Publications by authors named "Dipak K Das"

155 Publications

Erratum to "GATA-4 regulation of myocardial survival in the preconditioned heart" [J. Mol. Cell. Cardiol. 37(6) (2004 Dec) 1195-1203].

J Mol Cell Cardiol 2016 12 17;101:25. Epub 2016 Nov 17.

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yjmcc.2016.10.008DOI Listing
December 2016

Antiaging properties of a grape-derived antioxidant are regulated by mitochondrial balance of fusion and fission leading to mitophagy triggered by a signaling network of Sirt1-Sirt3-Foxo3-PINK1-PARKIN.

Oxid Med Cell Longev 2014 12;2014:345105. Epub 2014 Jan 12.

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT, USA ; Center for Medicinal Food and Applied Nutrition, Jadavpur University, Jadavpur, Kolkata, India.

It was proposed that resveratrol, a polyphenolic antioxidant and a calorie restriction mimetic could promote longevity but subsequent studies could not prove this. The original proposal was based on the fact that a grape-derived antioxidant could activate the antiaging gene Sirt1. Most studies agree that indeed grape activates Sirt1, but a question remains whether Sirt1 is the cause or consequence of resveratrol treatment. Subsequently, mitochondrial Sirt3 was found to be activated. The present study on ischemic reperfusion (I/R) in rat hearts demonstrates that Foxo3a is activated subsequent to Sirt3 activation, which then activates PINK1. PINK1 potentiates activation of PARKIN leading to the activation of mitochondrial fission and mitophagy. Confocal microscopy conclusively shows the coexistence of Sirt3 with Foxo3a and Foxo3a with PINK1 and PARKIN. Mitophagy was demonstrated both by confocal microscopy and transmission electron microscopy. Western blot analyses data are consistent with the results of confocal microscopy. It appears that the grape-derived antioxidant modifies the intracellular environment by changing the oxidizing milieu into a reducing milieu and upregulating intracellular glutathione, potentiates a signal transduction cascade consisting of Sirt1/Sirt3-Foxo3a-PINK1-PARKIN-mitochondrial fusion fission-mitophagy that leads to cardioprotection, and paves the way to an anti-aging environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/345105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942197PMC
November 2014

Controlling the femtosecond laser-driven transformation of dicyclopentadiene into cyclopentadiene.

Chem Phys Lett 2013 Feb;558:1-7

Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India.

Dynamics of the chemical transformation of dicyclopentadiene into cyclopentadiene in a supersonic molecular beam is elucidated using femtosecond time-resolved degenerate pump-probe mass spectrometry. Control of this ultrafast chemical reaction is achieved by using linearly chirped frequency modulated pulses. We show that negatively chirped femtosecond laser pulses enhance the cyclopentadiene photo-product yield by an order of magnitude as compared to that of the unmodulated or the positively chirped pulses. This demonstrates that the phase structure of femtosecond laser pulse plays an important role in determining the outcome of a chemical reaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cplett.2012.10.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3790071PMC
February 2013

Dynamic action of carotenoids in cardioprotection and maintenance of cardiac health.

Molecules 2012 Apr 23;17(4):4755-69. Epub 2012 Apr 23.

Department of Biotechnology, School of Life Sciences, Pondicherry University, Puducherry-605014, India.

Oxidative stress has been considered universally and undeniably implicated in the pathogenesis of all major diseases, including those of the cardiovascular system. Oxidative stress activate transcriptional messengers, such as nuclear factor-κB, tangibly contributing to endothelial dysfunction, the initiation and progression of atherosclerosis, irreversible damage after ischemic reperfusion, and even arrhythmia, such as atrial fibrillation. Evidence is rapidly accumulating to support the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as intracellular signaling molecules. Despite this connection between oxidative stress and cardiovascular disease (CVD), there are currently no recognized therapeutic interventions to address this important unmet need. Antioxidants that provide a broad, "upstream" approach via ROS/RNS quenching or free radical chain breaking seem an appropriate therapeutic option based on epidemiologic, dietary, and in vivo animal model data. Short-term dietary intervention trials suggest that diets rich in fruit and vegetable intake lead to improvements in coronary risk factors and reduce cardiovascular mortality. Carotenoids are such abundant, plant-derived, fat-soluble pigments that functions as antioxidants. They are stored in the liver or adipose tissue, and are lipid soluble by becoming incorporated into plasma lipoprotein particles during transport. For these reasons, carotenoids may represent one plausible mechanism by which fruits and vegetables reduce the risk of chronic diseases as cardiovascular disease (CVD). This review paper outlines the role of carotenoids in maintaining cardiac health and cardioprotection mediated by several mechanisms including redox signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules17044755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269032PMC
April 2012

Health benefits of wine and alcohol from neuroprotection to heart health.

Front Biosci (Elite Ed) 2012 Jan 1;4:1505-12. Epub 2012 Jan 1.

Herbal and Indian Medicine Research Laboratory, Sri Ramachandra University, Chennai-600116, India.

Controversy is common during efforts to define the role of nutrition in health, but few modern reflections of such controversy are as vivid as the debate over wine. There exists no query that chronic alcohol abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or never drinkers, light/moderate alcohol/wine consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer's disease (AD) Neurodegenerative diseases such as AD and Parkinson's (PD) diseases are defined by a progressive neuronal dysfunction and an ensuing behavioral dysfunction. Epidemiologic studies from numerous disparate populations reveal that individuals with the habit of daily moderate wine consumption enjoy significant reductions in all-cause and particularly cardiovascular and neurodegenerative mortality when compared with individuals who abstain or who drink alcohol in excess. Apart from the alcohol present in the wine, other trace compounds and polyphenolic compounds such as resveratrol naturally present in wine and grapes also exert neuroprotective and cardioprotective activities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2741/476DOI Listing
January 2012

Modified resveratrol Longevinex improves endothelial function in adults with metabolic syndrome receiving standard treatment.

Nutr Res 2011 Nov;31(11):842-7

Second Department of Internal Medicine, Kansai Medical University, Moriguchi 570-850, Japan.

Resveratrol is known to improve endothelial function in animals, but little is known about its effect on human subjects. Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors underlying endothelial dysfunction. We hypothesized that the modified resveratrol, Longevinex, improves endothelial function in patients with MetS. Thirty-four patients who had been treated for MetS and lifestyle-related disease were randomly assigned to group A, in which Longevinex was administered for 3 months and then discontinued for 3 months, whereas in the time-matched group B, Longevinex was administered between 3 and 6 months. These 2 groups of patients received similar drugs at baseline for diabetes mellitus, dyslipidemia, or hypertension. Flow-mediated dilatation significantly increased during the administration of Longevinex but decreased to baseline 3 months after the discontinuation of Longevinex in the group A patients. Conversely, in the group B patients, flow-mediated dilatation remained unchanged for the first 3 months without Longevinex but was significantly increased 3 months after the treatment with Longevinex. Longevinex did not significantly affect blood pressure, insulin resistance, the lipid profile or inflammatory markers during 6-month follow-up. These results demonstrate that Longevinex specifically improves endothelial function in subjects with MetS who were receiving standard therapy for lifestyle-related disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nutres.2011.09.028DOI Listing
November 2011

MicroRNA signatures of stem cells.

Exp Clin Cardiol 2011 ;16(3):e13-6

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut;

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209547PMC
November 2011

Modulation of microRNA 20b with resveratrol and longevinex is linked with their potent anti-angiogenic action in the ischaemic myocardium and synergestic effects of resveratrol and γ-tocotrienol.

J Cell Mol Med 2012 Oct;16(10):2504-17

Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.

Resveratrol, a constituent of red wine, and γ-tocotrienol, a constituent of palm oil are important for cardioprotection. Although microRNAs are known regulators for genes involved in cardiac remodelling, the regulatory pathway involving microRNA has not been studied so far. We explored the cardioprotection by resveratrol, longevinex and γ-tocotrienol in ischaemia/reperfusion(I/R) model of rat and determined miRNA profile from isolated RNA. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Resveratrol and γ-tocotrienol, either alone or in combination, modulated the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 75 miRNAs, some of them, such as miR-21 and miR-20b (anti-angiogenic) were previously implicated in cardiac remodelling. The target genes for the highest differentially expressed miRNA include genes of various molecular functions such as TGFβ1-Smad3 signalling pathway, inflammation and their transcription factors, which may play key role in reducing I/R injury. Administration of antagomiR-20 attenuated I/R induced vascular endothelial growth factor and HIF1α level. All the interventions treated for 3 weeks lead to significant cardioprotection against ischaemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or γ-tocotrienol. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R rat. Interestingly, resveratrol and γ-tocotrienol resulted in synergestic action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1582-4934.2011.01480.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823443PMC
October 2012

Oxygen Sensing, Cardiac Ischemia, HIF-1α and Some Emerging Concepts.

Curr Cardiol Rev 2010 Nov;6(4):265-73

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut, CT 06030- 1110, USA.

Oxygen plays a critical role in the perpetuation and propagation of almost all forms of life. The primary site of cellular oxygen consumption is the mitochondrial electron transport chain and in addition, oxygen is also used as a substrate for various enzymes involved in cellular homeostasis. Although our knowledge of the biochemistry and physiology of oxygen transport is century old, recent development of sophisticated tools of biophysical chemistry revealed that tissue oxygenation and oxygen sensing is a highly evolved process, especially in mammals. Perturbation of normal oxygen supply is associated with diseases like tumorigenesis, myocardial infarction and stroke. Available information suggests that when tissue oxygen supply is limited, mitochondria emanate signals involving reactive oxygen species generation which in turn stabilizes oxygen sensing transcription factor HIF-1. Upon stabilization, HIF-1 elicits necessary genetic response to cope with the diminished oxygen level. In view of such critical role of HIF-1 in cellular oxygen sensing, recently there has been a heightened interest in understanding the biology of HIF-1 in the context of cardiovascular system. The following review describes some of the recent advances in this regard.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/157340310793566136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083807PMC
November 2010

Tocotrienols confer resistance to ischemia in hypercholesterolemic hearts: insight with genomics.

Mol Cell Biochem 2012 Jan 15;360(1-2):35-45. Epub 2011 Sep 15.

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA.

Most clinical trials with vitamin E could not lower cholesterol and thus, have been deemed unsuccessful. Recently, tocotrienols, isomers of vitamin E have been found to lower LDL levels. To explore if tocotrienols could be the drug target for vitamin E, rabbits were kept on cholesterol diet for 60 days supplemented with tocotrienol-α, tocotrienol-δ, and tocotrienol-γ for the last 30 days. The serum cholesterol levels (in mmol/l) were 24.4 (tocotrienol-α), 34.9 (tocotrienol-δ), 19.8 (tocotrienol-γ) vs. 39.7 (control). Left ventricular function including aortic flow and developed pressure exhibited significantly improved recovery with tocotrienol-γ and -α, but not with tocotrienol-δ. The myocardial infarct size showed a similar pattern: 33% (tocotrienol-α), 23% (tocotrienol-γ), and 47% (tocotrienol-δ). To examine the molecular mechanisms of cardioprotective effects, gene expression profile was determined using Atlas 1.2/1.2II followed by determination of gene profiles using PedQuest 8.3 software. Based on genomic profiles, the following cholesterol-related proteins were examined: FABP, TGF-β (cholesterol suppresses TGF-β), ET-1 (increased by hypercholesterolemia), SPOT 14 (linked with hypercholesterolemia), and matrix metalloproteinase (MMP) 2 and MMP9 (cholesterol regulates MMP2 and MMP9 expression) in the heart. Consistent with the cardioprotective effects of tocotrienol-α and -γ, these two isomers reduced ET-1, decreased MMP2 and MM9, increased TGF-β and reduced SPOT 14, while tocotrienol-δ had no effects. The results of the present study demonstrate that the two isomers of tocotrienols, α and γ, render the hypercholesterolemic hearts resistant to ischemic reperfusion injury by lowering several hypercholesterolemic proteins including MMP2, MMP9, ET-1, and SPOT 14 and upregulating TGF-β.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-011-1041-9DOI Listing
January 2012

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

Food Funct 2011 Jul 10;2(7):395-9. Epub 2011 Jun 10.

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c1fo10048cDOI Listing
July 2011

Towards Using Molecular States as Qubits.

AIP Conf Proc 2011 Sep;1384(1):251-253

Department of Chemistry, Indian Institute of Technology Kanpur Kanpur - 208016, INDIA.

Molecular systems are presented as possible qubit systems by exploring non-resonant molecular fragmentation of n-propyl benzene with femtosecond laser pulses as a model case. We show that such laser fragmentation process is dependent on the phase and polarization characteristics of the laser. The effect of the chirp and polarization of the femtosecond pulse when applied simultaneously is mutually independent of each other, which makes chirp and polarization as useful 'logic' implementing parameters for such molecular qubits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/1.3635869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3695453PMC
September 2011

Retraction Notice: Tocotrienols and its Role in Cardiovascular Health- a Lead for Drug Design

Curr Pharm Des 2011 ;17(21):2170-5

Department of Biotechnology, School of Life Sciences, Pondicherry University, Puducherry-605014, India.

The article has been retracted by the Editorial office of the journal Current Pharmaceutical Design, due to some inconsistencies in the article [1]. The article appeared to be copied verbatim from published papers. Upon checking these facts, we have established that considerable portions of this review are made up of text copied verbatim from other published material. The Publisher has retracted this article in accordance with good ethical practices.

Reference: [1] Vasanthi HR, Parameswari RP and Das DK. Tocotrienols and its Role in Cardiovascular Health- a Lead for Drug Design. Curr Pharm Des 2011; 17(21): 2170-5. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Retraction can be found at https://benthamscience.com/editorial-policies-main.php.

Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/138161211796957508DOI Listing
May 2012

Caveolin induces cardioprotection through epigenetic regulation.

J Cell Mol Med 2012 Apr;16(4):888-95

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06-030-1110, USA.

Lipid rafts represent a sub-compartment of the plasma membrane that co-ordinate and regulate varieties of signalling processes, whereas caveolins are the integral membrane protein of the lipid raft. Recent evidence demonstrated the pivotal role of caveolins in cardioprotection against ischaemic injury, although their mechanism of action is not clear. However, new understanding of epigenetic modification during ischaemia reperfusion suggests additional targeted approaches that have not been explored before. To study the role of caveolin on epigenetic regulation, isolated mouse heart was prepared from wild-type (WT) and caveolin-1 knockout (Cav-1 KO) mouse and preconditioned them with four cyclic episodes of ischaemia/reperfusion followed by 30 min. global ischaemia and 120 min. reperfusion. We found that Cav-1 KO mouse abolished the acetylation of histone (H3 and H4) and increased the methylation of histone in the preconditioned heart. The increased histone methylation was significantly correlated with an increased level of histone methyltranferase G9a protein and increased the level of histone decaetylase (HDAC) activity. Cav-1 KO mouse also decreased the translocation of forkhead transcription factor (FOXO3a) to the nucleus and reduced the induction of the expression of SIRT-1 in the preconditioned heart. Cardioprotective property of Cav-1 was further confirmed by reduced ventricular function, increased cardiomyocyte apoptosis, increased expression of junas kinase (JNK) and Bax and decreased expression of phospho-adenosine monophosphate-activated protein kinase (AMPK), phospho-AKT and B cell lymphoma-2 (Bcl-2) in Cav-1 KO preconditioned heart. The results clearly indicate that Cav-1 induces cardioprotection through epigenetic regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1582-4934.2011.01372.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822857PMC
April 2012

What is new for an old molecule? Systematic review and recommendations on the use of resveratrol.

PLoS One 2011 16;6(6):e19881. Epub 2011 Jun 16.

Department of Science, System and Models, Roskilde University, Roskilde, Denmark.

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 Helsingør, 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0019881PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3116821PMC
November 2011

Caveolae, caveolin, and cavins: potential targets for the treatment of cardiac disease.

Ann Med 2012 Sep 9;44(6):530-41. Epub 2011 Jun 9.

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA.

Caveolae are omega-shaped membrane invaginations present in essentially all cell types of the cardiovascular system, including endothelial cells, smooth muscle cells, macrophages, cardiac myocytes, and fibroblasts. Numerous functions have been ascribed to this omega-shaped structure. Caveolae are enriched with different signaling molecules and ion channel regulatory proteins and function both in protein trafficking and signal transduction in these cell types. Caveolins are the structural proteins that are necessary for the formation of caveola membrane domains. Mechanistically, caveolins interact with a variety of downstream signaling molecules, as, for example, Src-family tyrosine kinase, p42/44 mitogen-activated protein (MAP) kinase, and endothelial nitric oxide synthase (eNOS) and hold the signal transducers in the inactive condition until activated with proper stimulus. Caveolae are gradually acquiring increasing attention as cellular organelles contributing to the pathogenesis of several structural and functional processes including cardiac hypertrophy, atherosclerosis, and heart failure. At present, very little is known about the role of caveolae in cardiac function and dysfunction, although recent studies with caveolin knock-out mouse have shown that caveolae and caveolins play a pivotal role in various human pathobiological conditions. This review will discuss the possible role and mechanism of action of caveolae and caveolins in different cardiac diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/07853890.2011.577445DOI Listing
September 2012

Multifaceted role of tocotrienols in cardioprotection supports their structure: function relation.

Genes Nutr 2012 Jan 21;7(1):19-28. Epub 2011 May 21.

Department of Biotechnology, School of Life Sciences, Pondicherry University, Puducherry, Puducherry, India.

Tocotrienols are a class of vitamin E which modulates several mechanisms associated with cardioprotection, anti-cancer, anti-diabetic, and neuroprotection. Unlike other Vitamin E-like compounds, tocotrienols possess inimitable properties. Quite a lot of studies have determined the cardioprotective abilities of tocotrienols and have been shown to possess novel hypocholesterolemic effects together with an ability to reduce the atherogenic apolipoprotein and lipoprotein plasma levels. In addition, tocotrienol has been suggested to have an antioxidant, anti-thrombotic, and anti-tumor effect indicating that tocotrienol may serve as an effective agent in the prevention and/or treatment of cardiovascular disease and cancer. The bioactivity exhibited is due to the structural characteristics of tocotrienols. Rich sources of tocotrienols which include rice bran, palm oil, and other edible oils exhibit protective effect against cardiovascular disorders. The conclusions drawn from the early literature that vitamin E group of compounds provides an inevitable role in cardioprotection is sustained in many more recent studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12263-011-0227-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250529PMC
January 2012

Erratum to: resveratrol and red wine, healthy heart and longevity.

Heart Fail Rev 2011 Jul;16(4):425-35

Cardiovacular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10741-011-9234-6DOI Listing
July 2011

Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells.

J Cell Mol Med 2012 Jan;16(1):174-84

The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.

The major problem in stem cell therapy includes viability and engraftment efficacy of stem cells after transplantation. Indeed, the vast majority of host-transfused cells do not survive beyond 24-72 hrs. To increase the survival and engraftment of implanted cardiac stem cells in the host, we developed a technique of treating these cells with resveratrol, and tested it in a rat model of left anterior descending (LAD) occlusion. Multi-potent clonogenic cardiac stem cells isolated from rat heart and stably transfected with EGFP were pre-treated with 2.5 μM resveratrol for 60 min. Rats were anaesthetized, hearts opened and the LAD occluded to induce heart attack. One week later, the cardiac reduced environment was confirmed in resveratrol treated rat hearts by the enhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). M-mode echocardiography after stem cell therapy, showed improvement in cardiac function (left ventricular ejection fraction, fractional shortening and cardiac output) in both, the treated and control group after 7 days, but only resveratrol-modified stem cell group revealed improvement in cardiac function at the end of 1, 2 and 4 months time. The improvement of cardiac function was accompanied by enhanced stem cell survival and engraftment as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the expression of EGFP up to 4 months after LAD occlusion in the resveratrol-treated stem cell group. Expression of stromal cell-derived factor and myosin conclusively demonstrated homing of stem cells in the infarcted myocardium, its regeneration leading to improvement of cardiac function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1582-4934.2011.01281.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823103PMC
January 2012

Hormetic response of resveratrol against cardioprotection.

Exp Clin Cardiol 2010 ;15(4):e134-8

Cardiovascular Research Center, University of Connecticut School of Medicine, Connecticut, USA;

Resveratrol, a grape- and red wine-derived polyphenolic phytoalexin, shows diverse health benefits including cardioprotection. Recent studies implicate that resveratrol displays hormetic action, protecting the cells at a lower dose while killing them at relatively higher doses. Because such hormetic behaviour may have a significant impact on epidemiological and clinical studies, the present study sought to determine dose-response curves for resveratrol action. In parallel, another resveratrol formulation was tested, namely, Longevinex (Resveratrol Partners LLC, USA). A group of rats were force-fed three different doses of resveratrol or Longevinex (2.5 mg/kg, 25 mg/kg and 100 mg/kg) for up to 30 days, while the control group was only given placebo. The results showed hormesis for pure resveratrol, which was cardioprotective at lower doses and detrimental for higher doses, but surprisingly Longevinex did not display any hormetic action. In the concentration range studied, Longevinex remained cardioprotective even at 100 mg/100 g body weight - a dose that killed 100% of the hearts when tested with pure resveratrol. To further test whether Longevinex doses are beneficial for other animal species, Longevinex was gavaged to a group of rabbits for six months, and showed exactly the same degree of cardioprotection. Cardioprotection was examined in isolated working hearts subjected to 30 min of ischemia followed by 2 h of reperfusion; left ventricular performance and infarct size was also examined. It appears that Longevinex does not show any hormetic action, while resveratrol clearly does.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016073PMC
July 2011

MicroRNA signatures of resveratrol in the ischemic heart.

Ann N Y Acad Sci 2011 Jan;1215:109-16

Laboratory of Physiologic Studies, NIAAA, National Institute of Health, Bethesda, Maryland, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1749-6632.2010.05866.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3059201PMC
January 2011

Resveratrol in cardiovascular health and disease.

Ann N Y Acad Sci 2011 Jan;1215:22-33

Department of Biochemistry and Molecular Biology, University of Debrecen, Hungary.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1749-6632.2010.05843.xDOI Listing
January 2011

Restoration of altered microRNA expression in the ischemic heart with resveratrol.

PLoS One 2010 Dec 23;5(12):e15705. Epub 2010 Dec 23.

Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, Maryland, United States of America.

Background: Resveratrol, a constituent of red wine, is important for cardioprotection. MicroRNAs are known regulators for genes involved in resveratrol-mediated cardiac remodeling and the regulatory pathway involving microRNA has not been studied so far.

Methods: We explored the cardioprotection by resveratrol in ischemia/reperfusion model of rat and determined cardiac functions. miRNA profile was determined from isolated RNA using quantitative Real-time PCR based array. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches.

Results: Cardioprotection by resveratrol and its derivative in ischemia/reperfusion [I/R] rat model was examined with miRNA expression profile. Unique expression pattern were found for each sample, particularly with resveratrol [pure compound] and longevinex [commercial resveratrol formulation] pretreated hearts. Longevinex and resveratrol pretreatment modulates the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 25 miRNAs, some of them, such as miR-21 were previously implicated in cardiac remodeling. The target genes for the differentially expressed miRNA include genes of various molecular function such as metal ion binding, sodium-potassium ion, transcription factors, which may play key role in reducing I/R injury.

Conclusion: Rats pretreated with resveratrol for 3 weeks leads to significant cardioprotection against ischemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or longevinex. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0015705PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009730PMC
December 2010

Dose-dependency of resveratrol in providing health benefits.

Dose Response 2010 Mar 18;8(4):478-500. Epub 2010 Mar 18.

Cardiovascular Research Center, University of Connecticut Health Center, School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-1110, USA.

This review describes the dose-dependent health benefits of resveratrol, a polyphenolic antioxidant that is found in a variety of foods, especially grape skin and red wine. Resveratrol provides diverse health benefits including cardioprotection, inhibition of low-density lipoprotein, activation of nitric oxide (NO) production, hindering of platelet aggregation [32] A.A.E. Bertelli, D.E. Giovannini, R.L. Caterina, W. Bernini, M. Migliori and M. Fregoni et al., Antiplatelet activity of cis-resveratrol, Drugs Exp Clin Res 22 (1996), pp. 61-63. View Record in Scopus | Cited By in Scopus (111) and promotion of anti-inflammatory effects. Studies have shown that at a lower dose, resveratrol acts as an anti-apoptotic agent, providing cardioprotection as evidenced by increased expression in cell survival proteins, improved postischemic ventricular recovery and reduction of myocardial infarct size and cardiomyocyte apoptosis and maintains a stable redox environment compared to control. At higher dose, resveratrol acts as a pro-apoptotic compound, inducing apoptosis in cancer cells by exerting a death signal. At higher doses, resveratrol depresses cardiac function, elevates levels of apoptotic protein expressions, results in an unstable redox environment, increases myocardial infarct size and number of apoptotic cells. At high dose, resveratrol not only hinders tumor growth but also inhibits the synthesis of RNA, DNA and protein, causes structural chromosome aberrations, chromatin breaks, chromatin exchanges, weak aneuploidy, higher S-phase arrest, blocks cell proliferation, decreases wound healing, endothelial cell growth by fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor, and angiogenesis in healthy tissue cells leading to cell death. Thus, at lower dose, resveratrol can be very useful in maintaining the human health whereas at higher dose, resveratrol has pro-apoptotic actions on healthy cells, but can kill tumor cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2203/dose-response.09-015.MukherjeeDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990065PMC
March 2010

Commentary on 'resveratrol commonly displays hormesis: occurrence and biomedical significance' by Calabrese et al.

Authors:
Dipak K Das

Hum Exp Toxicol 2010 Dec;29(12):1016-7

Cardiovascular Research Center, University of Connecticut, Farmington, CT 06030, USA.

Resveratrol, a grape skin and red wine-derived polyphenolic phytoalexin, exhibits hormetic action delivering numerous health benefits at lower doses while being detrimental at higher doses. Epidemiologic and clinical trials need to be based on the clear understanding of hormetic health benefits of resveratrol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0960327110383626DOI Listing
December 2010

Does autophagy take a front seat in lifespan extension?

J Cell Mol Med 2010 Nov;14(11):2543-51

Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.

This review focuses on the interrelationship between ageing and autophagy. There is a striking similarity between the signalling aspects of these two processes. Both ageing and autophagy involve several of the signalling components such as insulin/IGF-1, AMPK, Ras-cAMP-PKA, Sch9 and mTOR. Ageing and ageing-mediated defective autophagy involve accumulation of lipofuscin. Components of anti-ageing and autophagy include SirTs and FoxOs. Nutritional deprivation or calorie restriction as well as several nutriceuticals including resveratrol, spermidine, curcumin and piperine can enhance autophagy and increase lifespan. Such striking similarities indicate that lifespan is strongly dependent on autophagy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1582-4934.2010.01196.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373474PMC
November 2010

Natural products for the healthy heart.

Authors:
Dipak K Das

Curr Pharm Biotechnol 2010 Dec;11(8):792-3

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/138920110793262042DOI Listing
December 2010

Effects of Longevinex (modified resveratrol) on cardioprotection and its mechanisms of action.

Can J Physiol Pharmacol 2010 Nov;88(11):1017-25

Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1912, USA.

Although resveratrol has been proven to possess diverse health benefits, several recent reports have demonstrated conflicting results on some aspects of its effects, including its anti-aging properties. Considerable debate appears to exist on the dose and bioavailability of resveratrol, leading to the controversies on its effectiveness. To resolve the problem, we designed a study with a resveratrol formulation that contained resveratrol supplemented with 5% quercetin and 5% rice bran phytate (commercially known as Longevinex). These ingredients were micronized to increase the bioavailability. Sprague-Dawley rats were gavaged with either Longevinex or vehicle (5% quercetin plus 5% rice bran phytate), and rats were sacrificed after 1 or 3 months, when isolated working hearts were subjected to 30 min ischemia followed by 2 h of reperfusion. Longevinex-treated hearts, irrespective of the duration of treatments, revealed superior cardiac performance, reduced infarct size, and induction of survival signals as evidenced by increased Bcl2/Bax ratio and enhanced Akt phosphorylation. In contrast, LC3-II and Beclin were enhanced significantly after 3 months of Longevinex treatment, suggesting that autophagy occurred only after feeding Longevinex to rats for a prolonged period of time. Corroborating with the results of autophagy, Sirt1 and Sirt3 increased significantly only after 3 months of Longevinex treatment, suggesting that enhanced expression of Sirts correlated with induction of autophagy. In concert, Longevinex caused phosphorylation and nuclear translocation of FoxO1, FoxO3a, and FoxO4, indicating involvement of FoxOs with autophagy. Since Sirts and FoxOs are reliable markers of longevity, the results appear to suggest that Longevinex induces longevity after prolonged feeding via induction of autophagy, while it converts death signals into survival signals and provides cardioprotection within a relatively shorter period of time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/y10-082DOI Listing
November 2010