Grape-Seed Proanthocyanidin Extract Reverts Obesity-Related Metabolic Derangements in Aged Female Rats.

Obesity and ageing are current issues of global concern. Adaptive homeostasis is compromised in the elderly, who are more likely to suffer age-related health issues, such as obesity, metabolic syndrome, and cardiovascular disease. The current worldwide prevalence of obesity and higher life expectancy call for new strategies for treating metabolic disorders.

A Ten-Day Grape Seed Procyanidin Treatment Prevents Certain Ageing Processes in Female Rats over the Long Term.

Adaptive homeostasis declines with age and this leads to, among other things, the appearance of chronic age-related pathologies such as cancer, neurodegeneration, osteoporosis, sarcopenia, cardiovascular disease and diabetes. Grape seed-derived procyanidins (GSPE) have been shown to be effective against several of these pathologies, mainly in young animal models. Here we test their effectiveness in aged animals: 21-month-old female rats were treated with 500 mg GSPE/kg of body weight for ten days.

Protective Effect of Proanthocyanidins in a Rat Model of Mild Intestinal Inflammation and Impaired Intestinal Permeability Induced by LPS.

Scope: Intestinal dysfunction consists of a defective barrier function, which allows the influx of luminal endotoxins, thus causing intestinal inflammation. Proanthocyanidins are natural bioactive compounds that could modulate intestinal dysfunction. This study analyzes the protective effects of proanthocyanidins in a rat model of intestinal dysfunction.

The co-administration of proanthocyanidins and an obesogenic diet prevents the increase in intestinal permeability and metabolic endotoxemia derived to the diet.

The consumption of Westernized diets leads to hyperphagia and obesity, as well as intestinal alterations. In the present study, we evaluated the effect of the administration of a grape seed proanthocyanidin extract (GSPE) at different time points on the modulation of intestinal barrier function (intestinal permeability and metabolic endotoxemia), in rats with high-fat/high-carbohydrate diet-induced obesity. Animals were fed a cafeteria diet (CAF) supplemented with a preventive (PRE-CAF) or simultaneously intermittent (SIT-CAF) GSPE treatment (500 mg/kg bw).

Novel ex Vivo Experimental Setup to Assay the Vectorial Transepithelial Enteroendocrine Secretions of Different Intestinal Segments.

The enteroendocrine system coordinates gastrointestinal (GI) tract functionality and the whole organism. However, the scarcity of enteroendocrine cells and their scattered distribution make them difficult to study. Here, we glued segments of the GI wall of pigs to a silicon tube, keeping the apical and the basolateral sides separate.

Epoxygenase inactivation exacerbates diet and aging-associated metabolic dysfunction resulting from impaired adipogenesis.

Objective: When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established. The exact contribution of the P450 epoxygenase pathway, however, remains to be established.

Chronic supplementation with dietary proanthocyanidins protects from diet-induced intestinal alterations in obese rats.

Scope: Increased attention has been paid to the link between altered intestinal function and elevated incidence of metabolic disorders, such as in obesity. This study investigated in obese rats the role of grape seed proanthocyanidin extract (GSPE) chronic treatment, taken in a low, moderate, or high dose, on obesity-associated intestinal alterations in response to a cafeteria diet (CAF).

Methods And Results: To evaluate the degree of intestinal inflammation, reactive oxygen species (ROS) production and myeloperoxidase (MPO) activity were measured as well as the expression of inflammatory-related genes.

Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity.

Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases.

Effects of flavanols on the enteroendocrine system: Repercussions on food intake.

Flavanols are plant-derived bioactive compounds for which several beneficial effects have been described. When ingested, they reach the gastrointestinal tract, where they can interact with the enteroendocrine cells. In this paper, we consider the possibility that flavanols modulate enterohormone secretion.

Defining Conditions for Optimal Inhibition of Food Intake in Rats by a Grape-Seed Derived Proanthocyanidin Extract.

Food intake depends on homeostatic and non-homeostatic factors. In order to use grape seed proanthocyanidins (GSPE) as food intake limiting agents, it is important to define the key characteristics of their bioactivity within this complex function. We treated rats with acute and chronic treatments of GSPE at different doses to identify the importance of eating patterns and GSPE dose and the mechanistic aspects of GSPE.

Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet.

Obesity has reached pandemic levels worldwide. The current models of diet-induced obesity in rodents use predominantly high-fat based diets that do not take into account the consumption of variety of highly palatable, energy-dense foods that are prevalent in Western society. We and others have shown that the cafeteria (CAF) diet is a robust and reproducible model of human metabolic syndrome with tissue inflammation in the rat.

Antioxidant effects of proanthocyanidin-rich natural extracts from grape seed and cupuassu on gastrointestinal mucosa.

Background: The gastrointestinal tract (GI) is constantly exposed to reactive species released by the GI tract itself, and those present in food and beverages. Phenolic compounds may help in protecting the GI tract against damage produced by the reactive species. In this paper we have analyzed the effects of a grape seed proanthocyanidin extract (GSPE) on reactive oxygen species (ROS) production in two different intestinal cell types: the absorptive cell line Caco-2 and the enteroendocrine cell line STC-1.

Procyanidin B2 inhibits inflammasome-mediated IL-1β production in lipopolysaccharide-stimulated macrophages.

Scope: Macrophage stimulation with bacterial LPS triggers inflammasome activation, resulting in pro-inflammatory IL-1β cytokine maturation and secretion. IL-1β underlies the pathologies of many diseases, including type-2 diabetes. Thus, the modulation of the inflammatory response through bioactive food compounds, such as procyanidins, is a powerful tool to promote homeostasis.

Procyanidins and their healthy protective effects against type 2 diabetes.

This review focuses on the role of procyanidins, the main group of flavonoids, on type 2 diabetes mellitus (T2DM) and insulin resistance. We compile the role of procyanidins on several animal models, and we evaluate their effects on target tissues and analyze the mechanisms involved. Procyanidin treatments in fructose or high-fat induced insulin resistant models were found to improve the damage induced by the diet, thus improving glycemia and insulin sensitivity.

A grape seed extract increases active glucagon-like peptide-1 levels after an oral glucose load in rats.

We have previously reported that procyanidins, a class of flavonoids, improve glycemia and exert an incretin-like effect, which was linked to their proven inhibitory effect on the dipeptidyl-peptidase 4 (DPP4) activity. However, their actual effect on incretin levels has not been reported yet. Therefore, in the present study we have evaluated whether a grape seed extract enriched in procyanidins (GSPE) modulates plasma incretin levels and attempted to determine the mechanisms involved.

Grape-seed procyanidins prevent the cafeteria-diet-induced decrease of glucagon-like peptide-1 production.

Grape-seed procyanidin extract (GSPE) has been reported to improve insulin resistance in cafeteria rats. Because glucagon-like peptide-1 (GLP-1) is involved in glucose homeostasis, the preventive effects of GSPE on GLP-1 production, secretion, and elimination were evaluated in a model of diet-induced insulin resistance. Rats were fed a cafeteria diet for 12 weeks, and 25 mg of GSPE/kg of body weight was administered concomitantly.

Grape-seed procyanidins modulate cellular membrane potential and nutrient-induced GLP-1 secretion in STC-1 cells.

Grape-seed procyanidin extracts (GSPE) modulate glucose homeostasis, and it was suggested that GSPE may achieve this by enhancing the secretion of incretin hormones such as glucagon-like peptide-1 (GLP-1). Therefore, the aim of the present study is to examine in detail the effects of GSPE on intestinal endocrine cells (STC-1). GSPE was found to modulate plasma membrane potential in enteroendocrine cells, inducing depolarization at low concentrations (0.

Gallic acid is an active component for the anticarcinogenic action of grape seed procyanidins in pancreatic cancer cells.

The aim of the present work was to evaluate the effects of a grape seed procyanidin extract (GSPE) on proliferation and apoptosis in the pancreatic adenocarcinoma cell line MIA PaCa-2 and identify the components of the extract with higher activity. The effects of the extract were analyzed on the proliferation and apoptosis processes in MIA PaCa-2 cells, as well as in the levels of the apoptosis markers Bcl-2 and Bax, the mitochondrial membrane potential, and reactive oxygen species levels. Finally, the components of the extract with higher effects were elucidated using enriched fractions of the extract and pure compounds.

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.

Grape Seed Procyanidin Extract Improves Insulin Production but Enhances Bax Protein Expression in Cafeteria-Treated Male Rats.

In a previous study, the administration of a grape seed procyanidin extract (GSPE) in female Wistar rats improved insulin resistance, reduced insulin production, and modulated apoptosis biomarkers in the pancreas. Considering that pharmacokinetic and pharmacodynamic parameters in females are different from these parameters in males, the aim of the present study was to evaluate the effects of GSPE on male Wistar cafeteria-induced obese rats. The results have confirmed that the cafeteria model is a robust model mimicking a prediabetic state, as these rats display insulin resistance, increased insulin synthesis and secretion, and increased apoptosis in the pancreas.

Grape seed procyanidin extract modulates proliferation and apoptosis of pancreatic beta-cells.

Grape seed procyanidin extract (GSPE) modulates glucose homeostasis and insulinemia in several animal models. Under pathological conditions, insulin levels are dependent on pancreatic beta-cell functionality, as well as on the beta-cell mass expansion or apoptosis in the pancreas. In this study, we analysed the effects of GSPE on modulating apoptosis and proliferation in beta-cells.

Procyanidins modulate microRNA expression in pancreatic islets.

Procyanidins modulate glucose metabolism, partly due to its effects on pancreas. Given the role of microRNAs (miRNAs) in the regulation of diabetes and the fact that flavonoids modulate miRNAs in other tissues, we hypothesized that procyanidins might target miRNAs in the pancreas. We investigated the miRNA expression profile in pancreatic islets isolated from rats treated with a daily dose of grape seed procyanidin extract (GSPE) (25 mg/kg of body weight) for 45 days.

Identification of novel human dipeptidyl peptidase-IV inhibitors of natural origin (Part II): in silico prediction in antidiabetic extracts.

Background: Natural extracts play an important role in traditional medicines for the treatment of diabetes mellitus and are also an essential resource for new drug discovery. Dipeptidyl peptidase IV (DPP-IV) inhibitors are potential candidates for the treatment of type 2 diabetes mellitus, and the effectiveness of certain antidiabetic extracts of natural origin could be, at least partially, explained by the inhibition of DPP-IV.

Methodology/principal Findings: Using an initial set of 29,779 natural products that are annotated with their natural source and an experimentally validated virtual screening procedure previously developed in our lab (Guasch et al.

Grape seed procyanidins improve β-cell functionality under lipotoxic conditions due to their lipid-lowering effect.

Procyanidins have positive effects on glucose metabolism in conditions involving slightly disrupted glucose homeostasis, but it is not clear how procyanidins interact with β-cells. In this work, we evaluate the effects of procyanidins on β-cell functionality under an insulin-resistance condition. After 13 weeks of cafeteria diet, female Wistar rats were treated with 25 mg of grape seed procyanidin extract (GSPE)/kg of body weight (BW) for 30 days.

Pancreatic islet proteome profile in Zucker fatty rats chronically treated with a grape seed procyanidin extract.

Grape seed procyanidin extract (GSPE) has been reported to modify glucose metabolism and β-cell functionality through its lipid-lowering effects in a diet-induced obesity model. The objective of the present study was to evaluate the effects of chronically administrated GSPE on the proteomic profile of pancreatic islets from Zucker fatty (ZF) rats. An isobaric tag for relative and absolute quantitation (iTRAQ) experiment was conducted and 31 proteins were found to be differentially expressed in ZF rats treated with GSPE compared to untreated ZF rats.