive response. During preconditioning, small doses of resveratrol can exert an adaptive stress response, forcing the expression of cardioprotective genes and proteins such as heat shock and antioxidant proteins. Similarly, resveratrol can induce autophagy, another form of stress adaptation for degrading damaged or long-lived proteins, as a first line of protection against oxidative stress. Resveratrol's interaction with multiple molecular targets of diverse intracellular pathways (e.g., action on sirtuins and FoxOs through multiple transcription factors and protein targets) intertwines with those of the autophagic pathway to give support in the modified redox environment after stem cell therapy, which leads to prolonged survival of cells. The successful application of resveratrol in therapy is based upon its hormetic action similar to any toxin: exerting beneficial effects at lower doses and cytotoxic effects at higher doses.

Cardioprotection by Endoplasmic Reticulum Stress–Induced Autophagy

Abstract: This study tested the hypothesis that the induction of autophagy by producing therapeutic amounts of endoplasmic reticulum (ER) stress in the heart before an ischemic insult would ameliorate/reduce subsequent lethal myocardial ischemic/reperfusion (I/R) injury (similar to ischemic preconditioning). A dose–response study with both tunicamycin and thapsigargin was performed to determine the optimal dose (0.3 mg/kg) for inducing autophagy for cardioprotection. The Sprague–Dawley rats weighing between 250 and 300 g were randomly assigned into five groups: normal control (injected with saline only), high (3 mg/kg), and low (0.3 mg/kg) doses of tunicamycin or thapsigargin, respectively. After 48 h, the rats were subjected to an isolated working heart preparation: 30 min ischemia followed by 2 h of reperfusion with continuous left ventricular function monitoring. At the end, the hearts were subjected to either measurement of infarct size or cardiomyocyte apoptosis. Some hearts (from different sets of ex...

Cardioprotective properties of raw and cooked eggplant (Solanum melongena L)

Abstract: Although eggplants are known to be part of a healthy diet, the effects of this fruit on cardioprotection are not known. The present study examined the role of raw and grilled eggplants on cardioprotection using an isolated perfusion heart model. The animals were fed freeze-dried products of either raw or grilled eggplants for 30 days. After 30 days, isolated working hearts were subjected to 30 min ischemia followed by 2 h of reperfusion. Left ventricular function was monitored, and myocardial infarct size and cardiomyocyte apoptosis were assessed. To determine the antioxidant function of eggplants, their DPPH scavenging ability were determined, and polyphenolic components, especially nasunin content, were determined. The chemical composition of raw and grilled eggplants were determined in order to examine whether grilling was associated with major changes in their composition. The results of this study demonstrated eggplants as containing potent cardioprotective compounds judging by their ability to increase left ventricular function, and reduce myocardial infarct size and cardiomyocyte apoptosis. However, there was no difference in cardioprotective ability between the raw and grilled products. The antioxidant vitamins, including vitamin A, vitamin C and β-carotene, were lower and some of the polyphenolic components, especially nasunin content, were higher in grilled eggplants, but they were unable to demonstrate better cardioprotective properties compared to the raw fruit.

Attenuation of Ischemia/Reperfusion Injury in Rats by the Anti-inflammatory Action of Resveratrol

Abstract: Resveratrol (trans-3,4',5-trihydroxystilbene, CAS 501–36–0), a natural antioxidant and polyphenol found in grapes and wine, has been found to pharmacologically precondition the heart in nitric oxide (NO)-dependent manner. In the vascular system, NO functions as an endogenous inhibitor of leukocyte chemotaxis, adherence, and activation. The present study was designed to determine if resveratrol, through NO, can block the proadhesive molecules generated in the ischemic reperfused myocardium. Isolated hearts were prepared from properly anesthetized rats, and mounted on a Langendorff apparatus. The hearts were randomly assigned to one of the three groups: (i) control, (ii) resveratrol, and (iii) resveratrol + NG-nitro-L-arginine ethyl ester (L-NAME). The hearts were perfused in the absence (n = 6) or presence of 10 µmol/L resveratrol (n=6) or resveratrol + L-NAME (n = 6) for 15 min. All the hearts were then subjected to 30 min ischemia followed by 2 h of reperfusion. Ventricular function was monitored, infarct size and apoptotic cell death measured, and the proadhesive molecules and malonaldehyde formation determined in the perfusate. Resveratrol significantly improved postischemic ventricular function and reduced myocardial infarct size compared to the non-treated control group. The amount of proadhesive molecules including soluble intracellular adhesion molecule-1 (sICAM-1), endothelial leukocyte adhesion molecule-1 (sE-Selectin) and vascular cell adhesion molecule-1 (sVCAM-1) were each significantly decreased during reperfusion in the resveratrol group. L-NAME, a NO blocker, completely abolished such beneficial effects of resveratrol. The results support an anti-inflammatory action of resveratrol through a NO-dependent mechanism.

MicroRNA signatures of resveratrol in the ischemic heart

Abstract: Until the middle of the last decade, few people had heard of microRNAs (miRNAs), 21- to 23-nucleotide conserved RNAs. MicroRNAs represent a new paradigm because they regulate most physiological processes and thus have immense potential for medical advancement. Resveratrol, a red wine-derived polyphenolic compound, has been shown to have significant effects in various disease models, such as cardioprotection in ischemic heart, diabetes, and chemoprevention of cancers. The targets of resveratrol include various pathways and molecules, such as sirtuins, FOXOs, and autophagy. The successful application of resveratrol lies in understanding its mechanisms of action through direct and indirect interactions with pathways, including miRNAs. For example, a unique miRNA footprint is present in the heart treated with resveratrol. Targets of those miRNAs have potential implications for physiological and pathophysiological processes in health and disease.

Erratum to: Resveratrol and red wine, healthy heart and longevity

Abstract: Resveratrol, a polyphenol phytoalexin, present in red wine and grapes possesses diverse biochemical and physiological properties, including estrogenic, antiplatelet, and anti-inflammatory properties as well as a wide range of health benefits ranging from chemoprevention to cardioprotection. Recently, several studies described resveratrol as an anti-aging compound. This review focuses on the anti-aging aspects of resveratrol, the possible mechanisms of action, and emerging controversy on its life-prolonging ability. It appears that resveratrol can induce the expression of several longevity genes including Sirt1, Sirt3, Sirt4, FoxO1, Foxo3a and PBEF and prevent aging-related decline in cardiovascular function including cholesterol level and inflammatory response, but it is unable to affect actual survival or life span of mice.

Reduction of blood cholesterol and ischemic injury in the hypercholesteromic rabbits with modified resveratrol, logevinex

Abstract: The present study examined the efficacy of using longevinex, a commercially available resveratrol formulation, to lower blood cholesterol in hypercholesteromic rabbits. New Zealand white rabbits were randomly divided into two groups (n = 6 per group), one group was given high cholesterol diet for 3 months while the other group fed regular diet served as control. The high cholesterol diet fed group was further subdivided into two groups (n = 6 per group), one group was given longevinex resveratrol while the other group given vehicle only served as control. Longevinex was given by gavaging up to a period of 6 months. Longevinex-treated rabbits exhibited lowering of plasma cholesterol level. Inhibition of arterial plaque formation was noticed even after 1 month. Longevinex-treated hearts demonstrated improved ventricular recovery when isolated working hearts were subjected to 30 min of ischemia followed by 2 h of reperfusion. Aortic flow and developed pressure during post-ischemic reperfusion period were significantly higher for the longevinex-treated hearts compared to those in control group of hearts. Myocardial infarct size was also lower in the treated group compared to that for the untreated group. These results indicate cholesterol-lowering ability of longevinex, which appears to reflect in its ability to protect the hypercholesteromic hearts from ischemic reperfusion injury.

Resveratrol and health

Abstract: This volume examines the phytoalexin resveratrol and the ongoing studies about its effects on lifespan and health. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phytoalexin produced naturally by several plants when under attack by pathogens such as bacteria or fungi, significantly extends the lifespan of the yeast Saccharomyces cerevisiae, Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Resveratrol is currently a topic of numerous animal and human studies into its effects. The effects of resveratrol on the lifespan of many model organisms remain controversial. Anti-cancer, anti-inflammatory, blood-sugar-lowering, and other beneficial cardiovascular effects of resveratrol have been reported in experiments with mouse and rat model systems. However, most of these results have yet to be replicated in humans. Resveratrol is found in the skin of red grapes and is a constituent of red wine. Resveratrol has also been produced by chemical synthesis or by biotechnological synthesis and is sold as a nutritional supplement derived primarily from Japanese knotweed. NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please click here. ACADEMY MEMBERS: Please contact the New York Academy of Sciences directly to place your order (www.nyas.org). Members of the New York Academy of Science receive full-text access to the Annals online and discounts on print volumes. Please visit http://www.nyas.org/MemberCenter/Join.aspx for more information about becoming a member.

Tocotrienols and its role in cardiovascular health--a lead for drug design.

Abstract: The worldwide cardiovascular disease (CVD) burden has resulted in an intense interest in pharmaceutical approaches to combat this multifactorial disease. Vitamins are high-flying among natural or endogenous compounds, considered to be beneficial to human health and have become attractive targets for research. Of all the vitamins, tocopherols and tocotrienols, parent congeners in the vitamin E family, are found to be effective in decreasing mortality due to CVD. As understanding of the antioxidant effect of this vitamin evolved, tocotrienols gained eminence in recent years and researchers begun to further study the biological effects of it. Tocotrienols have several cardioprotective effects; including antagonizing the oxidation of low density lipoproteins, anti atherosclerotic, inhibiting platelet aggregation and monocyte adhesion, preventing smooth muscle proliferation and various other cardiovascular disorders. Recent studies have also revealed the molecular targets of the tocotrienols and their roles in cancer, bone resorption, diabetes and neurological diseases at both preclinical and clinical levels. The multitargeted role of tocotrienols in most degenerative diseases proves it to be an ideal candidate as a nutraceutical/pharmaceutical agent for useful exploitation.

Erratum: Reduction of blood cholesterol and ischemic injury in the hypercholesteromic rabbits with modified resveratrol, longevinex (Mol Cell Biochem DOI: 10.1007/s11010-010-0615-2)

Abstract: In the original article several inaccuracies have been noticed after the article has been published online. The title should have read: Reduction of blood cholesterol and ischemic injury in the hypercholesteromic rabbits with modified resveratrol, longevinex The name of first author has not been spelled correctly and should read Bela Juhasz. The acknowledgement should have mentioned that the paper was partially supported by OTKA 78223. Everything else in the paper remains correct.

Stem Cell, MicroRNA and Redox Cycling

Abstract: Mobilization and homing of the hematopoietic stem cells appear to be regulated by mechanism involving redox cycling. Stem cells are localized inside bone marrow in a strictly hypoxic environment and must move to the injury site that is subjected to oxidative environment. Cytokines and adhesion molecules control stem cell mobilization through a redox-regulated process. The major hitch in stem cell therapy includes the life of the stem cells after the stem cell therapy; most cells do not survive beyond 24–72 h. Sudden exposure of the stem cells from the hypoxic melieu into the oxidative environment likely causes severe injury to the cells. FoxO-SirT network appears to be intimately involved in redox-regulated stem cell homeostasis, while their differentiation process is regulated by redox factor protein-1, Ref-1. Lack of oxygen [hypoxia], specifically controlled hypoxia can stimulate the growth of the stem cells in their niche, and HIF-1α plays a significant role in their maintenance and homing mechanism. Recently, resveratrol, a polyphenolic phytoalexin, prolonged the survival of the stem cells as evidenced by active proliferation and differentiation of the cells even after 4 months of cell therapy. The enhancement of stem cell survival was shown to be due to the ability of resveratrol to maintain a reduced tissue environment by over-expressing Nrf2 and Ref-1 in rat heart up to 6 months resulting in an enhancement of the regeneration of the adult cardiac stem cells as evidenced by increased cell survival and differentiation leading to improved cardiac function. Expression of stromal cell-derived factor (SDF) and myosin conclusively demonstrated homing of stem cells in the infracted myocardium, its regeneration leading to improvement of cardiac function.

MicroRNA signatures of stem cells

Abstract: The unique properties of embryonic stem (ES) cells to self-renew indefinitely or to differentiate to any cell type (pluripotency) warrants their clinical application in regenerative medicine. MicroRNAs are crucial for post-transcriptional gene regulation and, thus, remain an essential element of the regulation of ES cells. The present review discusses the essential elements of microRNAs that regulate the life and death of ES cells.