Current Pharmaceutical Biotechnology - Volume 11, Issue 8, 2010
Volume 11, Issue 8, 2010
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Editorial [Hot Topic: Natural Products for the Healthy Heart (Guest Editor : Dipak K. Das)]
By Dipak K. DasCardiovascular diseases remain the primary cause for the morbidity and mortality in the developed countries including United States of America. Maintaining a healthy heart is particularly important for those with a family history of coronary heart disease including hypertension, heart attack and atherosclerosis. Regular consumption of healthy food and maintaining a healthy life style certainly help maintaining a disease free life. Certain mineral-rich foods including those high in potassium, calcium and magnesium can control blood pressure. Low-fat milks are rich sources of calcium while magnesium and potassium can be found in green vegetables and fish oil. Among the fatty foods, limiting saturated, polyunsaturated, monounsaturated and trans fat would help reducing cholesterol and coronary heart diseases. Major sources of saturated fat include beef, butter, cheese, whole milk and coconut and palm oils. In contrast, polyunsaturated fats like omega-3-fatty acids containing foods including fish oil, flax seed oil and canola oil may reduce the risk of heart attack. Some of the examples for maintaining healthy heart include garlic, olive oil, broccoli, capsicum, Coenzyme Q10, fax seed, Terminalia Arjuna, Ashwagandha, Cocoa and fish oil. The present review series are carefully selected to cover most of the varieties of heart heath foods that can be found in Nature. Kailash Prasad, M.D., Ph.D. in Saskatoon, Canada, an authority of flax seed oil, has written a review on the slowing the progression of atherosclerosis with flaxseed oil. He has shown that although flaxseed oil does not regress hypercholesterolemic atherosclerosis, it slows the progression of atherosclerosis. Slowing of the progression of atherosclerosis could be due to a decrease in oxidative stress because of the antioxidant activity of flax seed oil. Etsuo Niki, Ph.D., from Osaka, Japan has described the assessment of antioxidant capacity of natural products. Professor Niki is a renowned scientist in antioxidant research. He has described various methods for the assessment of antioxidant capacity of natural products. In this review, Dr. Niki has also described antioxidant defense network in the cardiovascular system and bioavailability of these antioxidants. Arpad Tosaki, Ph.D., D.Sc., Professor, Chairman and Dean of the Pharmaceutical Sciences at the University of Debrecen, Hungary, has reviewed how grape skin and red wine derived polyphenolic antioxidant resveratrol can exert multifunctional cardioprotective abilities. Resveratrol possesses multifunctional health benefitsv including cardioprotective ability, acticancer activity, antidiabetic property and anti-hypercholesteromic effects. He and his colleagues have described how resvratrol can control such a diverse health benefits. Belma Turan, Ph.D., Professor and Head of Biophysics in Ankara University, Turkey, has described fow antioxidant foods moderate cardiovascular complications due to diabetes. She has reviewed the properties of several anatioxidant foods that not only scavenge oxygen-derived free radicals, but also can function as PPAR agonist to combat diabetic complications. In addition, Dr. Turan has discussed studies identifying redox-sensitive cardiac proteins responsible for redox signaling in cardiovascular system. Cesar G Fraga, Ph.D., a professor in Biochemistry and Pharmacyat the University of Buenos Aires, Argentina and a Scientist at the Department of Nutrition, Univrsity of California at Davis has reviewed the role of dietary plant polyphenols in hyperyension He is an expert in antioxidant research and described current evidence linking consumption of these polyphenols linking with the reductionof high blood pressure. Consumption of cocoa and chocolate, grapes and wines, as well as black and green tea regulate nitric oxide bioavailability and blood pressure justifying the consumption of such polyphenol-rich foods to maintain blood pressure. Dipak K. Das, Ph.D., Sc.D., M.D (Hon), FAHA from the University of Connecticut School of Medicine, USA and Aldo Bertelli, M.D., Ph.D./Mario Falchi, Ph.D. from the University of Milan, Italy jointly wrote an original manuscript describing how calendula officinalis [marigold] can ameliorate myocardial injury due to ischemia and reperfusion. This flower can lower blood pressure, cholesterol and reduce the incidence of ischemic heart disease. The results of the present study cleary demonstrated that this flower extract reduced myocardial ischemic reperfusion injury by reducing inflammatory response in the heart. Subir Maulik, M.D., Ph.D., a professor of Pharmacology at the All India Institute of Medical Sciences has described ho Terminlia Arjuna made the transition from traditional to modern medicine in India. In traditional medicine stem bark of Terminalia Arjuna was used by the Ayurvedic Physicians in India for the treatment of various cardiovascular diseases, collectively referred to as hyritroga. In modern era, several clinical trials have proved this plant to be beneficial for the patients with stable angina, endothelial dysfunction, heart failure and ischemic mitral regurgitation. Tilman Grune, Ph.D. from the Institute of Biological Chemistry and Nutrition, University of Hohenhein, Stuttgart, Germany has described cardioprotective effects of curcumin and Ginkgo biloba. He and his colleagues describe an original study using two groups of SAMP8 mice fed a Western diet and Western diet plus curcumin or Ginkgo biloba extract. Analysis of various antioxidants and anflammatory mediators revieled that SAMR1 or SAMP8 nor curcumn/Ginkgo biloba affected the concentration of measured parameters suggesting that these strains are not suitable to study these parameters. Baolu Zhao, Ph.D. from the Institute of Biophysics, Chinese Academy of Sciences, Beijing, China, has reviewed potential benefits of using antioxidants to reduce myocardial ischemic reperfusion injury. He ad his coauthor has carefully described pros and cons of using these antioxidant compounds. Esuya Konishi, Ph.D., from the Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan, has discussed squalene as a novel food factor. Squalene was first identified in shark liver as a healing substance and now shown to be an effective functional food. This antioxidant substance possesses anticancer ability and can reduce plasma cholesterol. Lindsay Brown, Ph.D. from the University of Queensland Brisbane, Australia, has described how green tea can attenuate cardiovascular remodeling in high carbohydrate-fed rats. A group of scientists led by Professor Brown have shown how green tea could improve both cardiovascular symtoms and glucose intolerance simultaneously reducing oxidative stress in rats fed a high cabohydrate diet. The results clearly demonstrate that green tea reversed cardiovascular remodeling and metabolic changes seen in high-carbohydrate fed rats suggesting that green tea may be a useful complementary therapy in diet induced type 2 diabetes. Hannah R Vasanthi, Ph.D. and G.V.Rajamanickam, Ph.D. from the Center for Advance Research in Indian System of Medicine, Sastra University and Department of Biochemistry, Sri Ramachandra Medical College and Research Institute, Tamilnadu, India has contributed an original article describing that a flavonoid rich fraction of Dioscorea bulbifera (TAM) enhances mitochondrial enzymes and antioxidant status thereby protecting heart from isoproterenol-induced myocardial infarction. The results suggest the cardioprotective effect of yam in myocardial infarction was due to its ability to attenuate lipid peroxidation by scavenging free radicals and to modulate energy producing mitochondrial enzymes. Yi Zhun Zhu, Ph.D. Professor of the National University of Singapore, Singapore, has described the antiapoptotic effects of a novel compound from Herba leonuri Leonurine )SCM-198) through the inhibition of mitochondrial dysfuncti9on in H9c2 cells. In this original article, the authors showed that leonurine could protect H9c2 cells from H2O2-induced apoptosis via modulation of mitochondrial dysfunction associated with blocking the activation of JNK. Grant N. Pierce, Ph.D., a well-known nutritionist from the University of Manitoba, Winnipeg Manitoba along with Dr. Paramjit S Tappia, Ph.D. and Pallab K Ganguly M.D., from the Alfaisal Univrsity, Riyadh, Saudi Arabia, has shown how vanadate in a tea decoction couls restore cadiac function in streptozotocin-induced diabetic rats. The authors show that administration of black tea extract for a period of 8 weeks could prevent the defect in IP3/PLC signaling that occurs in diabetes and could restore normal cardiac contractile function. Finally, Joel de Leiris, Ph.D. and Franko Boucher, Ph.D. from thev University of Grenoble, France have described that moderate wine drinking can strengthen the cardioprotective effect of fish consumption. The review addresses the role of two of the specific components of the Mediterranean diet, omega 3 fatty acids and wine and establishes a link between moderate wine consumption and fatty acid profiles. It is my hope that this special issue on nutrition and healthy heart would help the readers to change the eating habits by consuming heart-healthy foods. It should be clear from the above review series that it is important to limit unhealthy fats such as saturated and trans fats and cholesterol-rich foods simultaneously choosing healthy fats from olive oil, fax seed oil or canola oil and eating fruits and vegetables and whole grain and fibre rich foods.
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Natural Products in Regression and Slowing of Progression of Atherosclerosis
More LessMany natural products, including vitamin E, garlic, purpurogallin, flaxseed and its components [secoisolariciresinol diglucoside (SDG) and flax lignan complex (FLC)] and resveratrol have been reported to suppress hypercholesterolemic atherosclerosis. It is known that all of the drugs that suppress the development of atherosclerosis do not regress and/or slow the progression of atherosclerosis. To be of potential benefit in patients with established atherosclerosis, a drug should produce regression and/or slow the progression of atherosclerosis. In this review, the effects of vitamin E, SDG and FLC in the regression and slowing of progression of hypercholesterolemic atherosclerosis and their mechanisms have been described. The effectiveness of vitamin E in patients with established coronary disease is very controversial. However, in experimental animal controlled studies, vitamin E does not regress or slow the progression of hypercholesterolemic atherosclerosis. The mechanisms of the ineffectiveness of vitamin E in regression and slowing of progression of atherosclerosis have been discussed. SDG is effective in slowing the progression of atherosclerosis and partially effective in regression of hypercholesterolemic atherosclerosis. These effects are associated with reduction in oxidative stress. FLC does not regress hypercholesterolemic atherosclerosis but slows the progression of hypercholesterolemic atherosclerosis. Slowing of progression is associated with reduction on oxidative stress. In conclusion, vitamin E does not regress or slow the progression of established atherosclerosis. SDG slows the progression and regresses established atherosclerosis. FLC does not regress but slows the progression of established atherosclerosis.
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Assessment of Antioxidant Capacity of Natural Products
By Etsuo NikiIt is now widely accepted that oxidative stress induced by reactive oxygen and nitrogen species is involved in the pathogenesis of various diseases such as atherosclerosis and cardiovascular disease and consequently the role of antioxidants in the prevention and treatment of diseases has received much attention of scientists, clinicians and general public. However, most of the large clinical intervention trials of antioxidants and meta-analysis of the data from these large studies do not show beneficial evidence with regard to cardiovascular outcomes. In order to understand the role of antioxidants, it is essential to elucidate the action and capacity of antioxidants. In this article, the assessment of antioxidant capacity is reviewed and the methods for assessment of natural antioxidant capacity are discussed.
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Resveratrol: A Multifunctional Cytoprotective Molecule
Authors: Bela Juhasz, Balazs Varga, Rudolf Gesztelyi, Adam Kemeny-Beke, Judit Zsuga and Arpad TosakiSeveral recent studies have shown the protective effects of resveratrol in various experimental conditions and pathological animal models. Clinical studies also indicate the beneficial effects of resveratrol in different human diseases. Resveratrol produces a cascade against of events from the initial death-provoking signal, DNA fragmentation, and cell death. Researchers recognized the beneficial effect of resveratrol, as an important component, of the overall injury that occurs in various disorders such as oxidative stress, myocardial injury, anticancer activity, antidiabetic activity, and antihypercholesterolemic effects. Many mechanisms have been proposed for the initiation of protective effects of resveratrol in various pathological events, and considerable evidence exists to indicate that many mediators are involved in the resveratrol- induced protection. The present review focuses on the history, and the beneficial effects and mechanisms of resveratrol in oxidative stress, myocardial injury, anticancer-, antidiabetic- and antihypercholesterolemic activities, and discusses those therapeutic tools, which warrant becoming clinically important. s
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Role of Antioxidants in Redox Regulation of Diabetic Cardiovascular Complications
By Belma TuranCardiovascular dysfunction is leading cause for the mortality of diabetic individuals, in part due to a specific cardiomyopathy, and due to altered endothelial dependent/independent vascular reactivity. Cardiovascular complications result from multiple parameters including glucotoxicity, lipotoxicity, fibrosis and mitochondrial uncoupling. Oxidative stress arises from an imbalance between the production of reactive oxygen and nitrogen species (ROS and RNS) and the capability of biological system to readily detoxify reactive intermediates. Several studies have reported beneficial effects of a therapy with antioxidant agents, including trace elements and other antioxidants, against the cardiovascular system dysfunction due to the diabetes. Antioxidants act through different mechanisms to prevent oxidant-induced cell damages acting either directly or indirectly. They can reduce the generation of ROS, scavenge ROS, or interfere with ROS-induced alterations. Modulating mitochondrial activity is an important possibility to control ROS production. Hence, the use of PPAR agonist to reduce fatty acid oxidation and of trace elements such as selenium as antioxidant and other antioxidants such as vitamins E and C, contribute to the prevention of diabetes-induced cardiovascular dysfunction. The paradigm that, inhibiting the overproduction of superoxides and peroxides would prevent cardiac dysfunction in diabetes has been difficult to verify using conventional antioxidants like vitamins E and C, that led to use of catalytic antioxidants such as SOD/CAT mimetics. Hence, well-tuned, balanced and responsive antioxidant defence systems are vital for proper prevention against diabetic damage. Myocardial cell death is observed in the hearts of diabetic patients and animal models; however, its importance in the development of diabetic cardiomyopathy is not completely understood. This review aims to summarize our present knowledge on various strategies to control oxidative stress and antagonize cardiovascular dysfunction during diabetes. In here, I consider aspects of redox signaling in the cardiovascular system, focusing on the molecular basis of redox sensing by proteins and the array of post-translational oxidative modifications that can occur. In addition, I discuss studies identify redox-sensitive cardiac proteins, as well as those assessing redox signalling in cardiovascular disease.
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Hypertension, Nitric Oxide, Oxidants, and Dietary Plant Polyphenols
Authors: Monica Galleano, Olga Pechanova and Cesar G. FragaFruits and vegetables are key foods whose high ingestion is associated with the improvement of numerous pathological conditions, including hypertension. Such health promoting actions have been increasingly ascribed to the antioxidant characteristics of different polyphenols in fruits and vegetables. Consequently, based on this assumption, many beverages and foods rich in polyphenols, grape, tea, cocoa, and soy products and many of their chemical constituents purified, are being studied both, as antioxidants and antihypertensive agents. This paper reviews the current evidence linking high polyphenol consumption with reductions in blood pressure. Basic chemical aspects of flavanols, flavonols, isoflavones and stilbenes, as possible responsible for the observed effects of those foods on blood pressure are included. Human intervention studies by using grapes and wine, cocoa and chocolate, black and green tea, soy products, and purified compounds ((+)-catequin, quercetin, (-)-epigallocatechin gallate) are summarized. The discussed hypothesis, strongly supported by experimental data in animals, is that by regulating nitric oxide bioavailability, polyphenols present in fruits and vegetables affect endothelial function and as a consequence, blood pressure. Even when data are not definitive and many questions remain open, the whole evidence is encouraging to start considering diets that can provide benefits to hypertensive subjects, and those benefits will be more significant in people that do not have controlled his/her elevated blood pressure.
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Amelioration of Myocardial Ischemic Reperfusion Injury with Calendula Officinalis
Authors: Diptarka Ray, Subhendu Mukherjee, Mario Falchi, Aldo Bertelli, Pier Carlo Braga and Dipak K. DasCalendula officinalis of family Asteraceae, also known as marigold, has been widely used from time immemorial in Indian and Arabic cultures as an anti-inflammatory agent to treat minor skin wound and infections, burns, bee stings, sunburn and cancer. At a relatively high dose, calendula can lower blood pressure and cholesterol. Since inflammatory responses are behind many cardiac diseases, we sought to evaluate if calendula could be cardioprotective against ischemic heart disease Two groups of hearts were used: the treated rat hearts were perfused with calendula solution at 50 mM in KHB buffer (in mM: sodium chloride 118, potassium chloride 4.7, calcium chloride 1.7, sodium bicarbonate 25, potassium biphosphate 0.36, magnesium sulfate 1.2, and glucose 10) for 15 min prior to subjecting the heart to ischemia, while the control group was perfused with the buffer only. Calendula achived cardioprotection by stimulating left ventricular developed pressure and aortic flow as well as by reducing myocardial infarct size and cardiomyocyte apoptosis. Cardioprotection appears to be achieved by changing ischemia reperfusion-mediated death signal into a survival signal by modulating antioxidant and anti-inflammatory pathways as evidenced by the activation of Akt and Bcl2 and depression of TNFα. The results further strengthen the concept of using natural products in degenerative diseases like ischemic heart disease
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Terminalia arjuna in Cardiovascular Diseases: Making the Transition from Traditional to Modern Medicine in India
Authors: S. K. Maulik and C. K. KatiyarThe stem bark of Terminalia arjuna (Roxb.) is used by the Ayurvedic physicians in India for the treatment of various cardiovascular diseases, collectively referred to as hritroga. It has been extensively studied in animal models to demonstrate cardioprotective properties, ranging from positive inotropic- , hypolipdemic-, coronary vasodilatory- and antioxidant effects to induction of stress protein in heart. Various bioactive compounds, like triterpinoids, tannins, flavonoids and minerals have been isolated from the stem bark. A number of clinical studies have also reported its beneficial effects in patients of chronic stable angina, endothelial dysfunction, heart failure and even ischemic mitral regurgitation. However, there are some identified lacunae, like standardisation of the ‘drug’, toxicity studies along with pharmacological interactions with other drugs and large multicentre randomized clinical trials, before its use by modern medicine is acceptable.
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Cardiac Oxidative Stress and Inflammation are Similar in SAMP8 and SAMR1 Mice and Unaltered by Curcumin and Ginkgo biloba Extract Intake
Chronic inflammation and oxidative stress increase with advancing age and appear to be involved in the pathogenesis of coronary heart disease, the leading cause of death worldwide. There is a need for animal models that reflect the increases in pro-inflammatory cytokines and oxidative damage observed during aging in humans. We therefore aimed to investigate the suitability of the fast-aging senescence-accelerated mouse-prone 8 (SAMP8) strain and its normally aging control senescence-accelerated mouse-resistant 1 (SAMR1) to study the age-dependent changes in cytokines, oxidative damage and antioxidants in the heart. To this end, 2-months-old male SAMR1 and SAMP8 mice were fed a Western type diet (control groups) for 5 months. Two groups of SAMP8 mice were simultaneously fed identical diets fortified with 0.5 g curcumin or 1.0 g Ginkgo biloba extract EGb 761® per kg diet. Heart tissue homogenates were analysed for protein carbonyls, glutathione, glutathione disulfide, methionine, cysteine and uric acid as well as the cytokines tumor-necrosis factor- α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1. Neither the strain (SAMR1 or SAMP8) nor antioxidant intake (curcumin or EGb 761®) affected the concentrations of the measured parameters. In conclusion, our data do not support the suitability of the SAMP8 and SAMR1 strains as a model to study age-related changes in proinflammatory cytokines and oxidative stress parameters in the heart.
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Protective Effect of Natural Antioxidants on Heart Against Ischemia-Reperfusion Damage
Authors: Yan Zhao and Baolu ZhaoThe incidence and mortality of heart disease are the highest among all diseases all over the world, and are still increasing with a world wide rise in living standards. To find effective treatments for prevention and curing heart disease, it is important to understand the mechanisms behind the cause and the development of the disease. Increasing evidences have shown that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in the initiation and progression of heart disease. The potential of using antioxidants, especially the natural antioxidants, in preventing and curing the disease has attracted enormous interest. In this paper we reviewed the progress made in understanding the oxidative stress caused by myocardial ischemia-reperfusion and the cardioprotective effect of natural antioxidants against ischemia-reperfusion injury.
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Squalene as Novel Food Factor
Authors: Hari Narayan Bhilwade, Naoto Tatewaki, Hiroshi Nishida and Tetsuya KonishiCurrently, health beneficial roles of natural products attract much attention and diverse functional ingredients have been extensively studied their preventive effect in many diseases such as cardiovascular diseases and cancer. Squalene is one of those examples. It distributes in nature from plant to animal but extraordinarily concentrated in the liver of certain species of shark (Squalidae family) as it was first identified as a healing substance in the shark liver oil. It is now well-known that squalene is the physiological substance functioning in animal as the precursor of cholesterol biosynthesis. On the other hand, it has long history of using as an attractive resource for functional food, supplement or even pharmaceutics because it has unique physical property and wide variety of physiological functions such as anticancer and anti-hyper cholesterolemia. The antioxidant and oxygen carrying properties of squalene predicts its potential in preventing cardiovascular disease. We reviewed recent progress in functional studies of squalene both in vitro and in vivo models.
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Green Tea Attenuates Cardiovascular Remodeling and Metabolic Symptoms in High Carbohydrate-Fed Rats
Authors: Celestine Rickman, Abishek Iyer, Vincent Chan and Lindsay BrownExcess carbohydrate in the diet may initiate a chronic state of oxidative stress exacerbating the clinical and biochemical symptoms of diet-induced type 2 diabetes, especially glucose intolerance, lipid abnormalities and cardiovascular complications. This study has tested whether green tea, rich in antioxidants, improves both cardiovascular symptoms and glucose intolerance and also reduces oxidative stress in rats fed a high carbohydrate diet. Male 8 week old Wistar rats were fed a diet including fructose and condensed milk (each 40%) for 16 weeks (112 days); control rats were fed corn starch. Green tea-containing food was started from day 1 for the prevention protocol and from day 56 for the reversal protocol. High carbohydrate diet-fed rats showed glucose intolerance, hypertension, mild left ventricular hypertrophy, approximate doubling of cardiac interstitial and perivascular collagen deposition, increased passive diastolic stiffness and increased plasma malondialdehyde concentrations. Administration of green tea to high carbohydrate diet-fed rats prevented and reversed glucose intolerance and the increased systolic blood pressure, left ventricular wet weight, interstitial collagen and passive diastolic stiffness. Plasma malondialdehyde concentrations were also normalized. In summary, treatment with green tea both prevented and reversed the cardiovascular remodeling and metabolic changes seen in high carbohydrate-fed rats suggesting a chronic state of oxidative stress plays a key role in the symptom initiation and progression. Further, green tea may be a useful complementary therapy in diet-induced type 2 diabetes.
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Flavonoid Rich Fraction of Dioscorea bulbifera Linn. (Yam) Enhances Mitochondrial Enzymes and Antioxidant Status, Thereby Protects Heart from Isoproterenol Induced Myocardial Infarction
Authors: K. S. Jayachandran, Hannah R. Vasanthi and G. V. RajamanickamWith recent advances in nutrition sciences, natural products and health-promoting foods have received extensive attention from both health professionals and the common population. The flavonoid rich fraction (FRF) of Dioscorea bulbifera Linn. has a strong free radical scavenging activity. FRF (150 mg/kg) when intervened for a period of 35 days prior to isoproterenol (ISO) challenge to rats maintained the creatine kinase - MB (CK-MB) activity in serum without elevation. Alterations in the antioxidant status in the mitochondria were recognized in the heart tissue of ISO induced rats. ISO induced rats pretreated with FRF (150 mg/kg) ameliorated the lipid peroxidation and thereby enhanced the antioxidant status as evidenced by the increase in the reduced glutathione (GSH) content and the activity of antioxidant enzymes. Moreover, the tricarboxylic acid cycle enzymes such isocitrate dehydrogenase (ICDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH) and α-ketoglutarate dehydrogenase (α-KGDH), which were found decreased in the ISO induced rats showed an enhanced activity in FRF (150 mg/kg) pretreated rats. The activity of NADH dehydrogenase and cytochrome- C-oxidase, the enzymes which transfer the electron in the electron transport chain (ETC) was also increased significantly (p<0.05) in FRF (150 mg/kg) pretreated rats, when compared with ISO induced rats. These results suggest the cardioprotective effect of FRF of Dioscorea bulbifera Linn. in ISO induced MI by attenuating the lipid peroxidation by scavenging free radicals and modulating the energy producing mitochondrial enzymes.
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Antiapoptotic Effect of Novel Compound from Herba leonuri-Leonurine (SCM-198): A Mechanism Through Inhibition of Mitochondria Dysfunction in H9c2 Cells
Authors: Xin Hua Liu, Li Long Pan, Qi Hai Gong and Yi Zhun ZhuApoptosis of cardiomyocytes induced by oxidative stress play a critical role in cardiac dysfunction associated with ventricular remodeling and heart failure. We recently reported that leonurine attenuated hypoxia-induced cardiomyocyte damage. In this study, we investigated the mechanism of leonurine (originally from Herba leonuri but we synthesized it chemically, it as also called SCM-198) in protecting hydrogen peroxide (H2O2)-induced rat embryonic heart-derived H9c2 cells from apoptosis. Exposing H9c2 cells to H2O2 significantly decreased cell viability, and this was attenuated by pretreatment with leonurine for 4 h in a concentration-dependent manner. Meanwhile, leonurine was found to reduce intracellular reactive oxygen species (ROS) generation in H2O2-stimulated cell. Moreover, H9c2 cells stimulated by H2O2 was accompanied with apparent apoptotic characteristics, including fragmentation of DNA, apoptotic body formation, release of cytochrome c, translocation of Bax to mitochondria, loss of mitochondrial membrane potential (Δψm) and activation of caspase 3. Furthermore, H2O2 also induced rapid and significant phosphorylation of the c-Jun-N-terminal kinase 1/2 (JNK1/2), which was inhibited SP600125 (a JNK1/2 inhibitor). All of these events were attenuated by leonurine pretreatment. Taken together, these results demonstrated that leonurine could protect H9c2 cells from H2O2-induced apoptosis via modulation of mitochondrial dysfunction associated with blocking the activation of JNK1/2.
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Restoration of Cardiomyocyte Function in Streptozotocin-Induced Diabetic Rats after Treatment with Vanadate in a Tea Decoction
Diabetes mellitus is associated with abnormal cardiomyocyte Ca2+ transients and contractile performance. We investigated the possibility that an alteration in inositol trisphosphate/phospholipase C (IP3/PLC) signalling may be involved in this dysfunction. Phosphatidic acid stimulates cardiomyocyte contraction through an IP3/PLC signaling cascade. We also tested a novel therapeutic intervention to assess its efficacy in reversing any potential defects. Diabetes was induced in Sprague-Dawley rats by streptozotocin treatment and maintained for an 8 week experimental period. Active cell shortening was significantly depressed in cardiomyocytes obtained from diabetic and insulin-treated diabetic rats in comparison to normal control animals. Perfusion of the cells with phosphatidic acid induced an increase in contraction of control rat cardiomyocytes whereas its effect was inhibitory in cells from streptozotocin-induced diabetic rats. Diabetic rats were also treated orally with vanadate administered in a black tea extract (T/V) for the 8 week period. T/V treatment resulted in a contractile response that was not different from cells of control animals. Furthermore, cardiomyocytes from T/V-treated animals exhibited significantly improved Ca2+ transients in comparison to diabetic animals and exhibited a normalized response to phosphatidic acid perfusion. It is concluded that a T/V glycemic therapy is capable of preventing the defect in IP3/PLC signaling that occurs in diabetes and can restore normal cardiac contractile function.
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Diet and Heart Health: Moderate Wine Drinking Strengthens the Cardioprotective Effects of Fish Consumption
Authors: J. de Leiris, S. Besse and F. BoucherGrowing evidence indicates that the Mediterranean diet is beneficial to human health. Many epidemiological and research studies have reported that this diet pattern is able to limit the development and progression of coronary heart disease, one of the leading cause of morbidity and mortality in both developed and developing countries worldwide. There is now a large consensus about recommending Mediterranean diet to reduce atherosclerosis and coronary artery disease and to limit the risk of fatal complications such as sudden cardiac death and heart failure. This review underlines the role of two of the specific components of the Mediterranean diet, namely marine omega-3 fatty acids and wine, and the link between moderate wine consumption and fatty acid profiles.
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Volumes & issues
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Volume 26 (2025)
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Volume 25 (2024)
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Volume 24 (2023)
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Volume 23 (2022)
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Volume 22 (2021)
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Volume 21 (2020)
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Volume 20 (2019)
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Volume 19 (2018)
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Volume 18 (2017)
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Volume 17 (2016)
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Volume 16 (2015)
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Volume 15 (2014)
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Volume 14 (2013)
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Volume 13 (2012)
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Volume 12 (2011)
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Volume 11 (2010)
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Volume 10 (2009)
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Volume 9 (2008)
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Volume 8 (2007)
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Volume 7 (2006)
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Volume 6 (2005)
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Volume 5 (2004)
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Volume 3 (2002)
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Volume 2 (2001)
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