Proanthocyanidins from Vitis vinifera inhibit oxidative stress-induced vascular impairment in pulmonary arteries from diabetic rats

Background Vitis vinifera L. (grape seed extract) is a natural source of proanthocyanidins with antioxidant and free radical-scavenging activities. Hypothesis Grape seed extract supplementation may prevent vascular endothelium impairment associated with diabetes mellitus in rat pulmonary artery. Study design We evaluated endothelial function of rat pulmonary artery ex-vivo at the intermediate stage (4 weeks) of streptozotocin (STZ)-induced diabetes mellitus. We also evaluated the protective effect of grape seed extract administered daily, beginning the day after diabetes induction, or 15 days after diabetes induction, until the day of sacrifice. In addition, we compared the effect of grape seed extract supplementation with that of vitamin C. Methods Rats were made diabetic with streptozotocin (STZ, 65\ua0mg/kg i.v.). Thirty days later rats were sacrificed and pulmonary vessels reactivity and endothelial function compared to that of age-matched healthy animals. Results Concentration-response curves to ACh, NE, sodium nitroprusside (NO donor), but not to histamine and iloprost (prostacyclin analog), were significantly altered 4 weeks after STZ-injection. Antioxidant supplementation (3\ua0mg/kg/day) with either vitamin C or grape seed extract, starting the day after diabetes induction, significantly improved vasodilation to ACh and SNP. Norepinephrine-induced contractions were preserved by grape seed extract, but not vitamin C supplementation. Conversely, vitamin C but not grape seed extract showed beneficial effects contrasting the loss of body weight in diabetic animals. Abnormal vascular function was not reversed when antioxidant supplementations were postponed 15 days after the induction of diabetes. Conclusions This study provides scientific support for the therapeutic potential of an antioxidant therapy in endothelial impairment associated with diabetes. A daily supplementation of grape seed proanthocyanidins and/or vitamin C given at the earlier stage of disease may have a complementary role in the pharmacological therapy of diabetes and pulmonary vascular dysfunction

Profiling Vaccinium macrocarpon components and metabolites in human urine and the urine ex-vivo effect on Candida albicans adhesion and biofilm-formation

The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran\uae). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran\uae were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran\u2122 Phytosome\u2122, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-\u3b3-valerolactone was found effective thus confirming the ex-vivo results

Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals

<p>Abstract</p> <p>Background</p> <p>The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from <it>S. marianum</it>, is known to be an effective agent for liver protection and liver regeneration. The aim of this study was to investigate the protective actions of silymarin against hepatotoxicity caused by different combinations of anti-tuberculosis drugs.</p> <p>Methods</p> <p>Male Wistar albino rats weighing 250–300 g were used to form 6 study groups, each group consisting of 10 rats. Animals were treated with intra-peritoneal injection of isoniazid (50 mg/kg) and rifampicin (100 mg/kg); and intra-gastric administration of pyrazinamid (350 mg/kg) and silymarin (200 mg/kg). Hepatotoxicity was induced by a combination of drugs with INH+RIF and INH+RIF+PZA. Hepatoprotective effect of silymarin was investigated by co-administration of silymarin together with the drugs. Serum biochemical tests for liver functions and histopathological examination of livers were carried out to demonstrate the protection of liver against anti-tuberculosis drugs by silymarin.</p> <p>Results</p> <p>Treatment of rats with INH+RIF or INH+RIF+PZA induced hepatotoxicity as evidenced by biochemical measurements: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities and the levels of total bilirubin were elevated, and the levels of albumin and total protein were decreased in drugs-treated animals. Histopathological changes were also observed in livers of animals that received drugs. Simultaneous administration of silymarin significantly decreased the biochemical and histological changes induced by the drugs.</p> <p>Conclusion</p> <p>The active components of silymarin had protective effects against hepatotoxic actions of drugs used in the chemotherapy of tuberculosis in animal models. Since no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anti-tuberculosis medications.</p

Green tea catechins in chemoprevention of cancer: A molecular docking investigation into their interaction with glutathione S-transferase (GST P1-1)

The anti- and pro-oxidant effects of green tea catechins have been implicated in the alterations of cellular functions determining their chemoprotective and therapeutic potentials in toxicity and diseases. The glutathione S-transferases (GSTs; EC 2.5.1.18) family is a widely distributed phase-II detoxifying enzymes and the GST P1-1 isoenzyme has been shown to catalyze the conjugation of GSH with some alkylating anti-cancer agents, suggesting that over-expression of GST P1-1 would result in tumor cell resistance. Here we report the docking study of four green tea catechins and four alkylating anticancer drugs into the GST P1-1 model, as GSTs were found to be affected by tea catechins. The EGCG ligands exhibit higher docking potential with respect to the anticancer agents, with a ligand-receptor interaction pattern indicating an high conformational stability. Consequently, the competition mechanisms favourable for the green tea catechins could lead to enzyme(s) desensitisation with a reduction of the alkylating drugs metabolism. The results provide a useful theoretical contribution in understanding the biochemical mechanisms implicated in the chemotherapeutic use of green tea catechins in oxidative stress-related diseases

Nutraceutical properties of lupin seed proteins : a great potential still waiting for full exploitation

This review reports the experimentally demonstrated nutraceutical properties of lupin seed proteins. Lupin seed is a non-starchy, low-oil, protein- and fibre-rich legume seed, whose techno- and nutri-functional properties still await to be fully explored and exploited. This paper provides a comprehensive and up-dated survey on the bioactivities of lupin proteins and includes results on fibres, too. The described beneficial effects to human body span from plasma glucosedecreasing and hypertension-lowering activities to obesity, satiety and plasma lipid homeostasis controls. The review is intended to provide nutritionists, food scientists and technologists the state-of-art of the knowledge in the field of lupin seed protein oriented utilisation, as well as the nutri-functional reference sources for the best exploitation of this valuable, accessible, wealthy and healthy plant food