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(-)-Epicatechin (EPI) is beneficial for cardiovascular health. Trimethylamine N-oxide (TMAO), a gut microbe-derived food metabolite, is strongly associated with the risk of cardiovascular diseases. However, the effects and underlying mechanisms of EPI on TMAO-induced cardiac hypertrophy remain unclear. This study aimed to determine whether EPI inhibits TMAO-induced cardiac hypertrophy. Plasma levels of TMAO in control participants and patients with cardiac hypertrophy were measured and analyzed. Male C57BL/6 mice were randomly divided into control group, TMAO group, EPI group and TMAO + EPI group. According to the groups assignments, mice received intraperitoneal (i.p.) injection of normal saline or i.p. injection of TMAO (150 mg/kg/day) for 14 days. The EPI group was given intragastric (i.g.) administration of EPI alone (1 mg/kg/day) for 21 days, and TMAO + EPI group received i.g. administration of EPI for 7 days before starting i.p. injection of TMAO, continuing until the end of the TMAO treatment. Histological analyses of the mice's hearts was accessed by H&E and Masson staining. In vitro, H9c2 cells were induced to hypertrophy by TMAO (10 µM) for 24 h and were pre-treated with or without EPI (10 µM) for 1 h. Protein level of cardiac hypertrophy markers and Sp1/SIRT1/SUMO1 pathway were determined by western blot. The plasma level of TMAO was 2.66 ± 1.59 μmol/L in patients with cardiac hypertrophy and 0.62 ± 0.30 μmol/L in control participants. EPI attenuated TMAO-induced hypertrophy in H9c2 cells. In vivo, TMAO induced cardiac hypertrophy and impaired the cardiac function of mice. Pathological staining showed that TMAO induced cardiac hypertrophy and collagen deposition in mice. EPI treatment improved the cardiac function, inhibited the myocardial hypertrophy induced by TMAO. EPI significantly attenuated the TMAO-induced upregulation of ANP and BNP and the downregulation of SP1, SIRT1 and SUMO1 in vivo and in vitro. EPI may suppress TMAO-induced cardiac hypertrophy by activating the Sp1/SIRT1/SUMO1 signaling pathway., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical Approval The study was approved by the Institutional Ethics Committees of the First Affiliated Hospital of Harbin Medical University (No. IRB-AF/SC-08/05.0). The present study was conducted according to the “Guide for the Care and Use of Laboratory Animals” (NIH Publication No.85-23, revised in 1996). The animal experiments were approved by the Institutional Animal Care and Use Committee of First Affiliated Hospital, Harbin Medical University. Consent to Participate The study protocols and the procedures for handling human samples were approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (Harbin, China). All patients provided informed consent, and all the methods were carried out in accordance with the approved guidelines. Consent for Publication Not applicable., (© 2024. The Author(s).)

The primary aim of this research was to identify the structural characteristics of three newly derived procyanidins from cold plasma-treated (-)-epicatechin, known for their anti-inflammatory properties. The newly generated compounds were isolated through column chromatography, and their chemical structures were elucidated through spectroscopic data analyses, including both one-dimensional and two-dimensional nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. Furthermore, their absolute configurations were determined via circular dichroism (CD) spectroscopy. The inhibitory activity of the isolated compounds on nitric oxide (NO) production and expression levels of inducible NO synthase (iNOS) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages was evaluated. Three new procyanidins-methylenetrisepicatechin ( 2 ), isomethylenetrisepicatechin ( 3 ), and methylenebisepicatechin ( 4 )-along with two reported dimeric flavan-3-ols ( 5 and 6 ), were identified from plasma-treated (-)-epicatechin ( 1 ). The unique oligomerized products 2 and 3 linked by methylene bridges significantly suppressed both NO production and iNOS expression, demonstrating higher anti-inflammatory activities in LPS-stimulated RAW 264.7 cells compared with the parent compound. The newly oligomerized procyanidins have potential applications in the treatment of inflammatory diseases owing to their significant anti-inflammatory properties.

The aim of this study was to analyse the expression of genes related to the regulation of energy metabolism in skeletal muscle tissue by comparing male offspring in two age groups [at 110 and 245 postnatal days (pnd)] from a mother with obesity induced by a high-fat diet and (-)-epicatechin (Epi) administration. Four groups of six male offspring from different litters were randomly selected for the control groups [C and offspring of mothers with maternal obesity (MO)] or Epi intervention groups. We evaluated the effect of Epi on gastrocnemius tissue by analysing the mRNA and protein expression levels of Fndc5/irisin, Pgc-1α, Ucp3, and Sln. Epi significantly increased the Pgc-1α protein in the MO group of offspring at 110 pnd ( p < 0.036, MO vs . MO+Epi), while at 245 pnd, Epi increased Fndc5/irisin mRNA expression in the MO+Epi group versus the MO group ( p = 0.006).No differences were detected in Fndc5/irisin, Ucp3 or Sln mRNA or protein levels (including Pgc-1α mRNA) in the offspring at 110 pnd or in Pgc-1α, Ucp3, or Sln mRNA or protein levels (including Fndc5/irisin protein) at 245 pnd among the experimental groups. In conclusion, (-)-epicatechin treatment increased Fndc5/irisin mRNA expression and Pgc-α protein levels in the gastrocnemius muscle of offspring at postnatal days 110 and 245. Furthermore, it is suggested that the flavonoid effect in a model of obesity and its impact on thermogenesis in skeletal muscle are regulated by a different pathway than Fndc5/irisin.

Background: Acanthamoeba is an opportunistic pathogen that can cause human infections such as granulomatous amebic encephalitis and acanthamoeba keratitis. However, no specific drug to treat the diseases has been developed. Therefore, the discovery or development of novel drugs for treating Acanthamoeba infections is urgently needed. The anti-protozoan activity of (‒)-epicatechin (EC) has been reported, suggesting it is an attractive anti-protozoal drug candidate. In this study, the amoebicidal activity of EC against A. castellanii was assessed and its mechanism of action was unveiled., Methods: The amoebicidal activity of EC against A. castellanii trophozoites and the cytotoxicity of EC in HCE-2 and C6 cells were determined with cell viability assay. The underlying amoebicidal mechanism of EC against A. castellanii was analyzed by the apoptosis/necrosis assay, TUNEL assay, mitochondrial dysfunction assay, caspase-3 assay, and quantitative reverse transcription polymerase chain reaction. The cysticidal activity of EC was also investigated., Results: EC revealed amoebicidal activity against A. castellanii trophozoites with an IC 50 of 37.01 ± 3.96 µM, but was not cytotoxic to HCE-2 or C6 cells. EC induced apoptotic events such as increases in DNA fragmentation and intracellular reactive oxygen species production in A. castellanii. EC also caused mitochondrial dysfunction in the amoebae, as evidenced by the loss of mitochondrial membrane potential and reductions in ATP production. Caspase-3 activity, autophagosome formation, and the expression levels of autophagy-related genes were also increased in EC-treated amoebae. EC led to the partial death of cysts and the inhibition of excystation., Conclusion: EC revealed promising amoebicidal activity against A. castellanii trophozoites via programmed cell death events. EC could be a candidate drug or supplemental compound for treating Acanthamoeba infections., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Aim: (-)-Epicatechin (EPI) has physiological activities such as antioxidant, anti-inflammatory and immune enhancement. In this study, we elucidated the protective effects of EPI in myocardial ischemia/reperfusion injury (MI/RI) and its mechanisms., Methods: An in vivo I/R model was constructed by performing left anterior descending coronary artery surgery on rats, and an in vitro I/R model was constructed by subjecting hypoxia/reperfusion treatment on H9C2 cells. The damage of cardiac tissues was detected by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (H&E) staining, and expressions of ferroptosis-related proteins were examined by Western blot. Changes in the number of autophagosomes, the levels of oxidative stress and Fe 2+ were also examined., Results: EPI reduced abnormal electrocardiogram waveform and infarct size caused by MI/RI in rats. The increasing trend of levels of reactive oxygen species (ROS) and Fe 2+ was reversed by EPI, suggesting that EPI can reduce ferroptosis in vivo . Moreover, the levels of lipid ROS and LC3 in H9C2 cells were decreased with EPI treatment, and autophagy and ferroptosis were also alleviated in a dose-dependent manner in vitro . Co-cultivation of USP14 inhibitor IU1 and EPI further revealed that EPI regulates ferroptosis through the USP14-autophagy pathway., Conclusions: EPI can reduce the level of oxidative stress by promoting USP14 to reduce autophagy, thus inhibiting autophagy dependent ferroptosis and reducing oxidative stress, and has a protective effect on myocardial infarction/myocardial infarction.

MurC, D, E, and F are ATP-dependent ligases involved in the stepwise assembly of the tetrapeptide stem of forming peptidoglycan. As highly conserved targets found exclusively in bacterial cells, they are of significant interest for antibacterial drug discovery. In this study, we employed a computer-aided molecular design approach to identify potential inhibitors of MurF. A biochemical inhibition assay was conducted, screening twenty-four flavonoids and related compounds against MurC-F, resulting in the identification of quercitrin, myricetin, and (-)-epicatechin as MurF inhibitors with IC 50 values of 143 µM, 139 µM, and 92 µM, respectively. Notably, (-)-epicatechin demonstrated mixed type inhibition with ATP and uncompetitive inhibition with D-Ala-D-Ala dipeptide and UM3DAP substrates. Furthermore, in silico analysis using Sitemap and subsequent docking analysis using Glide revealed two plausible binding sites for (-)-epicatechin. The study also investigated the crucial structural features required for activity, with a particular focus on the substitution pattern and hydroxyl group positions, which were found to be important for the activity. The study highlights the significance of computational approaches in targeting essential enzymes involved in bacterial peptidoglycan synthesis., (© 2023. The Author(s).)

(-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids and is widely distributed in the plant kingdom. Several studies have shown the beneficial effects of EC consumption. Many of these reported effects are exerted by activating the signaling pathways associated with the activation of two specific receptors: the G protein-coupled estrogen receptor (GPER), a transmembrane receptor, and the pregnane X receptor (PXR), which is a nuclear receptor. However, the effects of EC are so diverse that these two receptors cannot describe the complete phenomenon. The apelin receptor or APLNR is classified within the G protein-coupled receptor (GPCR) family, and is capable of activating the G protein canonical pathways and the β-arrestin transducer, which participates in the phenomenon of receptor desensitization and internalization. β-arrestin gained interest in selective pharmacology and mediators of the so-called "biased agonism". With molecular dynamics (MD) and in vitro assays, we demonstrate how EC can recruit the β-arrestin in the active conformation of the APLN receptor acting as a biased agonist.

(-)-Epicatechin, a flavonoid present in high concentrations in foods such as green tea and cocoa, exerts beneficial and protective effects in numerous disease models, including anti-tumorigenesis and apoptosis in human breast and prostate cancer cells. Potential interactions of (-)-epicatechin and (+)-catechin with the membrane androgen receptor, ZIP9 (SLC39A9), which mediates androgen induction of apoptosis in these cancer cells, were investigated. Both (-)-epicatechin and (+)-catechin were effective competitors of [ 3 H]-testosterone binding to PC-3 prostate cancer cells (nuclear androgen receptor-negative, nAR-null) overexpressing ZIP9 (PC3-ZIP9), with relative binding affinities of 75 % and 28 % that of testosterone, respectively. (-)-Epicatechin (200 nM) mimicked the effects of 100 nM testosterone in inducing apoptosis of PC3-ZIP9 cells, whereas (+)-catechin (concentration range 200 nM-1000 nM) did not significantly increase apoptosis and instead blocked the apoptotic response to testosterone. (-)-Epicatechin also activated androgen-dependent ZIP9 signaling pathways, inducing decreases in cAMP production and elevating intracellular free zinc levels, while (+)-catechin typically lacked these actions. Both (-)-epicatechin and (+)-catechin also bound to cell membranes of MDA-MB-468 breast cancer cells (nAR-null, high ZIP9 expression). MDA-MB-468 cells showed similar apoptotic, cAMP, and free zinc signaling responses to (-)-epicatechin to those observed in PC3-ZIP9 cells, as well as antagonism by (+)-catechin of testosterone-induced apoptosis and modulation of cAMP and caspase-3 levels. Moreover, knockdown of ZIP9 expression in MDA-MB-468 cells with siRNA decreased specific [ 3 H]-testosterone binding of both catechins and blocked the apoptotic and free zinc responses to testosterone and (-)-epicatechin. The results indicate (-)-epicatechin is a potent ZIP9 agonist in breast and prostate cancer cells., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Generated in intestinal L cells through cleavage of proglucagon (Gcg), glucagon-like peptide 1 (GLP-1) is secreted and rapidly inactivated by dipeptidyl peptidase IV (DPP-IV). GLP-1 regulates insulin secretion and overall glucose homeostasis. The capacity of dietary bioactives to increase GLP-1 circulating levels, and therefore increase insulin secretion and glucose metabolism, has gained significant interest of late., Objectives: We evaluated the effects of (-)-epicatechin (EC) and different anthocyanins (ACs) and AC metabolites on GLP-1 metabolism in mice and on GLUTag cells., Methods: We fed 6-week-old C57BL/6J male mice a control diet or a control diet supplemented with either 40 mg AC or 20 mg EC/kg body weight for 14 weeks (AC) or 15 weeks (EC). Intestinal mRNA levels of Gcg and Dpp-iv were measured. In vitro, GLUTag cells were incubated in the presence or absence of different ACs, the AC metabolite protocatechuic acid (PCA), and EC. GLP-1 secretion and the main pathways involved in its release were assessed., Results: Long-term supplementation with EC or AC increased mouse GLP-1 plasma concentrations (55% and 98%, respectively; P < 0.05). In mice, 1) EC and AC increased Gcg mRNA levels in the ileum (91%) and colon (41%), respectively (P < 0.05); and 2) AC lowered ileum Dpp-iv mRNA levels (35%), while EC decreased plasma DPP-IV activity (15%; P < 0.05). In GLUTag cells, 1) cyanidin, delphinidin, PCA, and EC increased GLP-1 secretion (53%, 33%, 53%, and 68%, respectively; P < 0.05); and 2) cyanidin, delphinidin, EC, and PCA increased cyclin adenosine monophosphate levels (25-50%; P < 0.05) and activated protein kinase A (PKA; 100%, 50%, 80%, and 86%, respectively; P < 0.05)., Conclusions: In mice, EC and ACs regulated different steps in GLP-1 regulation, leading to increased plasma GLP-1. Cyanidin, delphinidin, PCA, and EC promoted GLP-1 secretion from GLUTag cells by activating the PKA-dependent pathway. These findings support the beneficial actions of these flavonoids in sustaining intestinal and glucose homeostasis through the modulation of the GLP-1 metabolism., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

In this work the effect of (-)-epicatechin on the development of amebic liver abscess in hamsters was evaluated. (-)-epicatechin is a flavonoid present in plants that possesses various biological properties, including its activity against some protozoal parasites; however its antiamebic activity in a living model had not been evaluated. Syrian golden hamsters were intrahepatically inoculated with 1x10 6 E. histolytica trophozoites, three days after inoculation they received nine intraperitoneal doses of (-)-epicatechin (10 mg/100 g) every 48 h. Animals without treatments and treated with metronidazole were included as controls. Macroscopic characteristics of the hepatic abscess, histopathological analysis of the tissue and the levels of inflammatory cytokines were determined. (-)-epicatechin produced a decrease in liver abscess progression being observed only 9.49% of damage compared to 84% shown by untreated animals. During treatment with (-)-epicatechin hepatic tissue showed signs of liver repair and absence of amoebae. Additionally, (-)-epicatechin produced a modulating effect on inflammatory cytokines TNF-α, IL-1β and IL-10. All these events observed in animals treated with (-)-epicatechin could contribute to the elimination of trophozoites and liver healing., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Metabolic syndrome is a condition whose incidence has been increasing around the world. It promotes a metabolic state of chronic systemic inflammation, correlated to cellular stress and genetic mutations, and subsequently with deadly chronic diseases, such as type 2 diabetes mellitus, cardiovascular diseases, and cancer. A randomized placebo-controlled study (n = 156) was conducted to determine the effects of consuming an enriched bread with 0.05% of a 1:1 mixture of (-)-epicatechin and quercetin on anthropometric and biochemical parameters of the participants. As a result, total cholesterol, LDL-cholesterol, total triglycerides, and fasting plasma glucose significantly decreased after three months of daily enriched bread consumption. Nuclear abnormalities in buccal epithelium cells also decreased (15.8 ± 3.2 down to 8.3 ± 1.0), showing a genoprotective effect. The antioxidant properties of these compounds were observed by monitoring changes in the cytoplasmic redox tone of intact Caco-2 cells expressing HyPer, a fluorescent redox biosensor. The combination of (-)-epicatechin and quercetin changes the cytoplasmic redox ambient in living cells and significantly improves biochemical parameters related to metabolic syndrome, and decreases the number of cell abnormalities in buccal epithelium cells of patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Methods: Relevant potential targets for EC were obtained based on Traditional Chinese Medicine System Pharmacology Database (TCMSP), a bioinformatics analysis tool for molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM) and STITCH databases. The Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were utilized to screen the known POI-related targets, while Cytoscape software was used for network construction and visualization. Then, the Gene Ontology (GO) and pathway enrichment analysis were carried out by the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Furthermore, KGN cells were performed to validate the predicted results in oxidative stress (OS) model, and antioxidant effect was examined., Results: A total of 70 potential common targets for EC in the treatment of POI were obtained through network pharmacology. Metabolic process, response to stimulus and antioxidant activity occupied a leading position of Gene Ontology (GO) enrichment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that PI3K/protein kinase B (AKT), TNF, estrogen, VEGF and MAPK signaling pathways were significantly enriched. In addition, cell experiments showed that EC exhibited antioxidant effects in an H2O2-mediated OS model in ovarian granulosa cells by regulating the expression of PI3K/AKT/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and multiple downstream antioxidant enzymes., Conclusion: EC could regulate multiple signaling pathways and several biological processes (BPs). EC had the ability to down-regulate elevated OS level through the PI3K/AKT/Nrf2 signaling pathway and represented a potential novel treatment for POI., (© 2021 The Author(s).)

Objective: To determine whether (-)-epicatechin (Epi) could decrease visceral adipose tissue and improve the metabolic profile of male offspring rats, after maternal obesity was induced by a high-fat diet (HFD)., Design: Maternal obesity in albino Wistar rats was induced with a HFD, whereas male offspring were fed with chow diet throughout the study. Eight male offspring per group, from different litters, were randomly assigned to the experimental or to the control groups. In the experimental group, Epi was administered at a dose of 1 mg/kg of body weight to the male offspring twice daily for two weeks, beginning at postnatal day (PND)., Main Measures: Weight of visceral adipose tissue, adipocyte size, and several metabolic parameters., Results: Epi administration in the male offspring induced a significant decrease in the amount of visceral fat (11.61 g less, P < 0.05) and in the size of adipose cells (28% smaller, P < 0.01). Besides, Epi was able to decrease insulin, leptin, and Homeostasis Model Assessment -Insulin Resistance (HOMA-IR) (P < 0.05), as well as triglycerides, when the experimental group was compared to the untreated male offspring of obese rats (P < 0.01)., Conclusions: Epi administration can reverse the negative effects that maternal obesity has on the male offspring. This could be because Epi reduces the amount of visceral fat and improves metabolic profile.

Hepatic sinusoidal obstruction syndrome (HSOS) is a rare liver disease with considerable morbidity and mortality. (-)-Epicatechin (EPI) is a natural flavonol. This study aims to investigate the protection of EPI against monocrotaline (MCT)-induced HSOS and its engaged mechanism. Results of serum alanine/aspartate aminotransferases (ALT/AST) activities, total bilirubin (TBil) and bile acids (TBA) amounts, liver histological evaluation, scanning electron microscope observation and hepatic metalloproteinase-9 (MMP-9) expression all demonstrated the protection by EPI against MCT-induced HSOS in rats. EPI attenuated liver oxidative injury induced by MCT. EPI enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of its downstream antioxidant genes in rats. Molecular docking results implied the potential interaction of EPI with the Nrf2 binding site in kelch-like ECH-associated protein-1 (Keap1). The EPI-provided protection against MCT-induced HSOS was diminished in Nrf2 knock-out mice when mice were treated with MCT for 24 h but not for 48 h. However, EPI reduced the increased liver myeloperoxidase (MPO) activity, hepatic infiltration of immune cells, pro-inflammatory cytokines expression and nuclear factor κB (NFκB) activation in both wild-type and Nrf2 knock-out mice when mice were treated with MCT for 48 h. EPI reduced the elevated serum heat shock protein 60 (HSP60) content, and reversed the decreased mitochondria expression of HSP60 and Lon in livers from MCT-treated rats. Furthermore, the MCT-induced HSOS was markedly alleviated in mice treated with anti-HSP60 antibody. Taken together, this study demonstrates that EPI attenuates MCT-induced HSOS by reducing liver oxidative injury via activating Nrf2 antioxidant pathway and inhibiting liver inflammatory injury through abrogating NFκB signaling pathway initiated by HSP60., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

As one of the important dietary antioxidants, (-)-epicatechin is a potent reactive oxygen species (ROS) scavenger involved in the redox modulation of the cell. When scavenging ROS, (-)-epicatechin will donate two electrons and become (-)-epicatechin quinone, and thus take over part of the oxidative potential of the ROS. The aim of the study is to determine where this chemical reactivity resides in (-)-epicatechin quinone. When this reactivity is spread out over the entire molecule, i.e. over the AC-ring and B-ring, this will lead to partial epimerization of (-)-epicatechin quinone to (-)-catechin quinone. In our experiments, (-)-epicatechin quinone was generated with tyrosinase. The formation of (-)-epicatechin quinone was confirmed by trapping with GSH, and identification of (-)-epicatechin-GSH adducts. Moreover, (-)-epicatechin quinone could be detected using Q-TOF/MS despite its short half-life. To detect the epimerization, the ability of ascorbate to reduce the unstable flavonoid quinones into the corresponding stable flavonoids was used. The results showed that the reduction of the formed (-)-epicatechin quinone by ascorbate did not result in the formation of an appreciable amount of (-)-catechin. Therefore it can be concluded that the chemical reactivity of (-)-epicatechin quinone mainly resides in its B-ring. This could be corroborated by quantum chemical calculations. Understanding the stabilization of the (-)-epicatechin quinone will help to differentiate between flavonoids and to select the appropriate compound for a specific disorder., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

This paper reviews pioneering human studies, their limitations and recent investigations on the absorption, metabolism, distribution and excretion (aka bioavailability) of (-)-epicatechin. Progress has been made possible by improvements in mass spectrometric detection when coupled to high performance liquid chromatography and through the increasing availability of authentic reference compounds of in vivo metabolites of (-)-epicatechin. Studies have shown that [2- 14 C](-)-epicatechin is absorbed in the small intestine with the 12 structural-related (-)-epicatechin metabolites (SREMs), mainly in the form of (-)-epicatechin-3'-O-glucuronide, 3'-O-methyl-(-)-epicatechin-5-sulfate and (-)-epicatechin-3'-sulfate, attaining sub-μmol/L peak plasma concentrations (C max ) ∼1 h after ingestion. SREMs were excreted in urine over a 24 h period in amounts corresponding to 20% of (-)-epicatechin intake. On reaching the colon the flavan-3-ol undergoes microbiota-mediated conversions yielding the 5C-ring fission metabolites (5C-RFMs) 5-(hydroxyphenyl)-γ-valerolactones and 5-(hydroxyphenyl)-γ-hydroxyvaleric acids which appear in plasma as phase II metabolites with a C max of 5.8 h after intake and are excreted in quantities equivalent to 42% of the ingested (-)-epicatechin. Other catabolites excreted in 0-24 h urine in amounts equivalent to 28% of intake included 3-(3'-hydroxyphenyl)hydracrylic acid, hippuric acid and 3'-hydroxyhippuric acid. Overall (-)-epicatechin is highly bioavailable with urinary excretion indicating that 95% is absorbed and passes through the circulatory systems as a diversity of phase II metabolites. Rats produce a very different profile of SREMs than that of humans. These findings demonstrate that ex vivo studies investigating the mechanisms underlying the protective effects of (-)-epicatechin on human health should make use of physiological concentrations human of SREMs and 5C-RFMs, and not the parent (-)-epicatechin, with model systems derived from human cells. In epidemiological studies 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-sulfate and 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-O-glucuronide, the principal 5C-RFMs in both plasma and urine, could serve as key biomarkers of (-)-epicatechin intake., (Copyright © 2017. Published by Elsevier Ltd.)

Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD) is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (-)-epicatechin (EC) supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ) were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2-20mg/kg body weight) mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα)-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption., (Copyright © 2017. Published by Elsevier B.V.)

We have reported on the capacity of (-)-epicatechin ((-)-EPI) to stimulate mitochondrial biogenesis (MiB) in mouse skeletal muscle (SkM). However, the mechanisms mediating the effects of (-)-EPI are not fully understood. We previously identified a role of the G-protein coupled estrogen receptor (GPER) in modulating the vascular effects of (-)-EPI. We therefore tested the hypothesis that GPER mediates (at least in part) the stimulatory effects of (-)-EPI on MiB in SkM cells. As an in vitro model, we employed mouse SkM-derived C2C12 myoblasts differentiated into myotubes. Using confocal microscopy, we detected GPER at the cell surface and cytoplasm in C2C12 myotubes. Treatment with (-)-EPI (3 and 10μM) resulted in the stimulation of MiB as per increases in mitochondrial inner (MitoTracker Red FM fluorescence staining) and outer membrane (porin protein levels) markers, transcription factors involved in MiB stimulation (i.e., nuclear respiratory factor-2 [NRF-2] and mitochondrial transcription factor A [TFAM] protein levels) and citrate synthase (CS) activity levels. (-)-EPI-treated myotubes were longer and wider compared to vehicle-treated myotubes. The effects of (-)-EPI on myotube mitochondria and cell size were larger in magnitude to those observed with the GPER agonist G-1. The chemical blockade and down-regulation (siRNA) of GPER evidenced a partial and complete blockade of measured endpoints following (-)-EPI- or G-1-treatment, respectively. Altogether, results indicate that GPER is expressed in muscle cells and appears to mediate to a significant extent, the stimulatory effects of (-)-EPI on MiB. Thus, GPER activation may account for the stimulatory effects of (-)-EPI on SkM structure/function., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In this study, we demonstrate that (-)-epicatechin (Epi), a cacao flavanol, induces the browning of fat by promoting mitochondrial biogenesis, enhancing indicators of mitochondrial structure and function, increasing fatty acid metabolism and upregulating the expression of brown adipose tissue-specific proteins in a high-fat diet mouse model of obesity and in cultured human adipocytes. Epi treatment significantly improved mitochondrial function, as measured by citrate synthase activity, and also reduced protein acetylation of total and specific regulators in both adipose tissue and human adipocytes. Browning of fat via Epi was evidenced by the increased expression of key thermogenic genes, phosphorylation of upstream regulators of fatty acid oxidation, and reduced triglyceride levels. Properly designed clinical trials are needed to explore the potential of Epi as an agent that promotes the browning of fat., (Copyright © 2017. Published by Elsevier B.V.)

Background: The Cotoneaster species are widely used as traditional purposes in different countries including Turkey., Purpose: The study was performed to evaluate the biological and chemical profile of two extracts (methanol (T-Me; F-Me) and water (T-W; F-W)) from two parts (twigs and fruits) of Cotoneaster integerrimus., Materials and Methods: Antioxidant (free radical scavenging (DPPH), reducing power (CUPRAC and FRAP), phosphomolybdenum and metal chelating), enzyme inhibitory (cholinesterase, tyrosinase, α-amylase and α-glucosidase), antimicrobial (standard microorganisms and methicillin-resistant Staphylococcus aureus isolates (MRSA)) and mutagenic/antimutagenic effects (by Ames assay) were tested for biological profile. For chemical profile, total and individual phenolic components were detected for each extract., Results: Generally, T-Me reflected the strongest biological effects with the highest level of phenolics (115. 15 mgGAEs/g extract). Also, twig extracts had more potent biological effects as compared to flower extracts. Eight-teen phenolics were identified in the extracts. (-)- epicatechin was the major constituent in all extracts and is mainly responsible for biological activities observed. Its amount present in F-W and T-W were 9.27 and 32.89mg/g extract, respectively. Also, molecular docking was used to understand enzyme-epicatechin interactions., Conclusion: From these results, this plant has a great potential as a health promoter for developing novel functional food ingredients and pharmaceutical preparations., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

(-)-Epicatechin increases indicators associated with mitochondrial biogenesis in endothelial cells and myocardium. We investigated endothelial nitric oxide synthase involvement on (-)-epicatechin-induced increases in indicators associated with mitochondrial biogenesis in human coronary artery endothelial cells cultured in normal-glucose and high-glucose media, as well as to restore indicators of cardiac mitochondria from the effects of simulated diabetes. Here, we demonstrate the role of endothelial nitric oxide synthase on (-)-epicatechin-induced increases in mitochondrial proteins, transcription factors and sirtuin 1 under normal-glucose conditions. In simulated diabetes endothelial nitric oxide synthase function, mitochondrial function-associated and biogenesis-associated indicators were adversely impacted by high glucose, effects that were reverted by (-)-epicatechin. As an animal model of type 2 diabetes, 2-month old C57BL/6 mice were fed a high-fat diet for 16 weeks. Fasting and fed blood glucose levels were increased and NO plasma levels decreased. High-fat-diet-fed mice myocardium revealed endothelial nitric oxide synthase dysfunction, reduced mitochondrial activity and markers of mitochondrial biogenesis. The administration of 1 mg/kg (-)-epicatechin for 15 days by oral gavage shifted these endpoints towards control mice values. Results suggest that endothelial nitric oxide synthase mediates (-)-epicatechin-induced increases of indicators associated with mitochondrial biogenesis in endothelial cells. (-)-Epicatechin also counteracts the negative effects that high glucose or simulated type 2 diabetes has on endothelial nitric oxide synthase function., Competing Interests: Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2016.)

Traumatic brain injury (TBI), which leads to disability, dysfunction, and even death, is a prominent health problem worldwide with no effective treatment. A brain-permeable flavonoid named (-)-epicatechin (EC) modulates redox/oxidative stress and has been shown to be beneficial for vascular and cognitive function in humans and for ischemic and hemorrhagic stroke in rodents. Here we examined whether EC is able to protect the brain against TBI-induced brain injury in mice and if so, whether it exerts neuroprotection by modulating the NF-E2-related factor (Nrf2) pathway. We used the controlled cortical impact model to mimic TBI. EC was administered orally at 3h after TBI and then every 24h for either 3 or 7 days. We evaluated lesion volume, brain edema, white matter injury, neurologic deficits, cognitive performance and emotion-like behaviors, neutrophil infiltration, reactive oxygen species (ROS), and a variety of injury-related protein markers. Nrf2 knockout mice were used to determine the role of the Nrf2 signaling pathway after EC treatment. In wild-type mice, EC significantly reduced lesion volume, edema, and cell death and improved neurologic function on days 3 and 28; cognitive performance and depression-like behaviors were also improved with EC administration. In addition, EC reduced white matter injury, heme oxygenase-1 expression, and ferric iron deposition after TBI. These changes were accompanied by attenuation of neutrophil infiltration and oxidative insults, reduced activity of matrix metalloproteinase 9, decreased Keap 1 expression, increased Nrf2 nuclear accumulation, and increased expression of superoxide dismutase 1 and quinone 1. However, EC did not significantly reduce lesion volume or improve neurologic deficits in Nrf2 knockout mice after TBI. Our results show that EC protects the TBI brain by activating the Nrf2 pathway, inhibiting heme oxygenase-1 protein expression, and reducing iron deposition. The latter two effects could represent an Nrf2-independent mechanism in this model of TBI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

High fructose consumption has been associated to deleterious metabolic conditions. In the kidney, high fructose causes renal alterations that contribute to the development of chronic kidney disease. Evidence suggests that dietary flavonoids have the ability to prevent/attenuate risk factors of chronic diseases. This work investigated the capacity of (-)-epicatechin to prevent the renal damage induced by high fructose consumption in rats. Male Sprague Dawley rats received 10% (w/v) fructose in the drinking water for 8 weeks, with or without supplementation with (-)-epicatechin (20mg/kg body weight/d) in the rat chow diet. Results showed that, in the presence of mild proteinuria, the renal cortex from fructose-fed rats exhibited fibrosis and decreases in nephrin, synaptopodin, and WT1, all indicators of podocyte function in association with: (i) increased markers of oxidative stress; (ii) modifications in the determinants of NO bioavailability, i.e., NO synthase (NOS) activity and expression; and (iii) development of a pro-inflammatory condition, manifested as NF-κB activation, and associated with high expression of TNFα, iNOS, and IL-6. Dietary supplementation with (-)-epicatechin prevented or ameliorated the adverse effects of high fructose consumption. These results suggest that (-)-epicatechin ingestion would benefit when renal alterations occur associated with inflammation or metabolic diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Among the K(+) channel blockers, 4-aminopyridine (4-AP) and margatoxin, blockers of voltage-gated K(+) (KV) channels, and glibenclamide, a selective ATP-sensitive K(+) (KATP) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca(2+)-activated K(+) channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80mM K(+), (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca(2+)-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium-independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and margatoxin-sensitive KV channels, as well as BKCa and KATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca(2+), interfere with intracellular Ca(2+) release and re-uptake by the sarcoplasmic reticulum., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD) is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (-)-epicatechin (EC) supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ) were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2-20mg/kg body weight) mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα)-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption.

Obesity and type 2 diabetes (T2D) are major public health concerns. Visceral adipose tissue inflammation is considered a significant contributor to obesity-associated T2D development. We previously showed that the flavan-3-ol (-)-epicatechin (EC) can mitigate insulin resistance in mice fed a high fat diet (HFD). This study investigated the capacity of EC to inhibit visceral adipose tissue inflammation occurring as a consequence of HFD consumption in C57BL/6J mice, and characterized the underlying mechanisms. In association with the development of obesity and insulin resistance, HFD consumption caused inflammation in the visceral adipose tissue as evidenced by activation of the pro-inflammatory transcription factor NF-κB and increased tissue levels of the macrophage marker F4/80, tumor necrosis factor alpha (TNFα), and the chemokine MCP-1. EC supplementation mitigated all these events. In addition, we observed activation of the three branches of the unfolded protein response (UPR), and upregulation of NADPH oxidases NOX4 and NOX2 in visceral fat of mice fed HFD. These can account, at least in part, for the associated oxidative stress and activation of the redox sensitive NF-κB. Notably, EC supplementation mitigated this and the release of pro-inflammatory proteins from metabolically stressed adipocytes. Attenuation of adipocyte endoplasmic reticulum (ER) and oxidative stress by EC could contribute to decreased inflammation and improved visceral adipose tissue insulin sensitivity. Our results support the concept that consumption of EC-rich foods could mitigate obesity-associated insulin resistance through attenuation of adipose tissue inflammation.

[Display omitted] • GO/TiS 2 nanocomposites were synthesized and functionalized with Laccase. • Prepared nanocomposites with enzyme were used to modify screen-printed carbon electrodes to detect (-)-epicatechin. • The detection limit and the sensitivity of the biosensor were 0.073 μM and 0.3264 µ A.mM−cm−2, respectively. • This laccase based biosensor was succesfully used to determine (-)-epicatechin in wine and fruit juice. In this study, 2-dimensional graphene oxide-titanium disulfide (GO/TiS 2) nanolayers were synthesized, and the surface and size properties of nanolayers were investigated by transmission electron microscopy (TEM) technique. The nanolayers were used to modify the screen-printed electrode surface and applied as a micro-medium for Trametes versicolor laccase. The ability of this enzyme biosensor to detect the (-)-epicatechin has been demonstrated with a wide linear range (0.1–250 µM), LOD (0.073 µM), and sensitivity (0.3264 µ A µM−cm−2). In addition, the biosensor exhibited excellent selectivity allowing selective detection of (-)-epicatechin in the presence of other polyphenolic compounds and high reducing currents sensitivity (vs Ag/AgCl) examined at −0.6 V. The proposed biosensor showed reproducibility, reusability, long-term storage stability, and applicability in actual food samples with recovery values close to 100 %. Also, K m app and I max values ​​of the biosensor were determined as 2.245 µM and 0.757 µA, respectively. [ABSTRACT FROM AUTHOR]

Toona sinensis timbers are generally used in the furniture and building material in Indonesia, due to their reputed durability. The aim of this study was to identify the potential compounds responsible for the antitermite activity of T. sinensis against Coptotermes curvignathus. The methanol extracts of stem wood and stem bark of T. sinensis showed termiticidal activity. Our phytochemical investigated have been isolated two flavonoid compounds (+)-catechin (1) and its dimer procyanidin B3 (2) and one steroid compound β-sitosterol-D- glucoside (3) by bioassay-guided from Toona sinensis stem bark and tested them to antitermite activity by the no-choice test. In addition, we investigated the antitermite activity of (-)-epicatechin, (-)-epicatechin gallate and (-)-epigallocatechin gallate together with the isolated compounds in laboratory scale at a dose of 0.8% w/w. The results showed that (+)-catechin had the highest antifeedant and termiticidal activity after 21 days exposure to all other compounds tested, but no significant difference in mortality to its dimer procyanidin B3, diastereoisomer (-)-epicatechin and galloylated catechin (-)-epigallocatechin gallate on statistical analysis. [ABSTRACT FROM AUTHOR]

Background: Maternal nutritional status can impact numerous early developmental processes. In certain cases, these effects can influence the risk their offspring can have for select chronic diseases later in life. Consequently, in this article we report on the effects of maternal consumption of high levels of certain flavonoids on the development of coronary artery disease (CAD) in an atherosclerosis-prone mutant mouse model. Methods: LDLr -/- mutant mice were fed a control fat (CF), high fat (HF), or the HF diet supplemented with epicatechin and catechin (HFEC) or rutin (HFRU), prior to pregnancy and during lactation, in order to explore whether the flavonoids influenced markers of vascular health in the lactating dams (lactation day (LD) 21). Post-weaning (postnatal day (PND) 22), offspring were challenged with an atherogenic environment (HF diet in the absence of flavonoids) and vascular health markers were assessed in the adult offspring (PND 60). Results: Dams fed the HF diet had elevated markers of atherosclerosis on LD 21 when compared to the dams fed with the control diet. Flavonoid consumption prior to pregnancy and during lactation had inconsistent effects on maternal markers of atherosclerosis (plasma cholesterol, aortic lipid accumulation, and oxidative stress biomarkers) at LD 21 compared to dams fed the HF diet without flavonoids. At PND 60, there were no differences in vascular health markers among the groups of LDLr -/- offspring whose mothers consumed the CF or the HF diet with or without flavonoids during lactation. Conclusions: Maternal consumption of the flavonoid-supplemented HF diets had modest effects on maternal markers of atherosclerosis. The exposure of offspring to the flavonoid-supplemented HF diets during early lactation had little effect on the cardiovascular parameters assessed in the adult offspring. [ABSTRACT FROM AUTHOR]

Pale catechu, a well-known crude drug, has been widely used for anti-diarrhea. Due to its medicinal usage, this study was performed to evaluate the pharmacognostic and antioxidant properties as well as catechins contents of pale catechu in Thailand. Twenty samples of pale catechu collected from traditional drug stores throughout Thailand were investigated. Antioxidant activities, total phenolic, nontannin phenolic, and total tannin contents were evaluated. (+)-catechin and (-)-epicatechin were quantitatively analyzed by high performance liquid chromatography. The results revealed that most of pale catechu samples were adulterated according to high ash values. Qualified pale catechu in Thailand were demonstrated for their average contents of total ash, acid insoluble ash, loss on drying, and moisture as 5.20 ± 0.19, 1.61 ± 0.17, 13.14 ± 0.10, and 13.20 ± 1.07 g/100 g of dry weight, respectively. The ethanol and water soluble extractive matters were 91.66 ± 5.16 and 44.59 ± 3.18 g/100 g of dry weight respectively. (+)-catechin in theses samples was 478.87 ± 2.77 µg/mg of crude drug, whereas (-)-epicatechin was found to be trace (

Background: According to Thai traditional medicine, Pentace burmanica Kurz. stem bark has been used as crude drug for treating diarrhea. However, the crude drug is also found susceptible to adulteration. Objectives: To develop specific standardization parameters of P. burmanica stem bark in Thailand and to determine the (+)-catechin and (-)-epicatechin contents of P. burmanica stem bark by HPLC analysis. Materials and Methods: P. burmanica stem barks from various sources throughout Thailand were investigated according to WHO guideline of the pharmacognostic specification. High performance liquid chromatography (HPLC) was performed for (+)-catechin and (-)-epicatechin quantification. Results: Macroscopic evaluation was demonstrated as whole plant drawing. Microscopic evaluation of stem bark powdered drug showed fragment of fibers, resin masses, tannin masses, starch grain, calcium oxalate, and fragment of parenchyma. Physico-chemical parameters revealed that total ash, acid insoluble ash, loss on drying, and water content should be not more than 3.58, 0.50, 8.40, and 9.70% of dry weight respectively; while ethanol and water soluble extractive values should not be less than 21.90 and 19.06% of dry weight respectively. Both (+)-catechin and (-)-epicatechin were existed in P. burmanica ethanolic extract. Owing to the small amount of (+)-catechin, quantitation of its content was omitted. However, (-)-epicatechin contents was found as 59.74 ± 1.69μg/mg of crude extract. Conclusion: The pharmacognostic investigations can be used to set the standard parameters of P. burmanica stem bark in Thailand. HPLC method can be applied to determine (+)-catechin and (-)-epicatechin content in plant materials. [ABSTRACT FROM AUTHOR]

The main polyphenols in callus and cell suspension cultures of Taxus cuspidata and T. baccata were (+)-catechin and (−)-epicatechin, while lignans, such as (+)-taxiresinol, (+)-isotaxiresinol, (+)-isolariciresinol and (−)-secoisolariciresinol, were present in trace amounts. T. cuspidata cells contained 1.7% (+)-catechin and 2.4% (−)-epicatechin on dry wt basis but when stimulated with methyl jasmonate produced 3.4% catechin and 5.2% epicatechin. These are the highest levels of these metabolites obtained in plant cell cultures. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the protective effect of (+)-catechin and (−)-epicatechin against 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]-quinoxaline (4,8-diMeIQx) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP)-induced DNA damage in human hepatoma cells (HepG2). DNA damage (strand breaks and oxidized purines/pyrimidines) was evaluated by the alkaline single-cell gel electrophoresis or comet assay. Increasing concentrations of 8-MeIQx, 4,8-diMeIQx and PhIP induced a significant increase in DNA strand breaks and oxidized purines and pyrimidines in a dose-dependent manner. Among those, PhIP (300 µ m) exerted the highest genotoxicity. (+)-Catechin exerted protection against oxidized purines induced by 8-MeIQx, 4,8-diMeIQx and PhIP. Oxidized pyrimidines and DNA strand breaks induced by PhIP were also prevented by (+)-catechin. Otherwise, (−)-epicatechin protected against the oxidized pyrimidines induced by PhIP and the oxidized purines induced by 8-MeIQx and 4,8-diMeIQx. One feasible mechanism by which (+)-catechin and (−)-epicatechin exert their protective effect towards heterocyclic amines-induced oxidative DNA damage may be by modulation of phase I and II enzyme activities. The ethoxyresorufin O-deethylation (CYP1A1) activity was moderately inhibited by (+)-catechin, while little effect was observed by (−)-epicatechin. However, (+)-catechin showed the greatest increase in UDP-glucuronyltransferase activity. In conclusion, our results clearly indicate that (+)-catechin was more efficient than (−)-epicatechin in preventing DNA damage (strand breaks and oxidized purines/pyrimidines) induced by PhIP than that induced by 8-MeIQx and 4,8-diMeIQx. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Isoflavonoids (−)-medicarpin, (−)-vestitol, formononetin, 8-hydroxydaidzein, and 6″- O-acetylononin were isolated for the first time in addition to (−)-catechin, (−)-epicatechin, protocatechoic acid, raspberry ketone, and rhododendrol from the alcohol extract of Hedysarum theinum roots. [ABSTRACT FROM AUTHOR]

A high performance liquid chromatographic (HPLC) method, with fluorometric detection, was developed for studying the oral absorption and ensuing plasma pharmacokinetics of (+)‐catechin and (-)‐epicatechin in a small animal model. A plasma sample was first incubated with buffered β‐glucuronidase plus sulfatase to release the catechins from their conjugated forms, and next deproteinized with methanol‐perchloric acid (3+2) mixture containing an internal standard ((+)‐catechin for the assay of (-)‐epicatechin and the latter for the assay of the former). Analyses were carried out on a Microsorb‐MV C18 column, with methanol‐water‐formic acid (15&ratio;84&ratio;1) flowing at 1 mL/min, and a fluorometric detector set at an excitation wavelength of 280 nm and an emission wavelength of 310 nm. (+)‐Catechin and (-)‐epicatechin eluted at 6.7 min and 13.8 min, respectively. Detector responses were linearly related to concentrations of catechin compound in the range 5–160 nM (r 2 ≥0.993). The limits of detection were 0.75 nM for (+)‐catechin and 1.5 nM for (-)‐epicatechin. Accuracy and precision were evaluated at three concentrations of each catechin compound. Recoveries of (+)‐catechin and (-)‐epicatechin from spiked rat plasma ranged from 95.0 to 101.8% and from 98.7 to 102.5%, respectively. The RSD values for interday variability were in the range 1.27–4.07% for (+)‐catechin and 0.47–2.04% for (-)‐epicatechin. The method was suitable for assessing the plasma pharmacokinetics of (+)‐catechin and (-)‐epicatechin in rats after their individual oral administration as solutions in either water or milk. [ABSTRACT FROM AUTHOR]

Background/Aims: (+)-Catechin and (–)-epicatechin are considered as disease preventive flavan-3-ols of foods like fruits, beverages and chocolate. We investigated mechanisms and kinetics of (+)-catechin and (–)-epicatechin uptake employing a validated in vitro model with isolated pig brush border membrane vesicles. Methods: Vesicles were isolated from pig small intestine employing the divalent cation method. Characterization (marker enzymes, electron microscopy) confirmed their purity and function. Transport studies with (+)-catechin and (–)-epicatechin under predefined conditions [presence/absence of sodium, pH gradient, temperature (8–37°C), various initial substrate concentrations (2–20 mmol/l)] revealed a measurable transport (HPLC analyses) across the brush border membrane for both substrates. Re sults: Catechin transport was stimulated by an outwardly directed H+ gradient (pHi 5.5/pHo 7.5). The presence of an inwardly directed Na+ gradient did not result in a transient overshoot in (+)-catechin and (–)-epicatechin uptake. At 37°C, subtraction of diffusion from the total transport rate showed saturation kinetics. Conclusion: Our in vitro study indicate that both (+)-catechin and (–)-epicatechin are transported across the basolateral membrane using a dual transport system consisting of free diffusion (dominant at low concentrations) and carrier-mediated facilitated diffusion. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Tea polyphenols, including (+)-catechin, (-)-epicatechin, and (-)-epigallocatechin-3-gallate (EGCG), have been shown to possess potent antioxidant and anticancer activities. The aim of this study was to evaluate the possibility of using liposomes for the local delivery, including skin and tumor deposition, of these polyphenols. Liposomes containing egg phosphatidylcholine, cholesterol, or anionic species were prepared by a solvent evaporation method and then were subjected to a probe sonicator. The size, zeta potential and entrapment efficiency of these liposomal formulations were determined to provide correlations with results from a subsequent in vivo study. The release rate study showed that inclusion of an anionic species, such as deoxycholic acid (DA) or dicetyl phosphate (DP), increased the permeability of the lipid bilayers, leading to the rapid release of these formulations. No significant increase in skin deposition of catechins was observed after topical application of liposomes. On the other hand, a greater amount of catechins were delivered into the solid tumor by liposomes than by the aqueous solution. The drug release rate and vesicle size of liposomes may influence drug deposition in tumor tissues. The isomers, (+)-catechin and (-)-epicatechin, showed different physicochemical properties in liposomes and for local deposition in the skin and tumor. Finally, the presence of gallic acid ester in the structure of EGCG significantly increased the tissue uptake of catechins. [ABSTRACT FROM AUTHOR]