Biological Activities and Polyphenol Content of Qi Cha Tea®, a Functional Beverage of White Tea Containing Botanicals and Dry Botanical Extracts with European Health Claims.

Infusions of Camellia sinensis leaves have been known for their health benefits. The Bio Concentrate Assets® (ABC) method is a method of enriching organic infusion leaves (from Camellia sinensis) with organic dry and concentrated extracts using organic acacia gum, and its application to white tea has provided Qi cha tea®. In the present study, the content of tea polyphenols and caffeine, and the biochemical properties of Qi cha tea® and its botanical constituents (elderberry, tulsi, Echinacea purpurea, orange peel, lemongrass, and acacia gum) were assessed. Antioxidant and cell viability activities were determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and MTT (3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay in human Caco-2 and HCT-116 cell lines, and ascorbic acid and tamoxifen, respectively. The caffeine and polyphenol composition of Qi cha tea® was modified with less caffeine and gallic acid and more epigallocatechin gallate (EGCG) than the original white tea. The majority of the tested botanical samples including Qi cha tea® at 50 µg/mL show similar antioxidant activities, with the exception of Echinacea purpurea. The greatest effect was found for white tea. The antioxidant power of the Qi cha tea® (90% at 50 µg/mL for pressurized liquid extraction (PLE) was divided by approximately a factor of two (61% at 50 µg/mL for pressurized liquid extraction products (PLEP)), which corresponds to the 48.3% (mass/mass) white tea original content in the Qi cha tea®. Qi cha tea® shows the lowest cytotoxic activity in the viability of the two cell lines when compared to white tea. The application of the ABC method to Qi cha tea® using various botanicals and dry extract with acacia gum as blinder has allowed the development of a new innovative functional health beverage that complies with European health claims.

Effects of long-term anti-ischemic drug treatment on Na,K-ATPase isoforms in cardiomyopathic hamsters.

We investigated the effects of long-term anti-ischemic therapy with trimetazidine on Na,K-ATPase (NKA) activity and protein expression in cardiomyopathy. NKA isoforms in membrane fractions from cardiomyopathic hamsters of the BIO 14.6 strain were studied and compared with those from healthy Syrian golden hamsters (F1B). Trimetazidine was orally administered to a subset of cardiomyopathic hamsters in the early stage of active disease (30 days) until the congestive stage (350 days). In the congestive stage of cardiac failure, the cardiomyopathic hamsters displayed altered NKA activity (-55 % vs. F1B; p<0.01), which was related to a specific decrease in abundance of the membrane NKA ?1 isoform (-27 % vs. F1B). Trimetazidine partially prevented the cardiomyopathy-induced changes in NKA activity (+38 %) and ?1 membrane expression (+ 66 %) without inducing changes in the expression of the ?2 isoform or 1 isoform of NKA. Cardiac hypertrophy and remodeling were reduced after trimetazidine treatment. Additionally, the abundance of NKA ?1 in membranes was negatively correlated with the ventricular weight/body weight ratio (an index of cardiac hypertrophy) (r2 = 0.99; p<0.0015). These findings suggest that some of the cardioprotective effect of trimetazidine during long-term cardiomyopathy may be achieved via regulation of cardiac remodeling and selective modulation cardiac NKA isoforms.

Adenosine and Its Receptors: An Expected Tool for the Diagnosis and Treatment of Coronary Artery and Ischemic Heart Diseases.

Adenosine is an endogenous nucleoside which strongly impacts the cardiovascular system. Adenosine is released mostly by endothelial cells and myocytes during ischemia or hypoxia and greatly regulates the cardiovascular system via four specific G-protein-coupled receptors named A1R, A2AR, A2BR, and A3R. Among them, A2 subtypes are strongly expressed in coronary tissues, and their activation increases coronary blood flow via the production of cAMP in smooth muscle cells. A2A receptor modulators are an opportunity for intense research by the pharmaceutical industry to develop new cardiovascular therapies. Most innovative therapies are mediated by the modulation of adenosine release and/or the activation of the A2A receptor subtypes. This review aims to focus on the specific exploration of the adenosine plasma level and its relationship with the A2A receptor, which seems a promising biomarker for a diagnostic and/or a therapeutic tool for the screening and management of coronary artery disease. Finally, a recent class of selective adenosine receptor ligands has emerged, and A2A receptor agonists/antagonists are useful tools to improve the management of patients suffering from coronary artery disease.

Clinical effects of Lactobacillus strains as probiotics in the treatment of irritable bowel syndrome. Results from the LAPIBSS trial: Future objectives.

The objective of this communication is to present and analyze the recent results from the LAPIBSS study in order to improve future clinical trials on the effects of Lactobacillus strains in the treatment of irritable bowel syndrome (IBS). Using a tightly-controlled clinical trial protocol with the highest Jadad score of 5/5, the current trial aimed to demonstrate the efficacy of a 2-strain mixture of Lactobacillus acidophilus (L. acidophilus) to improve IBS symptoms. Eighty patients diagnosed with IBS according to Rome III criteria were recruited to a multicentric, double-blind, in parallel groups, placebo-controlled, randomized clinical trial. Patients were provided with a daily dose of two capsules containing either two probiotic strains (5 x 109 cfu/capsule) or placebo for 8 weeks. The primary endpoint was abdominal pain score assessed with a 100-mm visual analogue scale (VAS). Secondary endpoints included scores of bloating, flatus and rumbling assessed with a 100-mm VAS, a composite score that consisted of the sum of the 4 VAS scores, and the stool frequency and consistency assessed with the Bristol Stool Form Scale. Our study has failed to demonstrate a significant improvement of the primary endpoint of abdominal pain. Significant differences between groups were observed for flatus score at week 4 (P=0.04) and week 8 (P=0.03) and for composite score at week 8 (P=0.04). The consumption of the 2-strain mixture of L. acidophilus over 8 weeks is safe, significantly decreases flatus and composite scores. The significant effect on flatus could result from the species-specific homofermentative properties of L. acidophilus strains. The negative results on abdominal pain and the gained experience are discussed for the future clinical trials in IBS.

A 2-strain mixture of Lactobacillus acidophilus in the treatment of irritable bowel syndrome: A placebo-controlled randomized clinical trial.

BACKGROUND: In the absence of a well-established therapeutic approach, patients with irritable bowel syndrome seek alternative strategies such as probiotics. AIMS: The current trial named LAPIBSS aimed to demonstrate the efficacy of a 2-strain mixture of Lactobacillus acidophilus to improve irritable bowel syndrome symptoms. METHODS: Eighty patients diagnosed for irritable bowel syndrome were recruited to a multicentre, double-blinded, in parallel groups, placebo-controlled, randomized clinical trial. Patients were provided with a daily dose of two capsules containing either probiotics (5 × 109 cfu/capsule) or placebo for 8 weeks. The primary outcome was abdominal pain score assessed with a 100-mm visual analogue scale. Secondary outcomes included scores of bloating, flatus and rumbling assessed with a 100-mm visual analogue scale, a composite score and bowel habits. RESULTS: Abdominal pain score was significantly improved in both groups at weeks 4 and 8 (P < 0.0001), but no significant differences were found between groups at week 8 (19.0 ±â€¯2.5 vs 25.1 ±â€¯2.6, respectively; LS Means differences = 6.0 ±â€¯3.2; P = 0.06). Significant differences between groups were observed for flatus score at week 4 (P = 0.04) and week 8 (P = 0.03) and composite score (P = 0.04) at week 8. CONCLUSIONS: The consumption of the 2-strain mixture of L. acidophilus over 8 weeks is safe and decreases significantly flatus and composite scores. TRIAL REGISTRATION NUMBER: EudraCT No 2008 A00844-51.

Hyperuricemia and Hypertension, Coronary Artery Disease, Kidney Disease: From Concept to Practice.

Since the publication of the Framingham Heart Study, which suggested that uric acid should no longer be associated with coronary heart disease after additional adjustment for cardiovascular disease risk factors, the number of publications challenging this statement has dramatically increased. The aim of this paper was to review and discuss the most recent studies addressing the possible relation between sustained elevated serum uric acid levels and the onset or worsening of cardiovascular and renal diseases. Original studies involving American teenagers clearly showed that serum uric acid levels were directly correlated with systolic and diastolic pressures, which has been confirmed in adult cohorts revealing a 2.21-fold increased risk of hypertension. Several studies involving patients with coronary artery disease support a role for serum uric acid level as a marker and/or predictor for future cardiovascular mortality and long-term adverse events in patients with coronary artery disease. Retrospective analyses have shown an inverse relationship between serum uric acid levels and renal function, and even a mild hyperuricemia has been shown to be associated with chronic kidney disease in patients with type 2 diabetes. Interventional studies, although of small size, showed that uric acid (UA)-lowering therapies induced a reduction of blood pressure in teenagers and a protective effect on renal function. Taken together, these studies support a role for high serum uric acid levels (>6 mg/dL or 60 mg/L) in hypertension-associated morbidities and should bring awareness to physicians with regards to patients with chronic hyperuricemia.

ABC, a patented innovation in the infusion of teas and herbal plants: enrichment of Camellia sinensis leaves with dry extracts from herbal plants.

Tea and herbal infusions have been known for millennia for their health benefits. However for plants and active ingredients (of mineral and animal origin), it is necessary to consume very large quantities to achieve what is called the health claim dose, i.e., the dose for which the effect on health claim is established. Camellia sinensis leaves is traditionally used as plant infusion. This article aims to review the innovation afforded by the ABC (Bio Concentrate Assets®) patent. The ABC patent has developed an exclusive method of enriching organic tea leaves with organic herbal dry plant extracts using organic acacia gum. This method allows the coupling of concentrated dry extracts from medicinal plants on the Camellia sinensis leave extracts using acacia gum (arabic gum) and to reach to low enough health claim doses thanks to a higher concentration of active ingredients (tested until 10 ingredients). An example of ABC application is provided in a brief overview of manufacturing process for the "Gingo® tea" preparation. The main advantages of the ABC patent application are discussed. In conclusion, the ABC process offers a real breakthrough in the market of teas and herbal teas for health and wellness.

Antioxidant properties of tea blunt ROS-dependent lipogenesis: beneficial effect on hepatic steatosis in a high fat-high sucrose diet NAFLD obese rat model.

Oxidative stress could trigger lipid accumulation in liver and thus hepatic steatosis. Tea is able to prevent liver disorders, but a direct link between antioxidant capacities and prevention of steatosis has not been reported yet. We aimed to investigate such relationship in a rat model of high fat-high sucrose diet (HFS)-induced obesity and to explore more deeply the mechanisms in isolated hepatocytes. Wistar rats were divided into a control group (standard diet), an HFS group (high fat-sucrose diet) and an HFS+tea group (HFS diet with ad-libitum access to tea drink). Body weight, fat mass, glycemic parameters in blood, lipid and oxidative stress parameters in blood and liver were measured in each group after 14 weeks. Isolated hepatocytes were treated with the reactive oxygen species (ROS) inducer t-BHP in the presence or not of antioxidants (tempol or tea), and superoxide anion production and lipid accumulation were measured using specific fluorescent probes. We reported that the HFS diet highly increased hepatic lipids content, while tea consumption attenuated steatosis and improved the oxidative status (decrease in hepatic oxidative stress, increase in plasma total antioxidant capacity). The role of antioxidant properties of tea in such phenomenon was confirmed in primary cultured rat hepatocytes. Indeed, the increase of mitochondrial ROS production with t-BHP resulted in lipid accumulation in hepatocytes (positive linear regression), and antioxidants (tempol or tea) normalized both. We reported that the antioxidant properties of tea protect rats from an obesogenic HFS diet-induced hepatic steatosis by counteracting the ROS-dependent lipogenesis.

Dietary docosahexaenoic acid-enriched glycerophospholipids exert cardioprotective effects in ouabain-treated rats via physiological and metabolic changes.

Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.

Safety of Desmodium adscendens extract on hepatocytes and renal cells. Protective effect against oxidative stress.

AIM: The increased consumption of traditional medicinal plants has been driven by the notion that herbal products are safe and efficient. The purpose of this study was to evaluate the safety and the protective effect of a hydro alcoholic extract of Desmodium adscendens (DA) on liver (HEPG2) and kidney (LLC-PK1) cells. MATERIALS AND METHODS: A hydro alcoholic extract of DA was used. HEPG2 or LLC-PK1 cells were treated with different does of DA, and viability test (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium [MTS]), cytotoxicity assay lactate dehydrogenase (LDH release) and study of the cell morphology were used in order to determine effects of DA on these two cells. RESULTS: A viability test (MTS), a cytotoxicity assay LDH release and a study of the cell morphology revealed that pretreatment with 1 mg/ml or 10 mg/ml DA did not alter viability or LDH release in HEPG2 or LLC-PK1 cells. However, DA at the dose of 100 mg/ml significantly decreased cell viability, by about 40% (P < 0.05). Further, MTS studies revealed that DA 1 mg/ml or 10 mg/ml protected LLC-PK1 cells against a glucose-induced oxidative stress of 24 h (P < 0.05). CONCLUSION: Hence, the lowest concentrations of DA (1 mg/ml and 10 mg/ml) were safe for HEPG2 and LLC-PK1 and protective against an oxidative stress in LLC-PK1 cells. These data suggest that DA extracts used as a traditional herbal as food health supplements should be used at the lowest dosage.

Effect of Brewing Duration on the Antioxidant and Hepatoprotective Abilities of Tea Phenolic and Alkaloid Compounds in a t-BHP Oxidative Stress-Induced Rat Hepatocyte Model.

Tea is an interesting source of antioxidants capable of counteracting the oxidative stress implicated in liver diseases. We investigated the impact of antioxidant molecules provided by a mixture of teas' leaves (green, oolong, pu-erh) after different infusion durations in the prevention of oxidative stress in isolated rat hepatocytes, by comparison with pure epigallocatechin-3-gallate (EGCG), the main representative of tea catechins. Dried aqueous tea extracts (ATE) obtained after 5, 15 and 30 min infusion time were characterized for total polyphenols (gallic acid equivalent), catechins, gallic acid and caffeine (HPLC-DAD/ESI-MS) contents, and for scavenging ability against 2,2-diphenyl-1-picrylhydrazyl free radical. Hepatoprotection was evaluated through hepatocyte viability tests using tert-butyl hydroperoxide as a stress inducer, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, neutral red uptake, real-time cellular impedance) and mitochondrial function tests. We showed that a 5-min incubation time is sufficient for an optimal bioaccessibility of tea compounds with the highest antioxidative ability, which decreases for longer durations. A 4-h pretreatment of cells with ATE significantly prevented cell death by regulating reactive oxygen species production and maintaining mitochondrial integrity. Pure EGCG, at doses similar in ATE (5-12 µM), was inefficient, suggesting a plausible synergy of several water-soluble tea compounds to explain the ATE beneficial effects.

Energetic metabolism during acute stretch-related atrial fibrillation.

BACKGROUND AND METHODS: Perturbations in energetic metabolism and impaired atrial contractility may play an important role in the pathogenesis of atrial fibrillation (AF). Besides, atrial stretch is commonly associated with AF. However, the atrial energetics of stretch-related AF are poorly understood. Here, we measured indicators of energy metabolism during acute stretch-related AF. PCr, adenine nucleotides, and derivatives concentrations as well as the activity of the F(0)F(1)-ATPase and Na,K-ATPase were obtained after 1 h of stretch and/or AF in isolated rabbit hearts and compared to control hearts without stretch and AF. RESULTS: After 1 h of stretch-related AF, the total adenine nucleotides' pool was significantly lower (42.2 +/- 2.6 vs. 63.7 +/- 8.3 micromol/g protein in control group, P < 0.05) and the PCr/ATP ratio significantly higher (2.3 +/- 0.3 vs. 1.1 +/- 0.1 in control group P < 0.05), because of ATP, ADP, and AMP decrease and PCr increase. The sum of high-energy phosphate compounds did not change. There were no significant differences in F(0)F(1)-ATPase nor Na,K-ATPase activity between the groups. CONCLUSIONS: Results show that in this experimental model, acute stretch-related AF induces specific modifications of atrial myocytes energetics that may play a pivotal role in the perpetuation of the arrhythmia.

Remodeling of Na,K-ATPase, and membrane fluidity after atrial fibrillation in sheep.

UNLABELLED: Atrial fibrillation (AF) is accompanied by various changes in ion channels that cause atrial electrophysiological remodeling. The enzyme Na,K-ATPase is also a major cellular mechanism for the regulation of ion homeostasis. During AF, Na,K-ATPase may be regulated by synthesis of its alpha- and beta-subunits as well as changes in membrane fluidity. To test this hypothesis, we studied the effect of pacing-induced AF in sheep on atrial Na,K-ATPase alpha- and beta-subunits and on membrane fluidity as well. METHODS: A group of six sheep (AF group) was subjected to overdrive electrical stimulation of the right atrium in order to induce AF. A group of six sham operated sheep served as control. All paced sheep developed multiple episodes of sustained AF with a mean total duration of 110 min over a 2-hours period. Protein expression of Na,K-ATPase alpha- and beta-subunits in atrial microsomal membranes was assayed by Western blotting analysis. When significant changes in membrane expression were observed, transcriptional regulation was analysed by Northern blotting. Membrane fluidity was assessed on atrial microsomal fractions by anisotropy measurements using the fluorescent probe diphenylhexatriene. RESULTS: Atrial fibrillation enhanced the expression of the Na,K-ATPase beta1-subunit at both membrane and mRNA levels. Anisotropy values were higher in AF group than in control group, indicating a decreased fluidity of the membranes isolated from paced sheep atria. CONCLUSION: These data are the first evidence for an enhanced Na,K-ATPase beta1-subunit expression in membrane during AF. Membrane rigification represents a new factor of tachycardia-induced atrial remodeling.

What is Ginkgo biloba extract EGb 761? An overview--from molecular biology to clinical medicine.

EGb 761 (extract of Ginkgo biloba 761) comes from a single type of tree, a living fossil, the only remaining representative of its phylum; it contains chemical substances unknown in other living things. The flavonoid fraction accounts for 24% of the extract and terpenes (ginkgolides and bilobalide) for 6%. It acts in many different situations and organs, and exerts protective effect on neurodegenerative, sensory, and vascular diseases. In all of these different domains, it has been shown to act at all levels of the organization of life: molecules, cells, tissue, entire organisms, sometimes in particular situations (related to a particular pathology or to senescence) and in humans. Although many questions remain, what stands out in the literature is the overall consistency of the data. Particularly remarkable is that EGb 761 does not exert a specific unidirectional action (activating or inhibiting) in these various domains of physiology and pathology; rather it is regulatory, helping the organism to adapt to the circumstances in which it finds itself.

Ginkgo biloba extract (EGb 761) protects Na,K-ATPase isoenzymes during cerebral ischemia.

Disturbances of Na,K-ATPase activity are implicated in the pathophysiology of cerebral ischemia. Previous experiments have shown that EGb 761 protects NaK-ATPase activity against one hour of cerebral ischemia. In the brain however, the 3 isoenzymes responsible for Na,K-ATPase activity may be differentially affected by various times of ischemia. In the present study, we investigated the effect of a longer period of ischemia, and the protection provided by a pre-treatment with EGb 761 on each of the 3 cerebral NaK-ATPase isoenzymes. In control and EGb 761 pre-treated mice exposed to a 6 hr unilateral occlusion of the middle cerebral artery, Na,K-ATPase activity was decreased by 60% and lipid peroxidation was increased by 40% in the ipsilateral (ischemic) cortex compared to the contralateral one. In parallel, membrane integrity was altered. The alteration of NaK-ATPase activity, as a whole, resulted from a decrease in the activity of the 3 isoenzymes. The two isoenzymes of high ouabain affinity however, had their affinities decreased while the sensitivity of the lowest affinity isoenzyme was increased. Pre-treatment with EGb 761 abolished the differences observed between ipsi- and contralateral cortex, with the exception of the change in ouabain affinity of the low affinity isoenzyme. Ischemia also induced changes in Na,K-ATPase isoenzyme ouabain affinities in the contralateral cortex that where not prevented by EGb 761.