Proanthocyanidins Maintain Cardiac Ionic Homeostasis in Aldosterone-Induced Hypertension and Heart Failure.

Excess aldosterone promotes pathological remodeling of the heart and imbalance in cardiac ion homeostasis of sodium, potassium and calcium. Novel treatment with proanthocyanidins in aldosterone-treated rats has resulted in downregulation of cardiac SGK1, the main genomic aldosterone-induced intracellular mediator of ion handling. It therefore follows that proanthocyanidins could be modulating cardiac ion homeostasis in aldosterone-treated rats. Male Wistar rats received aldosterone (1 mg kg-1 day-1) +1% NaCl for three weeks. Half of the animals in each group were simultaneously treated with the proanthocyanidins-rich extract (80% w/w) (PRO80, 5 mg kg-1 day-1). PRO80 prevented cardiac hypertrophy and decreased calcium content. Expression of ion channels (ROMK, NHE1, NKA and NCX1) and calcium transient mediators (CAV1.2, pCaMKII and oxCaMKII) were reduced by PRO80 treatment in aldosterone-treated rats. To conclude, our data indicate that PRO80 may offer an alternative treatment to conventional MR-blockade in the prevention of aldosterone-induced cardiac pathology.

Evaluating the influence of temperature on proanthocyanidin biosynthesis in developing grape berries (Vitis vinifera L.).

The variability in grape (Vitis vinifera L.) proanthocyanidin content is largely attributable to viticultural and environmental conditions. However, the particular effect temperature has on proanthocyanidin biosynthesis is poorly understood. The aim of the present study was to ascertain the magnitude of the effect of temperature on proanthocyanidin biosynthesis in Cabernet Sauvignon grape berries cultured in vitro. In addition, the effects of temperature on global gene transcription were evaluated, and the microarray data were later validated by quantitative real-time PCR (qPCR). The grape berries used in this research were sampled 3-4 weeks after full bloom and cultured in vitro either under a low (20 °C) or high (30 °C) temperature treatment for 15 days (d) with sampling occurring every five days. The proanthocyanidin content was higher in the skin and seeds of grape berries cultured at a low temperature compared with a high temperature. However, overall proanthocyanidin composition between the treatments was not significantly affected. Microarray data revealed a total of 1298 genes with ≥ 3.5-fold expression differences under high temperature conditions. High temperature also inhibited the expression level of key genes involved in proanthocyanidin biosynthesis, anthocyanidin reductase (ANR) and leucoanthocyanidin reductase-1 (LAR-1) within the berry skin. However, the transcriptomic accumulation of transcription factors, such as VvMybPAs, VvMyb5a and VvMyb5b, was barely influenced during the peak expression of ANR and LAR-1. Thus, the present study revealed that temperature has a significant effect on proanthocyanidin biosynthesis in grape during berry development through enhancing the expression of key biosynthetic genes.

Proposed mechanisms of the effects of proanthocyanidins on glucose homeostasis.

Proanthocyanidins are a major group of flavonoids in the human diet, known for their strong antioxidant properties. Emerging evidence from clinical studies indicates a role of proanthocyanidins in modulating glucose homeostasis, and higher proanthocyanidin intake has been associated with reduced risk of diabetes. On the other hand, recent studies report limited bioavailability of proanthocyanidins. At relatively low concentrations in the systemic circulation, proanthocyanidins may act as cell-signaling molecules to modulate glucose homeostasis. For example, they affect hepatic glucose production via adenosine monophosphate-activated protein kinase and/or insulin-signaling pathways. There is also evidence for a direct role of proanthocyanidins in modulating several pancreatic ß-cell functions: prevention of oxidative stress, enhancement of insulin secretion, and promotion of ß-cell survival. Therefore, greater understanding of the potentially beneficial effects of proanthocyanidins on cell-signaling pathways implicated in glucose homeostasis is needed. In addition, further investigation to address the in vivo metabolism of proanthocyanidins and the comparative effectiveness of proanthocyanidin-derived metabolites is warranted. The dosage and the experimental model should be given special attention when results from mechanistic studies using proanthocyanidins are interpreted.

The Occurrence, Biosynthesis, and Molecular Structure of Proanthocyanidins and Their Effects on Legume Forage Protein Precipitation, Digestion and Absorption in the Ruminant Digestive Tract.

Forages grown in temperate regions, such as alfalfa (Medicago sativa L.) and white clover (Trefolium repens L.), typically have a high nutritional value when fed to ruminants. Their high protein content and degradation rate result, however, in poor utilization of protein from the forage resulting in excessive excretion of nitrogen into the environment by the animal. Proanthocyanindins (also known as condensed tannins) found in some forage legumes such as birdsfoot trefoil (Lotus corniculatus L.), bind to dietary protein and can improve protein utilization in the animal. This review will focus on (1) the occurrence of proanthocyanidins; (2) biosynthesis and structure of proanthocyanidins; (3) effects of proanthocyanidins on protein metabolism; (4) protein precipitating capacity of proanthocyanidins and their effects on true intestinal protein adsorption by ruminants; and (5) effect on animal health, animal performance and environmental emissions.

Novel oligomeric proanthocyanidin derivatives interact with membrane androgen sites and induce regression of hormone-independent prostate cancer.

Prostate cancer is the most common malignancy among men in Western societies, and current therapeutic approaches are evolving to manage growth, recurrence, and mortality neoplasia. Membrane androgen receptors (mARs) have been characterized in human prostate cancer, being preferentially expressed in tumor rather than benign gland areas. Furthermore, mAR agonists (protein-conjugated testosterone) decrease in vitro prostate cancer cell growth and induce apoptosis, whereas in vivo they regress growth of tumor xenografts alone or in combination with taxane drugs. In this respect, targeting mARs might be a novel therapeutic approach in prostate cancer. In our search for new small-molecule ligands of mAR, we report that flavanol dimers B1-B4 (oligomeric procyanidins) decrease in vitro growth of the androgen-sensitive (LnCaP) and androgen-resistant (DU145) human prostate cancer cell lines in the following order: B3 = B4 > B2 ≫ B1 (LnCaP) and B2 ≫ B3 = B4 ≫ B1 (DU145). Some of these analogs were previously shown to trigger signaling cascades similar to testosterone-bovine serum albumin (BSA) conjugate. Galloylation does not confer an additional advantage; however, oleylation increases the dimers' antiproliferative potency by a factor of 100. In addition, we report that B2, oleylated or not, displaces testosterone from mARs with an IC(50) value at the nanomolar range and induces DU145 tumor xenograft regression by 50% (testosterone-BSA 40%). In this respect, oleylated B2 is a potent small-molecule agonist of mAR and could be a novel therapeutic agent for advanced prostate cancer, especially when taking into account the absence of androgenic actions and (liver) toxicity.

Proanthocyanidins--a final frontier in flavonoid research?

Proanthocyanidins are oligomeric and polymeric end products of the flavonoid biosynthetic pathway. They are present in the fruits, bark, leaves and seeds of many plants, where they provide protection against predation. At the same time they give flavor and astringency to beverages such as wine, fruit juices and teas, and are increasingly recognized as having beneficial effects on human health. The presence of proanthocyanidins is also a major quality factor for forage crops. The past 2 years have seen important breakthroughs in our understanding of the biosynthesis of the building blocks of proanthocyanidins, the flavan-3-ols (+)-catechin and (-)-epicatechin. However, virtually nothing is known about the ways in which these units are assembled into the corresponding oligomers in vivo. Molecular genetic approaches are leading to an understanding of the regulatory genes that control proanthocyanidin biosynthesis, and this information, together with increased knowledge of the enzymes specific for the pathway, will facilitate the genetic engineering of plants for introduction of value-added nutraceutical and forage quality traits.

The role of bioactive tannins in the postpartum energy retention and productive performance of goats browsed in a natural rangeland.

The role of bioactive tannins in browse in the postpartum performance of goats grazed under natural range conditions was studied using 40 yearling Mubende goats (20+/-0.32 kg). In a completely randomized design, goats of one group (n = 20) received a daily drench of 50 g per goat of polyethylene glycol (PEG) of molecular weight 4000 given as a condensed tannin (CT) deactivator, and goats of the other group (n = 20) acted as the control (no PEG). Mean birth weights, live weight gains, abortion and twinning rates, litter size and tissue energy retention were measured. The PEG drench resulted in lower postpartum weight gains and tissue energy retention (p < 0.05). Postpartum weekly weight loss per doe was 0.65 kg in the PEG group and 0.46 kg in the control group, while tissue energy loss was 17.7 MJ per goat in the PEG group and 10.23 MJ per goat in the control group in the first 8 weeks. Net weight gain was observed in the control group at the 11 th week but was delayed in the PEG group (15th week). The PEG group had lower birth weights and higher kids mortalities (p <0.05). Selective feeding in the Ankole rangeland exposes goats to beneficial concentrations of dietary CT with apparent cumulative effects leading to improved postpartum performance of does and kids.