Rats were fed ag rape seed extract (GSE) containing ( þ )-catechin,( 2 )-epicatechin and dimers, trimers, tetramers and polymeric procyanidins. Liver, kidney, brain and gastrointestinal (GI) tract together with plasma, urine and faeces were collected over a24h period and their flavan-3-ol content was analysed by HPLC with tandem mass spectrometry and diode array detection. Small amounts of the GSE flavan-3-ols moved out of the stomach and into the duodenum/jejunum, and to ag reater extent the ileum 1h after ingestion, and into the caecum after 2h with relatively small amounts being detected in the colon after 3h.T he GI tract contained the parent GSE flavan-3-ols and procyanidins with only trace amounts of metabolites and there were no indications that proanthocyanidins were depolymerised in the GI tract releasing monomeric flavan-3-ols.Plasma contained exclusively catechin glucuronidesand methylated glucuronide metabolites which were also detected in the liver and kidneys. These metabolites were also present in urine together with sulphated metabolites and low amounts of the procyanidin dimers B 1 ,B 2 ,B 3 and B 4 as well as the trimer C 2 and an unknown GSE trimer. The amounts of ( þ )-catechin and ( 2 )-epicatechin metabolitesexcreted in urine relative to the quantity of the monomers ingested were 27 and 36 %, respectively, after 24 h. This is similar to the levels of urinary excretion reported to occur by other investigators after feeding ( 2 )-epicatechin to rats and provides further, albeit indirect, evidence that the procyanidinoligomers in the GSE were not depolymerised to monomers to any extent after ingestion. No convincing analytical data were obtained for the presence of flavan-3-ol metabolites in the brain.

No abstract

Epidemiological studies have reported a greater reduction in cardiovascular risk and metabolic disorders associated with diets rich in polyphenols. The antioxidant effects of polyphenols are attributed to the regulation of redox enzymes by reducing reactive oxygen species production from mitochondria, NADPH oxidases and uncoupled endothelial NO synthase in addition to also up-regulating multiple antioxidant enzymes. Although data supporting the effects of polyphenols in reducing oxidative stress are promising, several studies have suggested additional mechanisms in the health benefits of polyphenols. Polyphenols from red wine increase endothelial NO production leading to endothelium-dependent relaxation in conditions such as hypertension, stroke or the metabolic syndrome. Numerous molecules contained in fruits and vegetables can activate sirtuins to increase lifespan and silence metabolic and physiological disturbances associated with endothelial NO dysfunction. Although intracellular pathways involved in the endothelial effects of polyphenols are partially described, the molecular targets of these polyphenols are not completely elucidated. We review the novel aspects of polyphenols on several targets that could trigger the health benefits of polyphenols in conditions such as metabolic and cardiovascular disturbances.Key words: Polyphenols: Cardiovascular system: Nitric oxide: Endothelium: Free radicals: Antioxidants Polyphenols are found mainly in plant-derived foods and beverages, and provide the tastes and colour of plant foods while also participating in plant defensive responses against stress due to UV radiation, pathogens and physical damage. There are a number of excellent reviews dealing with their protective effect against cancers, cardiovascular, metabolic (1) and neurodegenerative diseases (2) . The structures of polyphenols vary from a simple phenol core to complex molecules with a high degree of polymerisation. This family can be divided into simple phenols, flavonoids and non-flavonoids such as stilbene (resveratrol), saponin, curcumin and tannins.

No abstract

[2-(14)C]quercetin-4'-glucoside (4 mg/kg body weight) was fed by gavage to rats housed in metabolic cages, and over an ensuing 72 h period, radiolabeled products in body tissues, plasma, feces, and urine were monitored by high-performance liquid chromatography with online radioactivity and MS2 detection. One and 6 h after ingestion, while in the small intestine, the flavonol glucoside was converted to glucuronide and methylated and sulfated derivatives of quercetin, but only trace amounts of these metabolites were excreted in urine. On entering the cecum and the colon, the flavonol metabolites declined as they were converted to phenolic acids, principally 3-hydroxyphenylacetic acid and 3,4-dihydroxyphenylacetic acid, by the colonic microflora. Feces contained mainly 3-hydroxyphenylacetic acid. Urine collected 0-12 and 0-24 h after ingestion contained radiolabeled hippuric acid and 3-hydroxyphenylacetic acid. 14C-Hippuric acid declined markedly in the 24-48 and 48-72 h urine samples, and there was a concomitant increase in labeled benzoic acid. There was minimal accumulation of radioactivity in plasma, despite a 69% recovery of label in urine over the 72 h period, and likewise, very little radioactivity was detected in body tissues out with the gastrointestinal tract. This is reflected in the fact that 72 h after ingestion 96% of the ingested radioactivity was recovered in feces, urine, and the cage washes, which comprise a mixture of urine and feces. The study reveals that as it passes through the gastrointestinal tract, almost all of the of [2-(14)C]quercetin-4'-glucoside is converted to phenolic acids, compounds not monitored in previous flavonol bioavailability studies with model animal systems, some of which have used exceedingly high doses of the aglycone quercetin (500 mg/kg body weight), which is not a normal dietary component.

To investigate the degree of absorption of flavan-3-ols in the small intestine, human subjects with an ileostomy ingested 200 mg of Polyphenon E, a green tea extract, after which ileal fluid and urine, collected over a 24-h period, were analyzed by high-performance liquid chromatography with photodiode array and mass spectrometric detection. The data obtained indicated that although approximately 40% of flavan-3-ol intake is recovered in ileal fluid, substantial quantities are absorbed in the small intestine. Moreover, 14 urinary metabolites, comprising sulfates, glucuronide, and methylated derivatives, were identified and quantified. All were metabolites of (epi)catechin or (epi)gallocatechin, representing 47 +/- 2% and 26 +/- 9%, respectively, of the ingested parent compound. These high recoveries indicate that these flavan-3-ols absorbed in the small intestine are much more bioavailable than most dietary flavonoids. No 3-O-galloylated flavan-3-ols or their metabolites were detected in urine. The absence of urinary flavan-3-ol metabolites after ingestion of 200 mg of (-)-epigallocatechin gallate indicates that there is no removal of the 3-O-galloyl group in vivo, and hence, this does not account for the high urinary recovery of (epi)gallocatechin metabolites after ingestion of Polyphenon E. Increasing the intake of Polyphenon E, by feeding doses of 200, 500, and 1500 mg, led to increased urinary excretion of (epi)catechin metabolites but not metabolites of (epi)gallocatechin. Coingestion of 200 mg of Polyphenon E with bread, cheese, or glucose did not significantly modify the absorption, metabolism, and excretion of flavan-3-ols. It does not necessarily follow, however, that the same would occur when flavan-3-ols are ingested with more complex food matrices.

Cannabis has potential therapeutic use but tetrahydrocannabinol (THC), its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities V max (complexes I, III, and IV activities), V succ (complexes II, III, and IV activities), V tmpd (complex IV activity), together with mitochondrial coupling (V max/V 0), were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2) production, measured with Amplex Red. THC significantly decreased V max (−71%; P < 0.0001), V succ (−65%; P < 0.0001), and V tmpd (−3.5%; P < 0.001). Mitochondrial coupling (V max/V 0) was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P < 0.001). Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P < 0.05) and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P < 0.001). Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient's vulnerability to stroke.

These findings indicate that endothelial-derived MPs from ACS patients induce premature endothelial senescence under atheroprone low shear stress and thrombogenicity through angiotensin II-induced redox-sensitive activation of mitogen-activated protein kinases and phosphoinositide 3-kinase/Akt. They further suggest that targeting endothelial-derived MP shedding and their bioactivity may be a promising therapeutic strategy to limit the development of an endothelial dysfunction post-ACS.