heart-health

Author: Binbin Chen and Guangyi Liu and Peimei Zou and Xing Li and Qiufa Hao and Bei Jiang and Xiangdong Yang and Zhao Hu

Cisplatin (CP)-induced nephrotoxicity hampers its application in clinic. Green tea, particularly its predominant polyphenolic constituent epigallocatechin-3-gallate (EGCG), possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. The present study was designed to investigate the protective effects of EGCG against CP-induced nephrotoxicity in mice. Male C57/BL6 mice in different groups received single injection of CP (20 mg/kg) and EGCG (100 mg/kg) in various sets and kidney tissues and blood were collected after killing. Then, samples were used for biochemical and immunohistochemical assay. Our results showed EGCG decreased biochemical factors and immunohistochemical damage induced by CP. Besides, expression of phosphorylated-extracellular signal-regulated kinase (p-ERK), glucose-regulated protein 78 (GRP78), caspase-12, and apoptosis of kidney were decreased by EGCG via inhibition of endoplasmic reticulum (ER) stress-induced apoptosis.

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Author: Guang Hao and Wei Li and Koon Teo and Xingyu Wang and Jingang Yang and Yang Wang and Lisheng Liu and Salim Yusuf on behalf of INTERHEART China Study Investigators

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Author: Anja Mähler and Jochen Steiniger and Markus Bock and Lars Klug and Nadine Parreidt and Mario Lorenz and Benno F Zimmermann and Alexander Krannich and Friedemann Paul and Michael Boschmann

Background: Muscle weakness and fatigue are common symptoms in multiple sclerosis (MS). Green tea catechins such as (−)epigallocatechin-3-gallate (EGCG) are known to improve energy metabolism at rest and during exercise. Objective: We tested the hypothesis that EGCG improves energy metabolism and substrate utilization in patients with MS. Design: Eighteen patients (8 men) with relapsing-remitting MS (expanded disability status scale score <4.5, all receiving glatiramer acetate) participated in this randomized, double-blind, placebo-controlled, crossover trial at a clinical research center. All patients received EGCG (600 mg/d) and placebo over 12 wk (4-wk washout in between). After each intervention, fasting and postprandial energy expenditure (EE), as well as fat oxidation (FAOx) and carbohydrate oxidation (CHOx) rates, were measured either at rest or during 40 min of exercise (0.5 W/kg). At rest, blood samples and microdialysates from adipose tissue and skeletal muscle were also taken. Results: At rest, postprandial EE and CHOx, as well as adipose tissue perfusion and glucose supply, were significantly lower in men but higher in women receiving EGCG compared with placebo. During exercise, postprandial EE was lower after EGCG than after placebo, indicating an increased working efficiency (men > women). After placebo, exercise EE was mainly fueled by FAOx in both men and women. After EGCG, there was a shift to a higher and more stable CHOx during exercise in men but not in women. Conclusions: Our data indicate that EGCG given to patients with MS over 12 wk improves muscle metabolism during moderate exercise to a greater extent in men than in women, possibly because of sex-specific effects on autonomic and endocrine control. 

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Identification of the Mitochondrial Glutamate Transporter BACTERIAL EXPRESSION, RECONSTITUTION, FUNCTIONAL CHARACTERIZATION, AND TISSUE DISTRIBUTION OF TWO HUMAN ISOFORMS

Author: Giuseppe Fiermonte‡, and Luigi Palmieri‡, and Simona Todisco‡, and Gennaro Agrimi‡, and Ferdinando Palmieri‡§ and John E. Walker

The mitochondrial carriers are a family of transport proteins in the inner membranes of mitochondria. They shuttle substrates, metabolites, and cofactors through this membrane and connect cytoplasm functions with others in the matrix. Glutamate is co-transported with H⁺ (or exchanged for OH⁻), but no protein has ever been associated with this activity. Two human expressed sequence tags encode proteins of 323 and 315 amino acids with 63% identity that are related to the aspartate-glutamate carrier, a member of the carrier family. They have been overexpressed in Escherichia coli and reconstituted into phospholipid vesicles. Their transport properties demonstrate that the two proteins are isoforms of the glutamate/H⁺ symporter described in the past in whole mitochondria. Isoform 1 is expressed at higher levels than isoform 2 in all the tissues except in brain, where the two isoforms are expressed at comparable levels. The differences in expression levels and kinetic parameters of the two isoforms suggest that isoform 2 matches the basic requirement of all tissues especially with respect to amino acid degradation, and isoform 1 becomes operative to accommodate higher demands associated with specific metabolic functions such as ureogenesis.

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Author: Wiley W. Souba and Ming Pan and Bruce R. Stevens

Author: Desai MJ, and Gill MS, and Hsu WH, and Armstrong DW

Theanine, first discovered in tea, is a chiral nonproteinic amino acid that has been reported to have cardiovascular, neurological, and oncological effects. It is being considered as a therapeutic/medicinal agent and additive in consumer products. The present study evaluated the pharmacokinetics of d-theanine, l-theanine, and d,l-theanine in plasma and urine using LC-ESI/MS in rats after oral (p.o.) and intraperitoneal (i.p.) administration. Oral administration data indicated that gut absorption of d-theanine was far less than that of l-theanine. However, after i.p. administration, plasma theanine concentrations of l- and d-theanine were similar. This indicated that d- and l-theanine may exhibit a competitive effect with respect to intestinal absorption. Regardless of the route of administration, p.o. or i.p., the presence of the other enantiomer always decreased theanine plasma concentrations, indicating d,l-theanine competition with respect to urinary reabsorption. Data on urinary concentrations of d-theanine suggested that the d-isomer may be eliminated with minimal metabolism. l-Theanine appeared to be preferentially reabsorbed and metabolized by the kidney while d-theanine was preferentially excreted. Clearly, the bioequivalencies of d,l-theanine and its enantiomers were found to be quite different from one another. Consequently, the efficacy of commercial theanine products containing d-theanine, l-theanine, or d,l-theanine may be quite different. 

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Author: T. Giesbrecht, and J.A. Rycroft, and M.J. Rowson and E.A. De Bruin

The non-proteinic amino acid L-theanine and caffeine, a methylxanthine derivative, are naturally occurring ingredients in tea. The present study investigated the effect of a combination of 97 mg L-theanine and 40 mg caffeine as compared to placebo treatment on cognitive performance, alertness, blood pressure, and heart rate in a sample of young adults (n = 44). Cognitive performance, self-reported mood, blood pressure, and heart rate were measured before L-theanine and caffeine administration (i.e. at baseline) and 20 min and 70 min thereafter. The combination of moderate levels of L-theanine and caffeine significantly improved accuracy during task switching and self-reported alertness (both P < 0.01) and reduced self-reported tiredness (P < 0.05). There were no significant effects on other cognitive tasks, such as visual search, choice reaction times, or mental rotation. The present results suggest that 97 mg of L-theanine in combination with 40 mg of caffeine helps to focus attention during a demanding cognitive task.

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Author: Siamwala JH, and Dias PM, and Majumder S, and Joshi MK, and Sinkar VP, and Banerjee G, and Chatterjee S

Consumption of tea (Camellia sinensis) improves vascular function and is linked to lowering the risk of cardiovascular disease. Endothelial nitric oxide is the key regulator of vascular functions in endothelium. In this study, we establish that l-theanine, a non-protein amino-acid found in tea, promotes nitric oxide (NO) production in endothelial cells. l-theanine potentiated NO production in endothelial cells was evaluated using Griess reaction, NO sensitive electrode and a NO specific fluorescent probe (4-amino-5-methylamino-2',7'-difluororescein diacetate). l-Theanine induced NO production was partially attenuated in presence of l-NAME or l-NIO and completely abolished using eNOS siRNA. eNOS activation was Ca(2+) and Akt independent, as assessed by fluo-4AM and immunoblotting experiments, respectively and was associated with phosphorylation of eNOS Ser 1177. eNOS phosphorylation was inhibited in the presence of ERK1/2 inhibitor, PD-98059 and partially inhibited by PI3K inhibitor, LY-294002 and Wortmanin suggesting PI3K-ERK1/2 dependent pathway. Increased NO production was associated with vasodilation in ex ovo (chorioallantoic membrane) model. These results demonstrated that l-theanine administration in vitro activated ERK/eNOS resulting in enhanced NO production and thereby vasodilation in the artery. The results of our experiments are suggestive of l-theanine mediated vascular health benefits of tea.

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Author: Mario Lorenz and Janka Urban and Ulrich Engelhardt and Gert Baumann and Karl Stangl and Verena Stangl

Epidemiological studies suggest that consumption of tea is associated with beneficial cardiovascular effects. Since different types of tea are consumed throughout the world, a question of much interest is whether green tea is superior to black tea in terms of cardiovascular protection. We therefore compared the effects of green and black tea on nitric oxide (NO) production and vasodilation and elucidated the tea compounds involved. We chose a highly fermented black tea and determined concentrations of individual tea compounds in both green and black tea of the same type (Assam). The fermented black tea was almost devoid of catechins. However, both teas stimulated eNOS activity and phosphorylation in bovine aortic endothelial cells (BAEC) as well as vasorelaxation in rat aortic rings to a similar extent. In green tea, only epigallocatechin-3-gallate (EGCG) resulted in pronounced NO production and NO-dependent vasorelaxation in aortic rings. During tea processing to produce black tea, the catechins are converted to theaflavins and thearubigins. Individual black tea theaflavins showed a higher potency than EGCG in NO production and vasorelaxation. The thearubigins in black tea are highly efficient stimulators of vasodilation and NO production. Green and black tea compounds induced comparable phosphorylation of eNOS and upstream signalling kinases. Whereas stimulation of eNOS activity by EGCG was only slightly affected by pretreatment of cells with various ROS scavengers, TF3(theaflavin-3′,3-digallate)-induced eNOS activity was partially inhibited by PEG-catalase. These results implicate that highly fermented black tea is equally potent as green tea in promoting beneficial endothelial effects. Theaflavins and thearubigins predominantly counterbalance the lack of catechins in black tea. The findings may underline the contribution of black tea consumption in prevention of cardiovascular diseases.

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Author: Ulrike Peters, and Charles L Poole, and Lenore Arab

This meta-analysis of tea consumption in relation to stroke, myocardial infarction, and all coronary heart disease is based on 10 cohort studies and seven case-control studies. The study-specific effect estimates for stroke and coronary heart disease were too heterogeneous to be summarized (homogeneity p < 0.02 for stroke, p < 0.001 for coronary heart disease). Only the relative risk estimates for myocardial infarction (seven studies) appeared reasonably homogeneous (homogeneity p = 0.20). The incidence rate of myocardial infarction is estimated to decrease by 11% with an increase in tea consumption of 3 cups per day (fixed-effects relative risk estimate = 0.89, 95% confidence interval: 0.79, 1.01) (1 cup = 237 ml). However, evidence of bias toward preferential publication of smaller studies that suggest protective effects urges caution in interpreting this result. The geographic region where the studies were conducted appeared to explain much of the heterogeneity among coronary heart disease, myocardial infarction, and probably stroke results. With increasing tea consumption, the risk increased for coronary heart disease in the United Kingdom and for stroke in Australia, whereas the risk decreased in other regions, particularly in continental Europe.

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