In vitro Bioaccessibility, Bioavailability, and Plasma Protein Interaction of New Oral Anticoagulants in the Presence of Macronutrients.

BACKGROUND: Over the last years, a new generation of oral anticoagulants (NOACs), including apixaban, rivaroxaban and dabigatran, has been developed for the control of thrombosis and related disorders. The presence of food within the gastrointestinal (GI) tract can potentially affect the oral bioavailability of drugs. OBJECTIVE: In the present paper, we evaluated the stability of these drugs in in vitro GI digestion, with and without the main macronutrients such as proteins, lipids, carbohydrates, and fibers, and their ability to enter into the systemic circulation. In addition, we examined the percentage of the drug binding to plasma proteins, such as human serum albumin, high density- and low density lipoproteins. METHODS: The NOACs bioaccessibility was evaluated by an in vitro procedure simulating the gastrointestinal enzymatic system, while their bioavailability was studied by cell culture of Caco-2 cells and in vitro study of transepithelial transport. The in vitro transepithelial permeated NOACs were added to plasma protein solutions simulating the average fasting plasma protein concentrations. The NOACs detection was carried out by HPLC-DAD/ESI-MS analysis. RESULTS: GI digestion significantly reduces intestinal bioaccessibility and bioavailability of NOACs, especially as regards apixaban and dabigatran. Interestingly, the co-digestion of fibers led to a strong decrease of NOAC intestinal bioaccessibility and bioavailability, while the effects of the other macronutrients, as well as a low fiber standard meal, had no significant influence in this sense. CONCLUSION: Dabigatran, rivaroxaban and apixaban may be administered independently of a standard meal, provided that it does not include a high amount of dietary fibers.

Effects of Tea and Coffee Consumption on Cardiovascular Diseases and Relative Risk Factors: An Update.

BACKGROUND: Tea and coffee are the second and third most consumed beverages after water, respectively. The high consumption of these beverages is due to the sensorial properties and effects on psychological and physiological functions, induced by caffeine and many other bioactive components responsible for the protective effects on human health generally ascribed to these beverages. METHODS: The goal of this review article is to collect the scientific data obtained from clinical trials published in the last five years on the role of tea and coffee consumption against cardiovascular diseases (CVDs) and CVD risk factors such as hypertension, hyperglicemia, and hyperlipidaemia. RESULTS: In normal weight subjects, clinical trials showed that the consumption of tea is inversely associated to CVD risk factors or no association was found. Differently, in overweight subjects, the clinical trials and the metaanalyses showed an inverse correlation between tea consumption and CVDs. As regards coffee, it has long been suspected to be associated to high risk of CVDs. Nevertheless, some recent investigations reported that moderate coffee consumption have no effect or even protective effects against CVDs risk factors. The results of the metaanalyses confirm this trend suggesting that moderate coffee drinkers could be associated to a lower risk of CVDs than non- or occasional coffee drinkers or no association can be demonstrated between coffee consumption and CVDs. CONCLUSION: Literature data on tea consumption and CVD risk factors support that tea consumption reduces some risk factors especially in overweight people and obese subjects. Therefore, these results seem to suggest that tea could exert a protective effects against CVD development. As regards coffee, the results are controversial and did not allow to draw conclusions. Therefore, further research is needed before definitive recommendations for coffee consumption against CVD development can be made.

Effect of Red Wine Polyphenols on the Expression of Transthyretin in Murine Choroid Plexus.

Plasmatic transthyretin may be regarded as a suitable candidate biomarker for the onset, severity, and progression of Alzheimer disease. The aim of the present experimental work was to evaluate the effect of red wine polyphenols (RWPs) on the expression of transthyretin in murine choroid plexus. In contrast to what generally reported in literature for polyphenols, our experimental results indicated a correlation between RWPs assumption and a decrease of transthyretin expression, with a non-dose dependent trend. The present study would point out the attention on the possible pro-oxidant effects of red wine polyphenols at certain doses, although further in vitro, in vivo, and clinical experiments must be performed in order to clarify the mechanisms of action at the base of observed results.

Improving of nutraceutical features of many important mediterranean vegetables by inoculation with a new commercial product.

Several epidemiological studies show that fruits, vegetables and cereals can play a nutraceutical role for their content of many antioxidant phytochemicals such as carotenoids, ascorbic acid and phenolics. A commercial inoculant (MICOSAT F(®)) containing arbuscular mycorrhizal fungi (AMF) could improve the nutritional value in crops. The goal of this work was to evaluate the effect of AMF on the production level of carotenoids, AsA, phenols including antocyanins and saponins, proteins, total antioxidant activity and nitrates in fruits, vegetables, legumes and durum wheat var. grecale, whose consumption is largely recommended according to Mediterranean diet. The treatment increased the antioxidant activity in strawberries (37.50%), in giant lentils (29.17%) and in durum wheat (63.63%) but decreased it in kiwi (31.81%) and in grape (19.81%). Nitrate levels decreased significantly in strawberries (39.78%) and in tomato intended for transformation (37.79%). The application of MICOSAT F(®) enhanced the levels of several secondary metabolites. However, the amount of phytochemicals and respective by-products were reduced in some cases. Environmental conditions and modality of AMF inoculation could module both primary and secondary metabolites.

Exploring the nutraceutical potential of polyphenols from black, green and white tea infusions - an overview.

Black, green, and white teas are the main commercial teas obtained from buds and leaves of Camellia sinensis (L.). The postharvest processing treatments, together with genotype and growing techniques, may strongly affect the chemical composition of the tea infusion and, thereby, its potential effects on health. Catechins constituted up to 30% of tea leaves dry weight. During fermentation, polyphenols undergo enzymatic oxidation, leading to the formation of condensed polymeric compounds regarded as responsible for the typical organoleptic properties of black tea leaves and related infusions. Scientific studies has been recently focusing on the possibility that tea polyphenols, particularly those of black and green tea, may lead to healthy properties in individuals affected by diseases correlated to metabolic syndrome. In vivo experiments reveal that green and black tea polyphenols may be able to reduce hyperglycemia and insulin resistance. Other works suggest that black tea polymeric products may be effective in decreasing blood cholesterol levels and hypertriacylglycerolemia. To this regard, very few data about white tea, being the rarest and the least handled tea, are available so far. It has been reported that white tea could show higher antioxidative capacity than green tea and to exert in vitro lipolytic activity. Considering the increasing interest towards healthy potential through diet and natural medicaments, the aim of the present review was to overview the nutraceutical potential of polyphenols from tea after various degrees of fermentation.

Naringenin and atherosclerosis: a review of literature.

Atherosclerosis is a multifactorial disease mainly caused by deposition of low-density lipoprotein (LD) cholesterol in macrophages of arterial walls. Atherosclerosis leads to heart attacks as well as stroke. Epidemiological studies showed that there is an inverse correlation between fruit and vegetable consumption and the risk of atherosclerosis. The promising effect of high vegetable and fruit containing diet on atherosclerosis is approved by several experimental studies on isolated phytochemicals such as flavonoids. Flavonoids are known to up-regulate endogenous antioxidant system, suppress oxidative and nitrosative stress, decrease macrophage oxidative stress through cellular oxygenase inhibition as well as interaction with several signal transduction pathways and from these ways, have therapeutic effects against atherosclerosis. Naringenin is a well known flavonoid belonging to the chemical class of flavanones. It is especially abundant in citrus fruits, especially grapefruits. A plethora of evidences ascribes to naringenin antiatherosclerotic effects. Naringenin abilities to decrease LDL and triglycerides as well as inhibit glucose uptake; increase high-density lipoprotein (HDL); co-oxidation of NADH; suppress protein oxidation; protect against intercellular adhesion molecule-1(ICAM-1); suppress macrophage inflammation; inhibit leukotriene B4, monocyte adhesion and foam cell formation; induce of HO-1 and G 0/G 1 cell cycle arrest in vascular smooth muscle cells (VSMC) and down regulate atherosclerosis related genes are believed to have crucial role in the promising role against atherosclerosis. In the present review, we have summarized the available literature data on the anti-atherosclerotic effects of naringenin and its possible mechanisms of action.