Search

Introduction Asarum sieboldii (named Hua Xixin in Chinese) belongs to the family Aristolochiaceae and is a renowned traditional Chinese medicinal (TCM) herb that grows primarily in the Qinling-Bashan mountain region [...], Asarum sieboldii, a well-known traditional Chinese medicinal herb, is used for curing inflammation and ache. It contains both the bioactive ingredient asarinin and the toxic compound aristolochic acid. To address further breeding demand, genes involved in the biosynthetic pathways of asarinin and aristolochic acid should be explored. Therefore, the full-length transcriptome of A sieboldii was sequenced using PacBio Iso-Seq to determine the candidate transcripts that encode the biosynthetic enzymes of asarinin and aristolochic acid. In this study, 63 023 full-length transcripts were generated with an average length of 1371 bp from roots, stems, and leaves, of which 49 593 transcripts (78.69%) were annotated against public databases. Furthermore, 555 alternative splicing (AS) events, 10 869 long noncoding RNAs (lncRNAs) as well as their 11 291 target genes, and 17 909 simple sequence repeats (SSRs) were identified. The data also revealed 97 candidate transcripts related to asarinin metabolism, of which six novel genes that encoded enzymes involved in asarinin biosynthesis were initially reported. In addition, 56 transcripts related to aristolochic acid biosynthesis were also identified, including CYP81B. In summary, these transcriptome data provide a useful resource to study gene function and genetic engineering in A sieboldii. Key words: PacBio sequencing, Asarum sieboldii, asarinin, aristolochic acid, CYP. L'Asarum sieboldii est une plante medicinale bien connue en medicine traditionnelle chinoise. Elle est employee pour guerir l'inflammation et les douleurs. Elle contient a la fois un compose bioactif, l'asarinine, et un compose toxique, l acide aristolochique. Pour mieux repondre aux besoins des selectionneurs, il est important d'identifier les genes impliques dans les voies de synthese de l'asarinine et de l'acide aristolochique. Les auteurs ont sequence le transcriptome de pleine longueur de l'A sieboldii al'aide d'une approche Iso-Seq de PacBio pour identifier des transcrits candidats qui codent pour les enzymes synthetiques de l'asarinine et de l'acide aristolochique. Dans ce travail, 63 023 transcrits de pleine longueur ont ete generes a partir de racines, de tiges ou de feuilles et la longueur moyenne de ces transcrits etait de 1371 pb. De ce nombre, 49 593 (78,69 %) ont ete annotes en les comparant avec des bases de donnees publiques. De plus, 555 produits d'un epissage alternatif, 10 869 lncRNA ainsi que les 11291 genes qu'ils ciblent, et 17 909 SSR ont ete identifies. Ces donnees ont permis d'identifier 97 transcrits candidats impliques dans le metabolisme de l'asarinine de meme que 56 transcrits impliques dans la synthese de l'acide aristolochique dont CYP81B. En somme, ce transcriptome fournit une ressource utile pour l'etude de la fonction des genes et l'ingenierie genetique chez l'A. sieboldii. [Traduit par la Redaction] Mots-cles: sequencage PacBio, Asarum sieboldii, asarinine, acide aristolochique, CYP.

Pearl millet and other minor cereal production is marginalized in the Sahara of Algeria (Tidikelt and Hoggar regions). Their productions in these areas depend on traditional harvesting and processing. Pearl millet seeds are used as animal feed and rarely for human consumption. This work was to assess the starch digestion of pearl millet cultivated in the arid areas of Algeria. The seeds from this cereal could provide broad potential benefits to human health. However, their digestion properties have not been reported. Therefore, in this study, the in-vitro starch digestibility of pearl millet flour and the effect of processing on the expected glycemic index (eGI) were investigated. Grains from six pearl millet samples were chosen from two regions: Tidikelt and Hoggar. Five flours were prepared by dry milling (MF) and different treatments after dry milling such as extraction of phenolic compounds (MF-PP), lipid extraction (MF-L), protein hydrolysate extraction (MF-P) or lipid plus protein hydrolysate extraction (MF-L-P). The flours were then subjected to digestion, and the effects of grain treatments on the in vitro starch digestion were investigated. For all pearl millet samples, the kinetics of in vitro starch digestion displayed first-order model as substrates were digested to different extents; k (kinetic constant), C[infinity] (percentage of starch hydrolyzed at infinite time), HI (hydrolysis index) and eGI (expected glycemic index) of the samples were also calculated. Significant increases in C[infinity], HI and eGI (P69), with values ranging between 77.50 and 121.44. This study confirmed that some of the processed pearl millet seed flours have acceptable nutritional values suitable for human health and nutrition due to the low glycemic index values. Key words: Pearl millet, Grain processing, Starch digestion, First-order model, Glycemic index, INTRODUCTION Millets are important crops in semi-arid and tropical regions of the world [1]. The most important species are pearl millet, finger millet, proso millet, and foxtail millet. Pearl millet [...]

Vitis amurensis (Vitaceae) has been reported to have anti-oxidant and anti-inflammatory activities. The present study investigated a methanol extract from the leaf and stem of V. amurensis for neuroprotective effects [...]

Low iron absorption from common beans might contribute to iron deficiency in countries where beans are a staple food. High levels of phytic acid (PA) and polyphenols (PP) inhibit iron absorption; however, the effect of bean PP on iron absorption in humans has not been demonstrated and, with respect to variety selection, the relative importance of PP and PA is unclear. To evaluate the influence of bean PP relative to PA on iron absorption in humans, 6 stable iron isotope absorption studies were conducted in women (16 or 17 per study). Bean PP (20, 50, and 200 mg) were added in studies 1-3 as red bean hulls to a bread meal. Studies 4- 6 investigated the influence on iron absorption of PP removal and dephytinization of whole red bean porridge and PP removal from dephytinized porridge. Iron absorption was lowered by 14% with 50 mg PP (P < 0.05) and by 45% with 200 mg PP (P < 0.001). The mean iron absorption from whole bean porridge was 2.5%. PP and PA removal increased absorption 2.6-fold (P < 0.001) and removal of PP from dephytinized porridge doubled absorption (P < 0.001). Between-study comparisons indicated that dephytinization did not increase iron absorption in the presence of PP, but in their absence, absorption increased 3.4-fold (P < 0.001). These data suggest that in countries where beans are a staple food, PP and PA concentrations should be considered when selecting bean varieties for human consumption. Lowering only one inhibitor will have a modest influence on iron absorption. J. Nutr. 140:1977- 1982, 2010. doi: 10.3945/jn.110.125369.

A single-blind, placebo-controlled, and randomized trial study was carried out with 16 healthy volunteers (7 men and 5 women). The test group ingested an encapsulated almond skin phenolic extract (884 mg of total polyphenols/dose) containing flavan-3-ols, flavonols, and flavanones, whereas the placebo group ingested microcrystalline cellulose. Our aim in this study was to determine changes in the urinary excretion of conjugated and microbial-derived phenolic metabolites before (-2 to 0 h) and after (0-2, 2-6, 6-10, and 10-24 h) intake of the almond polyphenols compared with the placebo group. For the test group, maximum urinary excretion of (epi)catechin and naringenin conjugates derived from phase II metabolism was attained at 2-6 h after consumption of the almond skin extract and excretions differed from the placebo group during this time period (P [less than or equal to] 0.0001). However, excretion of conjugated metabolites of isorhamnetin was highest at 10-24 h and did not differ from the placebo group during this time (P > 0.05). Hydroxyphenylvalerolactones reached maximum urinary levels at 6-10 h after consumption of almond polyphenols, and excretion differed from the placebo group during this time period (P [less than or equal to] 0.0004). For the test group, excretions of phenolic acids (hydroxyphenylpropionic, hydroxyphenylacetic, hydroxybenzoic, and hydroxycinnamic acids) did not differ from the placebo group at any time period of urine collection (P > 0.05). The findings presented in this work provide evidence concerning the bioavailability of almond skin polyphenols considering the effects of both phase II and microbial metabolism. doi: 10.3945/jn.110.124065.

This study shows that exposure to low concentrations of the polyphenol tannic acid (TA) induces potent life-prolonging properties in Caenorhabditis elegans. In addition, enhanced thermal stress resistance, reduced growth, and slightly increased oxidative stress resistance were observed, although reproductive capacities and pharyngeal pumping rate were not modulated. Exploiting a suite of 14 mutant strains revealed that the mitogen-activated protein kinase kinase SEK-1 (SAPK/ERK kinase) is a key player involved in TA-mediated longevity. It is conceivable that TA mimics pathogen action and therefore activates the SEK-1-mediated pathogen resistance pathway. This pathway is thought to inhibit potential detrimental effects of TA and may also be involved in the longevity process. The observed dose response suggests the presence of a hormesis effect, and the growth impairment is in agreement with the 'Disposable Soma Theory.' This report underlines the uniqueness of TA-mediated longevity and facilitates a first glimpse into its complex mode of action. doi: 10.1093/gerona/glq051

Berries are a good source of polyphenols, especially anthocyanins, micronutrients, and fiber. In epidemiological and clinical studies, these constituents have been associated with improved cardiovascular risk profiles. Human intervention studies using chokeberries, cranberries, blueberries, and strawberries (either fresh, or as juice, or freeze-dried), or purified anthocyanin extracts have demonstrated significant improvements in LDL oxidation, lipid peroxidation, total plasma antioxidant capacity, dyslipidemia, and glucose metabolism. Benefits were seen in healthy subjects and in those with existing metabofic risk factors. Underlying mechanisms for these beneficial effects are believed to include upregulation of endothelial nitric oxide synthase, decreased activities of carbohydrate digestive enzymes, decreased oxidative stress, and inhibition of inflammatory gene expression and foam cell formation. Though limited, these data support the recommendation of berries as an essential fruit group in a heart-healthy diet. Key words: anthocyanins, berries, inflammation, lipid peroxidation, nitric oxide doi: 10.1111/j.1753-4887.2010.00273.x

Author(s): Sumanto Haldar [sup.1] , Siok Ching Chia [sup.1] , Christiani Jeyakumar Henry [sup.1] [sup.2] Author Affiliations: (1) Clinical Nutrition Research Centre (CNRC), Singapore Institute for Clinical Sciences (SICS), Agency [...], Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis. Evidence is emerging that dietary bioactive phytochemicals such as polyphenols can increase GLP-1 concentration in vivo. Spices are rich in polyphenols and have oro-sensory properties, both of which can increase GLP-1 secretion. We therefore investigated the effects of mixed spices intake on postprandial GLP-1 concentration. Using a randomised, controlled, dose-response crossover trial in 20 young, healthy, Chinese men, volunteers were served white rice with 3 doses of curry made with mixed spices and vegetables. These test meals were isocaloric and macronutrient matched. Plasma total GLP-1 concentrations were measured before (baseline) and for up to 3 h after the consumption of test meals. We found a significant dose dependent increase in total AUC of plasma GLP-1 concentrations, adjusted for baseline, with increasing mixed spice doses [adjusted mean ([plus or minus]SEM) of 10568.3 [plus or minus] 1267.9, 12391.8 [plus or minus] 1333.94, and 13905.1 [plus or minus] 1267.6 pg ml.sup.-1.min for Dose 0 Control, Dose 1 Curry and Dose 2 Curry respectively (p = 0.019)]. Consumption of polyphenol rich mixed spices and vegetables can therefore increase in vivo GLP-1 concentration.

Tristetraprolin (TTP/zinc finger protein 36) family proteins have antiinflammatory effects by destabilizing proinflammatory mRNA. TTP expression is reduced in fats of obese people with metabolic syndrome and brains of suicide victims and is induced by insulin and cinnamon polyphenol extract (CPE) in adipocytes, by lipopolysaccharide (LPS) in macrophages, and by green tea polyphenol extract in rats. CPE was reported to improve immune function against microorganisms, but the mechanism is unknown. This study tested the hypothesis that CPE regulates immune function involving genes encoding TTP, proinflammatory cytokines, and glucose transporter (GLUT) families and compared the effects of CPE to those of insulin and LPS in mouse RAW264.7 macrophages. CPE increased TTP mRNAand protein levels, but its effects were less than LPS. CPE (100 mg/L, 0.5-4 h) increased TTP and tumor necrosis factor (TNF) mRNA levels by up to 2- and 6-fold that of the control, respectively, and the base level of TTP was 6-fold that of TNF. LPS (0.1 mg/L, 4 h) increased TTP, TNF, granulocyte-macrophage colony-stimulating factor, cyclooxgenase-2, and interleukin 6 mRNA levels by 39-1868 fold. CPE and LPS increased GLUT1 expression (the major GLUT form in macrophages) to 3- and 2-fold that of the control, respectively. Insulin (100 nmol/L, 0.5-4 h) did not exhibit major effects on the expression of these genes. CPE increased FIP expression more rapidly than those of proinflammatory cytokines and the net increases of TTP mRNA levels were larger than those of proinflammatory cytokines. These results suggest that CPE can affect immune responses by regulating anti- and proinflammatory and GLUT gene expression.

Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, may augment metabolic and vascular actions of insulin. Therefore, we investigated effects of EGCG treatment to simultaneously improve cardiovascular and metabolic function in spontaneously hypertensive rats (SHR; model of metabolic syndrome with hypertension, insulin resistance, and overweight). In acute studies, EGCG (1-100 [micro]M) elicited dose-dependent vasodilation in mesenteric vascular beds (MVB) isolated from SHR ex vivo that was inhibitable by [N.sup.[omega]]-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase antagonist) or wortmannin [phosphatidylinositol (PI) 3-kinase inhibitor]. In chronic studies, 9-wk-old SHR were treated by gavage for 3 wk with EGCG (200 mg x [kg.sup.-1] x [day.sup.-1]), enalapril (30 mg x [kg.sup.-1] x [day.sup.-1]), or vehicle. A separate group of SHR receiving L-NAME (80 mg/l in drinking water) was treated for 3 wk with either EGCG or vehicle. Vasodilator actions of insulin were significantly improved in MVB from EGCG- or enalapril-treated SHR (when compared with vehicle-treated SHR). Both EGCG and enalapril therapy significantly lowered systolic blood pressure (SBP) in SHR. EGCG therapy of SHR significantly reduced infarct size and improved cardiac function in Langendorff-perfused hearts exposed to ischemia-reperfusion (I/R) injury. In SHR given L-NAME, beneficial effects of EGCG on SBP and I/R were not observed. Both enalapril and EGCG treatment of SHR improved insulin sensitivity and raised plasma adiponectin levels. We conclude that acute actions of EGCG to stimulate production of nitric oxide from endothelium using PI 3-kinase-dependent pathways may explain, in part, beneficial effects of EGCG therapy to simultaneously improve metabolic and cardiovascular pathophysiology in SHR. These findings may be relevant to understanding potential benefits of green tea consumption in patients with the metabolic syndrome. epigallocatechin gallate; insulin resistance; endothelial dysfunction; nitric oxide; metabolic syndrome; spontaneously hypertensive rats; ischemia-reperfusion doi: 10.1152/ajpendo.00698.2006

The potential of natural dietary polyphenols in the treatment of vascular diseases originating from veins has been suggested in the literature. However, the mechanisms involved to explain the effects of polyphenols are not yet elucidated. Therefore, the aim of this study was to investigate the mechanisms by which polyphenols from red wine (Provinols) modulated contraction in human veins. We took advantage of a human model previously reported as a new tool for pharmacological research, using tissue-engineered techniques allowing the production of vascular media based exclusively on human smooth muscle cells. Thus human tissue-engineered vascular media (TEVM) were produced with cells originating from umbilical cord vein. TEVM were treated with either vehicle or Provinols. Results showed that treatment of TEVM with Provinols significantly potentiated the contractile responses induced by histamine and bradykinin. The potentiating effect of Provinols was not associated with an enhancement of histamine-induced increase in cytosolic calcium; rather, it implied the presence of a C[a.sup.2+]-independent signaling pathway. Pharmacological studies indicated that action of Provinols took place at the level of phospholipase [A.sub.2]-Rho-kinase pathway and was associated with an enhancement of myosin light chain kinase activity. These results, obtained using the human TEVM, bring new insights to explain the regulation of venous contraction by polyphenols. tissue engineering; veins; smooth muscle

Among the numerous polyphenols isolated from green tea, the catechin EGCG predominates and is the target of anticancer research. But studies suggest that EGCG and other catechins are poorly absorbed and undergo substantial bio-transformation to species that include glucuronides, sulfates, and methylated compounds. Numerous studies relate the antioxidant properties of the catechins with anticancer effects, but recent research proposes other mechanisms of action, including those involving methyl transfers that are subject to allelic variability in the enzyme catechol O-methyl transferase. However, preclinical research is promising and EGCG appears to be ready for further study in phase II and III trials. Key words: green tea, polyphenols, cancer chemoprevention, catechin doi: 10.1301/nr.2004.may.204-211

Polyphenolic components of green tea, such as epigallocatechin-3-gallate (EGCG), have potent anti-inflammatory properties. We previously showed that EGCG inhibits tumor necrosis factor-[alpha] (TNF-[alpha])-mediated activation of the nuclear factor-[kappa]B (NF-[kappa]B) pathway, partly through inhibition of I[kappa]B kinase (IKK). The NF-[kappa]B pathway may also be activated in response to interleukin-1[beta] (IL-1[beta]) stimulation through a distinct signal transduction pathway. We therefore hypothesized that EGCG inhibits IL-1[beta]-mediated activation of the NF-[kappa]B pathway. Because the gene expression of interleukin-8 (IL-8), the major human neutrophil chemoattractant, is dependent on activation of NF-[kappa]B, IL-8 gene expression in human lung epithelial (A549) cells treated with human IL-1[beta] was used as a model of IL-1[beta] signal transduction. The EGCG markedly inhibited IL-1[beta]-mediated IL-1[beta] receptor-associated kinase (IRAK) degradation and the signaling events downstream from IRAK degradation: IKK activation, I[kappa]B[alpha] degradation, and NF-[kappa]B activation. In addition, EGCG inhibited phosphorylation of the p65 subunit of NF-[kappa]B. The functional consequence of this inhibition was evident by inhibition of IL-8 gene expression. Therefore, the green tea polyphenol EGCG is a potent inhibitor of IL-1[beta] signal transduction in vitro. The proximal mechanisms of this effect involve inhibition of IRAK-dependent signaling and phosphorylation of p65. KEY WORDS: * transcription factors * inflammation * signal transduction * chemokines * polyphenols

The melanogenic marine bacterium Marinomonas mediterranea synthesizes R-bodies as revealed by transmission electron microscopy. These structures were previously described in some obligate symbionts of paramecia and some free-living bacteria, none of which was isolated from sea water. In other micro-organisms, the synthesis of R-bodies has been related to extrachromosomal elements. Accordingly, M. mediterranea induction by mitomycin C or UV radiation resulted in the production of defective phages resembling bacteriocins, indicating that it is a lysogenic bacterium. Two mitomycin-C-resistant strains defective in prophage replication have been isolated. These mutants, and the previously obtained strains ngC1, T102 and T103, the latter mutated in the ppoS gene encoding a sensor histidine kinase, are affected not only in phage replication but also in polyphenol oxidase activities and melanin synthesis, suggesting a relationship between the control of all these processes.

Female ovariectomized guinea pigs, a model for menopausal women, were fed either a control diet or a diet containing 10 g/100 g of a lyophilized grape preparation for 12 wk. The macronutrient composition of the grape preparation was: simple carbohydrates, 90 g/100 g; protein, 4 g/100 g; and dietary fiber, 6 g/100 g. Control and grape diets had the same composition except for the percentage of macronutrients provided by the grape preparation. Polyphenols were present in the grape preparation at 0.58 g/100 g and included flavans, anthocyanins, quercetin, myricetin, kaempferol and resveratrol. Dietary cholesterol was 0.33 g/100 g to raise plasma cholesterol concentrations and ensure the development of atherosclerosis. Plasma LDL cholesterol concentrations did not differ between groups, whereas plasma triglycerides and VLDL cholesterol were 39 and 50% lower, respectively in guinea pigs fed the grape diet compared with controls (P < 0.05). Significant modifications in LDL particles included 58 and 30% lower triglycerides and phospholipids, respectively (P < 0.0001). Hepatic acyl CoA:cholesteryl acyltransferase activity was 27% lower (P < 0.05) in the grape diet-fed group compared with controls. In addition, concentrations of cholesterol in the aorta were 33% lower (P < 0.05) in guinea pigs fed the grape diet. These results suggest that grape intake in ovariectomized guinea pigs alters hepatic cholesterol metabolism, which may affect VLDL secretion rates and result in less accumulation of cholesterol in the aorta. KEY WORDS: * grape polyphenols, atherosclerosis * plasma triglycerides * guinea pigs

Epidemiologic studies suggest that the consumption of red wine may lower the risk of cardiovascular disease. The cardioprotective effect of red wine has been attributed to the polyphenols present in red wine, particularly resveratrol (a stilbene, with estrogen-like activity), and the flavonoids, catechin, epicatechin, quercetin and phenolic acids such as gallic acid. At present, very little is known about the mechanisms by which red wine phenolic compounds benefit the cardiovascular system. Therefore, the aim of this study was to elucidate whether red wine polyphenolics reduce lipoprotein production and clearance by the liver. Cultured HepG2 cells were incubated in the presence of dealcoholized red wine, alcohol-containing red wine and atorvastatin for 24 h. The apolipoprotien B100 (apoB100) protein (marker of hepatic lipoproteins) was quantified on Western blots with an anti-apoB100 antibody and the enhanced chemiluminescence detection system. Apolipoprotein B100 levels in the cells and that secreted into the media were significantly reduced by 50% in liver cells incubated with alcohol-stripped red wine compared with control cells. This effect of dealcoholized red wine on apoB100 production in HepG2 cells was similar to the effect of atorvastatin. Apo B100 production was significantly attenuated by 30% in cells incubated with alcoholized red wine, suggesting that the alcohol was masking the effect of red wine polyphenolics. Apo B100 production was significantly attenuated by 45% with the polyphenolic compounds resveratrol and quercertin. In addition, dealcoholized and alcoholized red wine and atorvastatin significantly increased 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA and LDL receptor binding activity relative to controls. Dealcoholized red wine also increased LDL receptor gene expression. Collectively, this study suggests that red wine polyphenolics regulate major pathways involved in lipoprotein metabolism. KEY WORDS: * apoB100 * red wine polyphenolics * cholesterol * LDL receptor * lipoproteins

The health effects of dietary polyphenols might be explained by both intact compounds and their metabolites formed either in the tissues or in the colon by the microflora. The quantitative importance and biological activities of the microbial metabolites have seldom been examined in vivo. We measured the microbial metabolites formed in four groups of rats (n = 8) fed for 8 d a diet supplemented with 0.12 g/100 g catechin, 0.25 or 0.50 g/100 g red wine powder containing proanthocyanidins, phenolic acids, flavanols, anthocyanins and flavonols or an unsupplemented diet. Fourteen aromatic acid metabolites were assayed in urine collected for 24 h by an HPLC-electrospray ionization (ESI)-mass spectrometry (MS)-MS method. The three main metabolites formed from the catechin diet were 3-hydroxyphenylpropionic acid, 3-hydroxybenzoic acid and 3-hydroxyhippuric acid. Their total urinary excretion accounted for 4.7 g/100 g of the catechin ingested and that of intact catechins for 45.3 g/100 g. For wine polyphenols, the same microbial metabolites as observed for the catechin diet were identified in urine along with hippuric, p-coumaric, vanillic, 4-hydroxybenzoic and 3-hydroxyphenylacetic acids. All together, these aromatic acids accounted for 9.2 g/100 g of the total wine polyphenols ingested and intact catechins for only 1.2 g/100 g. The higher excretion of aromatic acids by rats fed wine polyphenols is likely due to their poor absorption in the proximal part of the gut. Some of the microbial metabolites still bear a reducing phenolic group and should also prevent oxidative stress in inner tissues. More attention should be given in the future to these microbial metabolites and their biological properties to help explain the health effects of polyphenols that are not easily absorbed through the gut barrier. KEY WORDS: * polyphenols * catechin * wine * gut microflora * microbial metabolites * rats

Red wine is a rich source of polyphenols, which exhibit a number of biological effects in different in vitro and in vivo systems. The bioavailability of polyphenols is poor and the plasma concentrations of major red wine polyphenols are usually low after consumption of dietary relevant amounts of red wine. In contrast to most organ systems, the gastrointestinal tract (particularly the epithelial cells of this organ system) is exposed to high concentrations of polyphenols. Here, we show that the total polyphenol pool isolated from a red wine (varity Lemberger, vintage 1998) at micromolar concentrations inhibited the proliferation of transformed colon epithelial cells HT 29 clone 19A induced by epidermal growth factor (EGF). Inhibition of proliferation was also associated with modulation of activation of mitogen-activated protein kinases (MAPK). Stress activated c-Jun N-terminal kinases 1/2 (JNK) and p38 MAPK were significantly activated by red wine polyphenols (6 mmol/L). Maximum phosphorylation of both MAPK was observed after a 1-h treatment with red wine polyphenols. In contrast, activation of extracellular signal regulated kinase (ERK) 1/2 by EGF (1 nmol/L) was significantly inhibited by red wine polyphenols (6 mmol/L). This signaling pattern, activation of JNK 1/2 and p38 MAPK and inhibition of ERK 1/2, is typical for antiproliferative compounds, indicating that red wine polyphenols may inhibit the proliferation of colon carcinoma cells by modulating MAPK intracellular signal transduction pathways. KEY WORDS: * red wine polyphenols * intracellular signaling * mitogen-activated protein kinases

The in vitro capacities of individual polyphenols in red wine to inhibit the cell-mediated oxidation of lipoproteins and their effects on cell viability were determined. LDL and HDL were incubated with J774.A1 macrophages and 2 and 4[micro]mol/L copper, respectively, in the absence and presence of polyphenols in ethanol at concentrations found in red wine. A mixture of polyphenols in amounts found in red wine equivalent to 0.2 g/L ethanol and 0.05 g/L ethanol inhibited thiobarbituric acid-reactive substance production from LDL by 91.7 and 45.9%, respectively, compared with ethanol controls (P < 0.01). HDL oxidation was inhibited 85 and 82.4% by the polyphenols at 0.2 and 0.05 g/L ethanol (P < 0.01). The effects of the polyphenol mixture on LDL oxidation were confirmed by measuring production of conjugated dienes and lipid peroxides, and trinitrobenzene sulfonic acid reactivity. Catechin at the concentration found in red wine (1.32 [micro] mol/L) at an ethanol concentration equivalent to 0.2 g/L inhibited LDL oxidation by 83.2%, while epicatechin (0.56 [micro]mol/L) and gallic acid (1.02 [micro]mol/L) inhibited by 60.6 and 26.9%, respectively (P < 0.05). At 1 [micro]mol/L, LDL oxidation was inhibited by epicatechin, catechin and quercetin by 86.2, 79.9 and 69.4%, respectively (P < 0.05). Incubation of macrophages with ethanol alone and with polyphenols in ethanol did not affect cell viability. Our results indicate that catechin and epicatechin are the major contributors to the antioxidant activity of red wine. KEY WORDS: * wine * polyphenol * lipoprotein oxidation * macrophage * cell viability