Dietary Catechins Research Articles

J-shaped association of dietary catechins intake with the prevalence of osteoarthritis and moderating effect of physical activity: an American population-based cohort study.

Catechins are a class of natural compounds with a variety of health benefits, The relationship between catechins and the prevalence of osteoarthritis (OA) is unknown. This study investigated the associations between daily intake of catechins and the prevalence of OA among American adults and assessed the moderating effect of physical activity (PA). This study included 10,039 participants from the National Health and Nutrition Examination Survey (2007-2010,2017-2018). The logistic regression, weighted quantile sum (WQS) regression, and restricted cubic spline (RCS) regression models were conducted to explore the associations between daily intake of catechins and the prevalence of OA. Moreover, interaction tests were performed to assess the moderating effect of PA. After multivariable adjustment, the weighted multivariable logistic regression and RCS regression analyses revealed significant J-shaped non-linear correlations between intakes of epigallocatechin and epigallocatechin 3-gallate had significant associations with the prevalence of OA among in U.S. adults. WQS regression analysis showed that excessive epigallocatechin intake was the most significant risk factor for OA among all subtypes of catechins. In the interaction assay, PA showed a significant moderating effect in the relationship between epigallocatechin intake and OA prevalence. The intake of gallocatechin and gallocatechin 3-gallate had a significant negative correlation with the prevalence of OA and the dose-response relationship was J-shaped.PA below 150 MET-min/week and the threshold intakes of 32.70mg/d for epigallocatechin and 76.24mg/d for epigallocatechin 3-gallate might be the targets for interventions to reduce the risk of developing OA.

Role of flavonoids in digestive tract cancer prevention - a review article

Introduction: Flavonoids are bioactive chemical compounds crucial for the functioning of plant organisms. Recently, they have been intensively studied in search of their potential application in medicine. One of the most popular fields in that regard is oncology. Digestive tract cancers are still a challenge for contemporary medicine. Our diet seems to have a direct impact on the etiology of colorectal, gastric, and esophageal cancers. The relationship between the consumption of flavonoids, their specific fractions, and digestive tract cancer morbidity is nowadays frequently investigated.Purpose: This review article aims to discuss the most recent scientific reports and summarize the current state of knowledge, considering the role of flavonoids in digestive tract cancer prevention.Materials and methods: Our work is based on articles accessed through medical information databases (Google Scholar, PubMed, CrossRef), various scientific books, and official NFZ and WHO-certified sites.Results: Total flavonoid intake lowers gastric and esophageal cancer morbidity. A high amount of dietary catechins prevents the growth of gastric and colorectal cancer. Increased consumption of anthocyanidins, flavones, and flavanones decreases esophageal cancer morbidity. Isoflavones, procyanidines, anthocyanidins, flaonols, and flavones severely decrease the chance of developing colorectal cancer.Conclusions: Flavonoids can play an important role in digestive tract cancer prevention. They suppress the growth of colorectal, gastric, and esophageal cancers. Nevertheless, new, high-quality studies are needed in order to compile adequate procedures and bring new, potential drugs to the market.

Effects of Dietary Catechin Uncaria gambir Extract on Growth Performance, Carcass Characteristics, Plasma Lipids, Antioxidant Activity and Nutrient Digestibility in Broiler Chickens

This study aimed to determine the effect of adding catechin gambir extract (Uncaria gambir Roxb) (CGE) on growth performance, carcass characteristics, blood plasma constituents, antioxidant activity, and nutrient digestibility in broiler chickens. 160 chicks were allocated to receive four treatment diets adding CGE was 0, 0.1, 0.2, and 0.3g/kg in basal diets with four replications. Bodyweight and feed intake were recorded to calculate growth performance. Digestibility measurements were carried out at the age of 31-40 days, and at 40 days, blood samples were taken to determine the total protein levels of cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL), and Malondialdehyde (MDA). Then these chickens are slaughtered to determine the percentage of viscera and muscles. Adding CGE to basal diets linearly (P<0.05) increased body weight gain and improved the feed conversion ratio of broiler grower, finisher, and the overall age of 1-40 days. The effect of GCE on carcass characteristics significantly (P<0.05) increased the percentage of thigh and drumstick and decreased abdominal fat. CGE linearly reduced total cholesterol and LDL while increased HDL and total protein in blood plasma. The MDA concentration linearly decreased in serum and broiler meat aged 40 days. In addition, CGE increased (P<0.05) the digestibility of crude protein and decreased fat digestibility in the diet. Adding 0.3g/kg CGE to the basal diet can be a feed additive to produce better performance and broiler meat.

The Donor-Dependent and Colon-Region-Dependent Metabolism of (+)-Catechin by Colonic Microbiota in the Simulator of the Human Intestinal Microbial Ecosystem.

The intestinal absorption of dietary catechins is quite low, resulting in most of them being metabolized by gut microbiota in the colon. It has been hypothesized that microbiota-derived metabolites may be partly responsible for the association between catechin consumption and beneficial cardiometabolic effects. Given the profound differences in gut microbiota composition and microbial load between individuals and across different colon regions, this study examined how microbial (+)-catechin metabolite profiles differ between colon regions and individuals. Batch exploration of the interindividual variability in (+)-catechin microbial metabolism resulted in a stratification based on metabolic efficiency: from the 12 tested donor microbiota, we identified a fast- and a slow-converting microbiota that was subsequently inoculated to SHIME, a dynamic model of the human gut. Monitoring of microbial (+)-catechin metabolites from proximal and distal colon compartments with UHPLC-MS and UPLC-IMS-Q-TOF-MS revealed profound donor-dependent and colon-region-dependent metabolite profiles with 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone being the largest contributor to differences between the fast- and slow-converting microbiota and the distal colon being a more important region for (+)-catechin metabolism than the proximal colon. Our findings may contribute to further understanding the role of the gut microbiota as a determinant of interindividual variation in pharmacokinetics upon (+)-catechin ingestion.

Urinary Concentrations of (+)-Catechin and (-)-Epicatechin as Biomarkers of Dietary Intake of Flavan-3-ols in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.

This study examines the correlation of acute and habitual dietary intake of flavan-3-ol monomers, proanthocyanidins, theaflavins, and their main food sources with the urinary concentrations of (+)-catechin and (-)-epicatechin in the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (N = 419, men and women) provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day. Acute and habitual dietary data were collected using a standardized 24-HDR software and a validated dietary questionnaire, respectively. Intake of flavan-3-ols was estimated using the Phenol-Explorer database. Concentrations of (+)-catechin and (-)-epicatechin in 24-h urine were analyzed using tandem mass spectrometry after enzymatic deconjugation. Simple and partial Spearman’s correlations showed that urinary concentrations of (+)-catechin, (-)-epicatechin and their sum were more strongly correlated with acute than with habitual intake of individual and total monomers (acute rpartial = 0.13–0.54, p < 0.05; and habitual rpartial = 0.14–0.28, p < 0.01), proanthocyanidins (acute rpartial = 0.24–0.49, p < 0.001; and habitual rpartial = 0.10–0.15, p < 0.05), theaflavins (acute rpartial = 0.22–0.31, p < 0.001; and habitual rpartial = 0.20–0.26, p < 0.01), and total flavan-3-ols (acute rpartial = 0.40–0.48, p < 0.001; and habitual rpartial = 0.23–0.33, p < 0.001). Similarly, urinary concentrations of flavan-3-ols were weakly correlated with both acute (rpartial = 0.12–0.30, p < 0.05) and habitual intake (rpartial = 0.10–0.27, p < 0.05) of apple and pear, stone fruits, berries, chocolate and chocolate products, cakes and pastries, tea, herbal tea, wine, red wine, and beer and cider. Moreover, all comparable correlations were stronger for urinary (-)-epicatechin than for (+)-catechin. In conclusion, our data support the use of urinary concentrations of (+)-catechin and (-)-epicatechin, especially as short-term nutritional biomarkers of dietary catechin, epicatechin and total flavan-3-ol monomers.

Effects of catechin and copper or their combination in diet on productive performance, egg quality, egg shelf-life, plasma 8-OHdG concentrations and oxidative status in laying quail (Coturnix coturnix japonica)

ABSTRACT The aim of this study was to determine the effects of catechin and copper supplementations to quail diet on performance, egg quality and lipid peroxidation, plasma 8-hydroxydeoxyguanosine (8-OHdG) concentrations and oxidative status. In this study, 300 quails, 10-week old, were divided into 4 groups with 5 replicates. The dietary treatments were a control diet and a control diet supplemented with 3000 mg/kg of green tea catechins (Cat), 80 mg/kg of copper proteinate (CuP), or 3000 mg/kg of Cat + 80 mg/kg of CuP (combination; Cat + CuP) for 8 weeks. Plasma 8OHdG and enzyme activities did not change. Egg weight and specific gravity of Cat group were lower than that of the control group (p < 0.001). Egg yolk colour increased by dietary catechin (p = 0.001). The MDA concentrations in egg yolk, plasma and tissue decreased by dietary catechin; and kidney MDA concentrations also decreased by all treatments (p < 0.05). Consequently, dietary catechin had a negative effect on egg-specific gravity and a positive effect on egg yolk colour without affecting internal egg quality parameters. However, dietary catechin and copper, without causing DNA damage, reduced lipid peroxidation in egg and organism and has a positive effect on egg lipid peroxidation.

Antioxidative Effect of Dietary Tea Catechins on the Quality of Enulsified Pork Meatballs under Refrigeration

After meat products are heated and placed in storage, the lipid contained inside undergoes oxidation, which causes the meat to become malodorous and reduces its acceptability in the market. In this study, catechin was added to emulsified pork meatballs in the hope of reducing lipid oxidation. The influence that catechin additions at different concentrations (0, 400 and 800 ppm) have on the pH value, color, texture profiles, microbial testing, sensory analysis, thiobarbituric acid reactive substance value, and antioxidant capacity of the emulsified pork meatball is investigated in this study. The test results on lipid oxidation indicated that after 15 days of refrigerated storage at 4°C, oxidation in the control group was 2.46 mg malondialdehyde equal (MDA eq.)/kg meatball. The 400 ppm and 800 ppm of catechin-treated groups yielded 0.56 and 0.31 mg MDA eq./kg, respectively, which were significantly lower than the control group. The results were similar after 90 days of frozen storage at -20°C, where the 400 ppm and 800 ppm of catechin-treated groups yielded 0.60 and 0.25 mg MDA eq./kg, respectively, which were significantly lower than the oxidation level in the control group (1.39 mg MDA eq./kg). Regarding the antioxidant capacity tests, the meatballs that were treated with 400 ppm and 800 ppm of catechin displayed a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity of 1.31 and 1.97 mg of ascorbic acid/g, respectively, whereas the total antioxidant capacity was 2.63 and 4.53 mg of Trolox/g, respectively. The results of both groups were significantly higher than the DPPH radical scavenging capacity (0.07 mg as ascorbic acid/g) and the total antioxidant capacity (0.36 mg as Trolox/g) of the control group. After 90 days of frozen storage at -20°C, the antioxidant capacity of catechin-treated groups were still higher than the control group. The mentioned results indicate that adding catechin to emulsified pork meatballs inhibits lipid oxidation and can help boost the quality and functionality of these emulsified pork meatball products.

Association between dietary polyphenols intake and an oxidative stress biomarker: interest of multiple imputation for handling missing covariates and outcomes

We aimed to illustrate the importance of imputation models specifications, based on a study exploring the associations between subclasses of dietary polyphenols and the thiobarbituric-acid-reactive substances (TBARS). Data were collected in a long-term cohort study based on a double-blind randomized placebo-controlled nutritional trial (SU.VI.MAX 2 study). The association between polyphenols intakes and TBARS were studied using linear regression models. Missing data were handled using multiple imputation with chained equations. A total of 4,129 subjects were included in the analysis, 2,116 of whom had an available outcome measure (TBARS). Differences in selected predictors of TBARS according to the handling of missing data on both covariates and outcome (complete case analysis or multiple imputation) were observed. In the complete case analysis, none of the dietary polyphenol subclasses was found to be associated with TBARS while based on multiple imputed datasets, two polyphenol subclasses, namely catechins and hydroxybenzoic acids, could be selected as associated with TBARS. Of note, while there was a positive association between catechins and TBARS, the hydroxybenzoic acids were negatively associated with TBARS. Adequate modelling of missing data on both covariates and outcome allowed dietary catechins intake to be selected as associated with a biomarker of oxidative stress.

Catechin and quercetin attenuate adipose inflammation in fructose-fed rats and 3T3-L1 adipocytes.

This study evaluated the capacity of dietary catechin (C), quercetin (Q), and the combination of both (CQ), to attenuate adipose inflammation triggered by high fructose (HFr) consumption in rats and by tumor necrosis factor alpha (TNF-α) in 3T3-L1 adipocytes. In rats, HFr consumption for 6 wk caused dyslipidemia, insulin resistance, reduced plasma adiponectin, adiposity, and adipose tissue inflammation. Dietary supplementation with 20 mg/kg/day of C, Q, and CQ improved all these parameters. In 3T3-L1 adipocytes, C and Q attenuated TNF-α-induced elevated protein carbonyls, increased proinflammatory cytokine expression (MCP-1, resistin), and decreased adiponectin. The protective effects of C and Q on adipose inflammation are in part associated with their capacity to (i) decrease the activation of the mitogen-activated kinases (MAPKs) JNK and p38; and (ii) prevent the downregulation of PPAR-γ. In summary, C and Q, and to a larger extent the combination of both, attenuated adipose proinflammatory signaling cascades and regulated the balance of molecules that improve (adiponectin) or impair (TNF-α, MCP-1, resistin) insulin sensitivity. Together, these findings suggest that dietary Q and C may have potential benefits in mitigating MetS-associated adipose inflammation, oxidative stress, and insulin resistance.

Urinary biomarkers of catechins and risk of hepatocellular carcinoma in the Shanghai Cohort Study.

Dietary catechins are phytochemicals with both antioxidative and prooxidative stress properties. Green tea is a major source of catechins and may be associated with hepatocellular carcinoma (HCC) risk, but the catechin-HCC relationship has not been evaluated using a biomarker-based approach. A nested case-control study of HCC (211 cases and 1,067 matched controls) was conducted within the Shanghai Cohort Study, which enrolled 18,244 men between 1986 and 1989. Concentrations of specific catechins, including epicatechin, epigallocatechin (EGC), and 4'-O-methyl-epigallocatechin, were measured in urine specimens that had been collected prior to HCC diagnosis. None of the catechins measured were associated with HCC risk. In stratified analyses, there was a statistically significant trend for an association of higher urinary EGC with increased HCC risk among subjects with positive serology for hepatitis B surface antigen (P for trend = 0.02). This positive EGC-HCC association became stronger for hepatitis B surface antigen-positive persons who also had low serum retinol levels (for detectable levels vs. undetectable levels, odds ratio = 2.62, 95% confidence interval: 1.25, 5.51). There was no evidence supporting a protective role of catechins in the development of HCC. Instead, exposure to high levels of catechins may increase the risk of developing HCC for high-risk individuals.

Influence of galloyl moiety in interaction of epicatechin with bovine serum albumin: a spectroscopic and thermodynamic characterization.

The health benefits stemming from green tea are well known, but the exact mechanism of its biological activity is not elucidated. Epicatechin (EC) and epicatechin gallate (ECG) are two dietary catechins ubiquitously present in green tea. Serum albumins functionally carry these catechins through the circulatory system and eliminate reactive oxygen species (ROS) induced injury. In the present study ECG is observed to have higher antioxidant activity; which is attributed to the presence of galloyl moiety. The binding affinity of these catechins to bovine serum albumin (BSA) will govern the efficacy of their biological activity. EC and ECG bind with BSA with binding constants 1.0×106 M−1 and 6.6×107 M−1, respectively. Changes in secondary structure of BSA on interaction with EC and ECG have been identified by circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy. Thermodynamic characterization reveals the binding process to be exothermic, spontaneous and entropy driven. Mixed binding forces (hydrophobic, electrostatic and hydrogen bonding) exist between ECG and BSA. Binding site for EC is primarily site-II in sub-domain IIIA of BSA and for ECG; it is site-I in sub-domain IIA. ECG with its high antioxidant activity accompanied by high affinity for BSA could be a model in drug designing.

마이크로웨이브를 조사한 흰쥐 폐조직의 Phospholipae A2활성과 Arachidonic Acid Cascade계에 미치는 녹차 Catechin의 영향

본 연구에서는 흰쥐에 마이크로웨이브를 조사한 후 폐조직을 대상으로 폐조직 기능장애를 일으키는데 주된 역할을 하는 혈전생성능을 arachidonic acid(AA) cascade계를 통해 관찰하여 마이크로웨이브에 의한 폐혈관 기능장애와 그에 대한 녹차 catechin의 항혈전 효과를 규명하고자 하였다. 실험군은 마이크로웨이브를 조사하지 않은 정상군과 마이크로웨이브를 조사한 군으로 나누고 마이크로웨이브 조사 군은 다시 식이 중 catechin 공급수준에 따라 catechin을 넣지 않은 군(MW group), catechin을 0.25% 급여한 군(MW-0.25C group), catechin을 0.5% 급여한 군(MW-0.5C group)으로 나누었다. 식이와 음료는 자유 섭식시키면서 2주간 사육한 후 2.45 GHz 대역의 주파수를 15분간 1회 조사하였으며 마이크로웨이브 조사 후 6일째 동물을 희생시켜 본 실험에 사용하였다. 실험군의 실험동물 수는 각각 10마리로 실험하였다. PLA2 활성은 마이크로웨이브 조사로 30% 증가하였으며 MW-0.25C군은 15% 증가였으나 MW-0.5C군은 정상군 수준이었다. 인지질분자종의 변화를 관찰한 결과 lyso PE가 MW군에서 47% 증가되었으나 MW-0.25C군 및 MW-0.5C군에서는 각각 18%, 20% 증가되었다. TXA₂ 생성은 MW군에서 50%의 현저한 증가를 보였으나 catechin 공급군인 MW-0.25C군 및 MW-0.5C군은 정상군 수준이었다. PGI₂ 생성은 MW군에서 31%의 유의적인 감소를 보였으나 catechin 공급군인 MW-0.25C군 및 MW-0.5군은 정상군 수준이었다. 따라서 혈전생성지표인 PGI2/TXA2 ratio는 정상군에 비해 MW군에서 43% 유의적으로 감소되었으나 MW-0.25C군 및 MW-0.5C군은 정상군 수준이었다. 지질과산화물의 함량은 MW군에서 34% 유의적으로 증가하였으며 catechin 공급군은 정상군 수준이었다. 결론적으로 마이크로웨이브에 피폭된 흰쥐 폐조직에서는 AA cascade계의 율속 효소인 PLA₂ 활성의 증가와 혈전생성지표로 인식하는 PGI₂/TXA₂ ratio의 불균형이 초래되었으나 catechin은 TBARS 농도를 낮추면서 PLA₂ 활성을 저해시키고 AA cascade계를 개선시킴으로써 항혈전 작용을 나타내었다.

Pulse radiolysis study of the reactions of catechins with nitrogen dioxide

Nitrogen dioxide (•NO2), one of the oxidizing radicals formed in vivo is suspected to play a role in various pathophysiological processes. The reactions of •NO2 with dietary catechins, the group of flavonoids present in high amounts in green tea and red wine, have been investigated by pulse radiolysis method. The kinetics of the reaction of •NO2 with gallic acid have been also studied for comparison. The spectra of transient intermediates are presented. The rate constants of the reaction of •NO2 with catechin, epigallocatechin, epigallocatechin gallate and gallic acid determined by the competition method with 2,2’-azinobis-(3-ethylbenzthiazoline-6-sulfonate) at pH 7.0 and room temperature have been found to be 0.9, 1.0, 2.3 and 0.5×108M−1s−1, respectively. The values for catechins are among the highest reported for the reactions of •NO2 with non-radical compounds.

In vitro evaluation of the antioxidant and anti-inflammatory activities of sulphated metabolites of catechins Evaluación in vitro de las actividades antioxidante y antiinflamatoria de metabolitos sulfatados de catequinas

Catechins are major polyphenols in many plant foods that have been related to health promotion. In the human organism, they are largely metabolised to different conjugated metabolites (i.e. glucuronide, sulphate and methylated derivatives), which are further found in plasma and would be thus able to reach the biological targets. Therefore, in vitro assays aiming to elucidate the biological effects of dietary catechins should also consider their metabolites and not only the original compounds. In this article, the in vitro antioxidant and anti-inflammatory activities of different catechin and epicatechin sulphates, one of the less studied catechin metabolites, have been evaluated. Since these compounds are not commercially available, they had to be first synthesised in the laboratory. The in vitro antioxidant activity was assessed using the ferric reducing power (FRAP) assay and two methods based on the ability to scavenge the ABTS•+ radical cation at different pH values. Sulphation of (epi)catechin lead to a decrease in the antioxidant activity that was greater when the sulphate moiety was located in the catechin B-ring than in A-ring. Despite this, all the studied (epi)catechin sulphates still behave as better antioxidants than α-tocopherol in the radical scavenging assays carried out at pH 7.4, suggesting that they might act as efficient antioxidants in physiological conditions. The anti-inflammatory potential was assessed by evaluating the ability of the compounds to reduce the concentration of nitric oxide (NO) secreted by macrophages (RAW 264.7) after activation with a bacterial lipopolysaccharide (LPS). In the range of studied concentrations (1–300 μM), all the (epi)catechin sulphates caused a dose-dependent inhibition in NO production that even slight was statistically significant in most cases in relation to controls (LPS-activated cells without catechins), whereas the parent catechins did not show any effect in NO production in our experimental conditions. None of the assayed compounds showed any cytotoxic effect in macrophages up to the highest concentration used (300 μM). The obtained results suggested possible antioxidant and immuno-modulatory roles of the sulphated metabolites of catechins. Las catequinas son polifenoles mayoritarios en muchos alimentos vegetales y han sido relacionadas con la promoción de la salud. En el organismo humano son biotransformadas a diferentes metabolitos conjugados (glucurónidos, sulfatos y derivados metilados), que aparecen luego en plasma y serían, por tanto, capaces de alcanzar los potenciales objetivos biológicos. Por ello, los ensayos in vitro que tratan de esclarecer los efectos biológicos de las catequinas de la dieta deben considerar también estos metabolitos y no sólo los compuestos originales. En este trabajo se han evaluado las actividades antioxidante y antiinflamatoria in vitro de diferentes sulfatos de catequina y epicatequina, un tipo de metabolitos apenas estudiados. Estos compuestos no están disponibles comercialmente, por lo que fueron sintetizados en el laboratorio. La actividad antioxidante se evaluó mediante el método FRAP y dos métodos basados en la capacidad para captar el radical ABTS•+ a dos valores diferentes de pH (4,5 y 7,4). Se observó que la sulfatación produce una disminución en la actividad antioxidante de las catequinas, mayor cuando el grupo sulfato se encuentra en el anillo B que en el A. No obstante, todos los sulfatos estudiados se comportan como mejores antioxidantes que el α-tocoferol en el ensayo realizado a pH 7,4, sugiriendo que podrían actuar como antioxidantes eficaces en situación fisiológica. La actividad antiinflamatoria se evaluó a partir de la capacidad de los compuestos para reducir la concentración de óxido nítrico (NO) secretada por macrófagos (RAW 264,7) tras su activación con lipopolisacárido bacteriano (LPS). En el intervalo de concentraciones estudiadas (1–300 μM) todos los sulfatos de (epi)catequina producían una inhibición en la formación de NO dosis-dependiente pequeña pero estadísticamente significativa con relación a los controles (células activadas con LPS sin catequina), mientras que la catequinas originales no tenían ningún efecto en la producción de NO. Ninguno de los compuestos ensayados mostró efectos citotóxicos en los macrófagos hasta la concentración máxima ensayada (300 μM). Los resultados obtenidos sugieren un posible papel antioxidante e inmuno-modulador de los metabolitos sulfatados de catequinas.

Isolation of catechin-converting human intestinal bacteria

To isolate and characterize bacteria from the human intestine that are involved in the conversion of catechins, a class of bioactive polyphenols abundant in the human diet. Two bacterial strains, rK3 and aK2, were isolated from an epicatechin-converting human faecal suspension. The isolates catalysed individual steps in the degradation of ⁻-epicatechin and ⁺-catechin. Based on their phenotypic characteristics and 16S rRNA gene sequences, the isolates were identified as Eggerthella lenta and Flavonifractor plautii (formerly Clostridium orbiscindens). Eggerthella lenta rK3 reductively cleaved the heterocyclic C-ring of both ⁻-epicatechin and ⁺-catechin giving rise to 1-(3,4-dihydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propan-2-ol. The conversion of catechin proceeded five times faster than that of epicatechin. Higher (epi)catechin concentrations led to an accelerated formation of the ring fission product without affecting the growth of Eg. lenta rK3. Flavonifractor plautii aK2 further converted 1-(3,4-dihydroxyphenyl)-3-(2,4,6-trihydroxyphenyl)propan-2-ol to 5-(3,4-dihydroxyphenyl)-γ-valerolactone and 4-hydroxy-5-(3,4-dihydroxyphenyl)valeric acid. Flavonifractor plautii DSM 6740 catalysed the identical reaction indicating it is not strain specific. The conversion of dietary catechins by the isolated Eg. lenta and F. plautii strains in the human intestine may affect their bioavailability. The majority of catechin metabolites are generated by the intestinal microbiota. The identification of catechin-converting gut bacteria therefore contributes to the elucidation of the bioactivation and the health effects of catechins.

Dietary catechins and procyanidins modulate zinc homeostasis in human HepG2 cells

Catechins and their polymers procyanidins are health-promoting flavonoids found in edible vegetables and fruits. They act as antioxidants by scavenging reactive oxygen species and by chelating the redox-active metals iron and copper. They also behave as signaling molecules, modulating multiple cell signalling pathways and gene expression, including that of antioxidant enzymes. This study aimed at determining whether catechins and procyanidins interact with the redox-inactive metal zinc and at assessing their effect on cellular zinc homeostasis. We found that a grape-seed procyanidin extract (GSPE) and the green tea flavonoid (−)-epigallocatechin-3-gallate (EGCG) bind zinc cations in solution with higher affinity than the zinc-specific chelator Zinquin, and dose-dependently prevent zinc-induced toxicity in the human hepatocarcinoma cell line HepG2, evaluated by the lactate dehydrogenase test. GSPE and EGCG hinder intracellular accumulation of total zinc, measured by atomic flame absorption spectrometry, concomitantly increasing the level of cytoplasmic labile zinc detectable by Zinquin fluorescence. Concurrently, GSPE and EGCG inhibit the expression, evaluated at the mRNA level by quantitative reverse transcriptase-polymerase chain reaction, of zinc-binding metallothioneins and of plasma membrane zinc exporter ZnT1 (SLC30A1), while enhancing the expression of cellular zinc importers ZIP1 (SLC39A1) and ZIP4 (SLC39A4). GSPE and EGCG also produce all these effects when HepG2 cells are stimulated to import zinc by treatment with supplemental zinc or the proinflammatory cytokine interleukin-6. We suggest that extracellular complexation of zinc cations and the elevation of cytoplasmic labile zinc may be relevant mechanisms underlying the modulation of diverse cell signaling and metabolic pathways by catechins and procyanidins.

Abstract 4376: Biological, biochemical, and molecular targets for dietary catechin-induced suppression of breast cell chronic carcinogenesis

Abstract This study is to identify biological, biochemical, and molecular targets for dietary catechins in early prevention of breast cell carcinogenesis induced chronically by environmental carcinogens. Breast cell carcinogenesis is a multiyear, multistep, and multipath disease process and is the most common type of cancer among women in northern America and northern Europe. Epidemiologic and experimental evidence suggests that dietary constituents in fruits and vegetables prevent human cancers; dietary prevention is a cost-efficient strategy to reduce the risk of this disease. However, the mechanisms for dietary prevention of cellular carcinogenesis induced by chronic exposure to environmental carcinogens remain to be elucidated. To identify dietary components for prevention of chronic human breast cell carcinogenesis, we studied biological, biochemical, and molecular target endpoints that were induced by low doses of carcinogens and suppressed by dietary catechins. Immortalized, non-cancerous human breast epithelial MCF10A cells were repeatedly exposed to carcinogens 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or benzo[α]pyrene (B[α]P), each at picomolar concentrations, to induce cancer-associated biological, biochemical, and molecular properties in cells. We then used these changes as target endpoints to reveal the activity of various dietary catechins in suppression of NNK- and B[α]P-induced cellular carcinogenesis. We identified that cells acquiring the biological properties of reduced dependence on growth factors, anchorage-independent growth, and acinar-conformational disruption were reduced by treatment with dietary catechins. We identified that hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2) played a novel role in NNK- and B[α]P-induced cellular carcinogenesis, and its expression acted as a molecular target endpoint in catechin-induced suppression of cellular carcinogenesis. The ability of catechins to reduce gene expression of cytochrome P450 enzymes CYP1A1 and CYP1B1, which can bioactivate NNK and B[α]P, may be involved in the preventive mechanism for catechins in suppression of cellular carcinogenesis. Our model system with biological, biochemical, and molecular target endpoints verified the value of dietary catechins for prevention of human breast cell carcinogenesis induced by repeated exposures to low doses of multiple environmental carcinogens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4376.

Effects of Quercetin and Catechin on Hepatic Glutathione-S Transferase (GST), NAD(P)H Quinone Oxidoreductase 1 (NQO1), and Antioxidant Enzyme Activity Levels in Rats

Cell culture data indicate that quercetin and catechin may affect the activity of phase II and antioxidant enzymes. However, little is known about the impact of dietary flavonoids in vivo. Therefore, the present study aimed to investigate the in vivo effects of the flavonoids quercetin and catechin on mRNA and activity levels of phase II enzymes glutathione-S transferase (GST) and NAD(P)H quinone oxidoreductase-1 (NQO1) in rat liver. Furthermore, the activity of the hepatic antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) was determined. Feeding male Wistar rats (3 × 6 animals) over 3 wk with semisynthetic diets enriched with quercetin and catechin (2 g/kg diet) did not affect liver enzyme activity of CAT, GPx, and SOD as well lipid peroxidation and glutathione levels. Dietary quercetin significantly decreased activity of hepatic GST (24%), whereas dietary catechin significantly decreased NQO1 activity (26%) compared to controls. Changes in GST and NQO1 activity were partly reflected on mRNA levels. Current data indicate that dietary flavonoids have little effects on liver oxidant/antioxidant status but do significantly affect the phase II enzymes GST and NQO1 in rat liver. This in turn may affect the ability of the organism to detoxify endogenous and exogenous xenobiotics.

Dietary flavonol, flavone and catechin intake and risk of colorectal cancer in the Netherlands Cohort Study

Dietary flavonoids are hypothesized to be protective against colorectal cancer, yet findings have been inconsistent. We examined the association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints within the Netherlands Cohort Study (NLCS). In addition, we explored whether body mass index (BMI) may be an effect modifier of this association. The NLCS includes 120,852 men and women who were 55-69 years and completed a self-administered questionnaire at baseline in 1986. A case-cohort approach was used for data processing and analysis. After 13.3 years, 1,444 male and 1,041 female colorectal cancer cases were available for estimation of hazard ratios and 95% confidence intervals for quintiles of flavonoid intake. After adjustment for potential confounders, no association of total flavonol and flavone intake and total catechin intake with colorectal cancer endpoints was observed. Analyses stratified for BMI showed significant inverse trends in the association of total catechin intake, (+)-catechin intake and (-)-epicatechin intake with rectal cancer in men with a BMI>or=25 kg/m2 and in the association of total catechin intake and intake of kaempferol, myricetin and all individual catechins with colorectal cancer, in particular colon cancer, in women with a BMI<25 kg/m2. In conclusion, our findings generally do not support an association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints. Dietary catechin intake may be associated with a decreased rectal cancer risk in overweight men. Dietary flavonol and catechin intake may be associated with a decreased colorectal cancer risk in normal weight women.

Physiological levels of tea catechins increase cellular lipid antioxidant activity of vitamin C and vitamin E in human intestinal Caco-2 cells

Oxidative stress has been linked to the development of various chronic diseases. Vegetables and fruits, which contain polyphenols, were shown to have protective effects. (−)-Epigallocatechin-3-gallate (EGCG), a polyphenol abundant in tea, has been shown to have antioxidant activities in cell-free conditions and this study focused on the effect of cellular EGCG. Using an intestinal cell model to examine the oxidative stress induced by hydroxyl radicals, we report here that physiological concentrations (0.1–1 μM) of EGCG have dose- and incubation duration-dependent cell-associated lipid antioxidant activity (measuring malondialdehyde production). Vitamin E and vitamin C at 10–40 μM also showed cell-associated lipid antioxidant activities under shorter incubation durations. When EGCG was included in the incubation with vitamin E or C, more antioxidant activities were consistently observed than when vitamins were added alone. Catechin (widely present in fruits and vegetables) at 1 μM also significantly increased the antioxidant activity of vitamins E and C. Previous studies examining cell-associated activity of EGCG mainly focused on the 10–100 μM concentration range. Our results suggest that although the physiological level (0.1–1 μM) of dietary catechins is much lower than that of vitamins, they further contribute to the total antioxidant capacity even in the presence of vitamins.