Cardioprotective Properties of Phenolic Compounds: A Role for Biological Rhythms.

Cardiovascular diseases (CVD) are the leading cause of deaths worldwide and their prevalence is continuously increasing. Available treatments may present several side effects and therefore the development of new safer therapeutics is of interest. Phenolic compounds have shown several cardioprotective properties helpful in reducing different CVD risk factors such as inflammation, elevated blood pressure, hyperlipidemia, or endothelial dysfunction.

Time-of-Day Circadian Modulation of Grape-Seed Procyanidin Extract (GSPE) in Hepatic Mitochondrial Dynamics in Cafeteria-Diet-Induced Obese Rats.

Major susceptibility to alterations in liver function (e.g., hepatic steatosis) in a prone environment due to circadian misalignments represents a common consequence of recent sociobiological behavior (i.

Dietary proanthocyanidins modulate melatonin levels in plasma and the expression pattern of clock genes in the hypothalamus of rats.

Scope: Circadian rhythms allow organisms to anticipate and adapt to environmental changes, and food components can adjust internal rhythms. Proanthocyanidins improve cardiovascular risk factors that exhibit circadian oscillations. Therefore, the aim of the current study was to determine whether proanthocyanidins can modulate body rhythms.

Grape seed proanthocyanidin extract improves the hepatic glutathione metabolism in obese Zucker rats.

Scope: Increased oxidative stress may play an important role in metabolic syndrome and related manifestations, including obesity, atherosclerosis, hypertension, and insulin resistance. Its relation to obesity is due to increased reactive oxygen species and/or decreased glutathione (GSH) antioxidant metabolism. Consequently, the activation of glutathione metabolism appears to be a central defense response to prevent oxidative stress.

Differential modulation of apoptotic processes by proanthocyanidins as a dietary strategy for delaying chronic pathologies.

Apoptosis is a biological process necessary for maintaining cellular homeostasis. Several diseases can result if it is deregulated. For example, inhibition of apoptotic signaling pathways is linked to the survival of pathological cells, which contributes to cancer, whereas excessive apoptosis is linked to neurodegenerative diseases, partially via oxidative stress.

Grape seed procyanidin extract reduces the endotoxic effects induced by lipopolysaccharide in rats.

Acute inflammation is a response to injury, infection, tissue damage, or shock. Bacterial lipopolysaccharide (LPS) is an endotoxin implicated in triggering sepsis and septic shock, and LPS promotes the inflammatory response, resulting in the secretion of proinflammatory and anti-inflammatory cytokines such as the interleukins (IL-6, IL-1β, and IL-10) and tumor necrosis factor-α by the immune cells. Furthermore, nitric oxide and reactive oxygen species levels increase rapidly, which is partially due to the activation of inducible nitric oxide synthase in several tissues in response to inflammatory stimuli.

Identification of PPARgamma partial agonists of natural origin (II): in silico prediction in natural extracts with known antidiabetic activity.

Background: Natural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action.

Methodology/principal Findings: From an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally), we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ) partial agonists 12 molecules from 11 extracts known to have antidiabetic activity.

miRNAs, polyphenols, and chronic disease.

MicroRNAs (miRNAs) are small noncoding RNAs, approximately 18-25 nucleotides in length, that modulate gene expression at the posttranscriptional level. Thousands of miRNAs have been described, and it is thought that they regulate some aspects of more than 60% of all human cell transcripts. Several polyphenols have been shown to modulate miRNAs related to metabolic homeostasis and chronic diseases.

Identification of human IKK-2 inhibitors of natural origin (Part II): in Silico prediction of IKK-2 inhibitors in natural extracts with known anti-inflammatory activity.

Human inhibitor NF-κB kinase 2 (hIKK-2) is the primary component responsible for activating NF-κB in response to various inflammatory stimuli. Thus, synthetic ATP-competitive inhibitors for hIKK-2 have been developed as anti-inflammatory compounds. We recently reported a virtual screening protocol (doi:10.

Nutritional biomarkers and foodomic methodologies for qualitative and quantitative analysis of bioactive ingredients in dietary intervention studies.

Traditional dietary assessment methods, such as 24-h recalls, weighted food diaries and food frequency questionnaires (FFQs) are highly subjective and impair the assessment of successfully accomplished dietary interventions. Foodomic technologies offer promising methodologies for gathering scientific evidence from clinical trials with sensitive methods (e.g.

Identification of human IKK-2 inhibitors of natural origin (part I): modeling of the IKK-2 kinase domain, virtual screening and activity assays.

Background: Their large scaffold diversity and properties, such as structural complexity and drug similarity, form the basis of claims that natural products are ideal starting points for drug design and development. Consequently, there has been great interest in determining whether such molecules show biological activity toward protein targets of pharmacological relevance. One target of particular interest is hIKK-2, a serine-threonine protein kinase belonging to the IKK complex that is the primary component responsible for activating NF-κB in response to various inflammatory stimuli.

Hypolipidemic effects of proanthocyanidins and their underlying biochemical and molecular mechanisms.

Proanthocyanidins are the most abundant polyphenols in human diets. Epidemiological studies strongly suggest that proanthocyanidins protect against cardiovascular diseases. Despite the antioxidant and anti-inflammatory properties of these flavonoids, one of the mechanisms by which proanthocyanidins exert their cardiovascular protection is improving lipid homeostasis.

Determination of procyanidins and their metabolites in plasma samples by improved liquid chromatography-tandem mass spectrometry.

An off-line solid-phase extraction (SPE) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for determining procyanidins, catechin, epicatechin, dimer, and trimer in plasma samples. In the validation procedure of the analytical method, linearity, precision, accuracy, detection limits (LODs), quantification limits (LOQs), and the matrix effect were studied. Recoveries of the procyanidins were higher than 84%, except for the trimer, which was 65%.

Grape seed procyanidins inhibit the expression of metallothione in genes in human HepG2 cells.

Procyanidins are the most abundant polyphenols in red wine and are also found in cereals, fruits, chocolate and tea. They exert many beneficial health effects, especially on the cardiovascular system (Bagchi et al. in Mutat Res 523-524:87-97, 2003; Williams et al.

Dietary procyanidins lower triglyceride levels signaling through the nuclear receptor small heterodimer partner.

Hypertriglyceridemia is an independent risk factor in the development of cardiovascular diseases, and we have previously reported that oral administration of a grape seed procyanidin extract (GSPE) drastically decreases plasma levels of triglycerides (TG) and apolipoprotein B (ApoB) in normolipidemic rats, with a concomitant induction in the hepatic expression of the nuclear receptor small heterodimer partner (NR0B2/SHP). Our objective in this study was to elucidate whether SHP is the mediator of the reduction of TG-rich ApoB-containing lipoproteins triggered by GSPE. We show that GSPE inhibited TG and ApoB secretion in human hepatocarcinoma HepG2 cells and had and hypotriglyceridemic effect in wild-type mouse.

Moderate red-wine consumption partially prevents body weight gain in rats fed a hyperlipidic diet.

Red wine is a beverage that can exert a broad spectrum of health-promoting actions both in humans and laboratory animal models if consumed moderately. However, information about its effect on body weight is scarce. We have evaluated the effect of moderate red wine consumption on body weight and energy intake in male Zucker lean rats fed a hypercaloric diet for 8 weeks.

Grape seed procyanidins improve atherosclerotic risk index and induce liver CYP7A1 and SHP expression in healthy rats.

Moderate consumption of red wine reduces risk of death from cardiovascular disease. The polyphenols in red wine are ultimately responsible for this effect, exerting antiatherogenic actions through their antioxidant capacities and modulating intracellular signaling pathways and transcriptional activities. Lipoprotein metabolism is crucial in atherogenesis, and liver is the principal organ controlling lipoprotein homeostasis.