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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. [ABSTRACT FROM AUTHOR]

Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is becoming more prominent globally due to an increase in the prevalence of obesity, dyslipidemia, and type 2 diabetes. A great deal of studies have proposed potential treatments for MASLD, with few of them demonstrating promising results. The aim of this study was to investigate the potential effects of (-)-epicatechin (EPI) on the development of MASLD in an in vitro model using the HepG2 cell line by determining the metabolic viability of the cells and the levels of PPARα, PPARγ, and GSH. HepG2 cells were pretreated with 10, 30, 50, and 100 μM EPI for 4 h to assess the potential effects of EPI on lipid metabolism. A MASLD cell culture model was established using HepG2 hepatocytes which were exposed to 1.5 mM oleic acid (OA) for 24 h. Moreover, colorimetric MTS assay was used in order to determine the metabolic viability of the cells, PPARα and PPARγ protein levels were determined using enzyme-linked immunosorbent assay (ELISA), and lipid accumulation was visualized using the Oil Red O Staining method. Also, the levels of intracellular glutathione (GSH) were measured to determine the level of oxidative stress. EPI was shown to increase the metabolic viability of the cells treated with OA. The metabolic viability of HepG2 cells, after 24 h incubation with OA, was significantly decreased, with a metabolic viability of 71%, compared to the cells pretreated with EPI, where the metabolic viability was 74–86% with respect to the concentration of EPI used in the experiment. Furthermore, the levels of PPARα, PPARγ, and GSH exhibited a decrease in response to increasing EPI concentrations. Pretreatment with EPI has demonstrated a great effect on the levels of PPARα, PPARγ, and GSH in vitro. Therefore, considering that EPI mediates lipid metabolism in MASLD, it should be considered a promising hepatoprotective agent in future research.

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. [ABSTRACT FROM AUTHOR]

(-)-Epicatechin (EC), a primary form of flavan-3ol and a building block of proanthocyanidins, has health benefits as it is a potent antioxidant. So far, no quantitative trait loci (QTLs) associated with EC have yet been identified in soybean. In this study, QTLs for EC and hilum color were identified in recombinant inbred lines (RILs) derived from the varieties Jinpung and IT109098 using high-resolution single nucleotide polymorphism linkage mapping. This revealed two major QTLs for EC content, qEC06 and qEC08. qEC06 spanned the Tawny (T) locus encoding flavonoid 3′-hydroxylase. qEC08, located near the Inhibitor (I) locus on Chr08, was also a major QTL for hilum color; however, allelic stacking of qEC08 and I revealed no relationship between I and EC content. RILs with IT109098 alleles at both qEC06 and qEC08 had higher EC content than other lines. These results will enable the production of soybean varieties with high EC content via marker-assisted selection. [ABSTRACT FROM AUTHOR]

Green tea extract (GTE) is a supplement derived from the green tea plant which aids in weight loss along with other innumerable health. New analytical methods for determining GTE via its catechins using a design-assisted spectrophotometric methodologies are provided. The procedures are based on the formation of orange-colored products that are detectable at 473 or 455 nm, respectively, when catechins react with MBTH in the presence of FeCl3 (method I) or K2S2O8 (method II). Critical parameters were optimized using design of experiments (DOE). The absorbance-concentration plots were rectilinear over the ranges 4.0–20.0 or 4.0–40.0 µg cm−3 with limits of detection 0.393 or 0.493 µg cm−3 for methods I & II, respectively. Our methods were applied to pure catechins in GTE, namely (-)-epicatechin and (-)-epigallocatechin gallate. Moreover, the proposed methods were perfectly applied to the analysis of GTE in a commercial tablet. Good agreement between the collected data and those of the reported approach demonstrating that there were no significant variations. According to International Council for Harmonization (ICH) Guidelines, the procedures were validated. [ABSTRACT FROM AUTHOR]

For this study, procyanidins generated through the autoxidation of (-)-epicatechin (Flavan-3-ol) under mildly acidic conditions (pH = 6.0) were characterized with ultra high-performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS/MS). Two procyanidins (types A and B) and a mix of oligomers were generated through the autoxidation of (-)-epicatechin. The antiproliferative activity of this mixture of procyanidins on MDA-MB-231, MDA-MB-436, and MCF-7 breast cancer cells was evaluated. The results indicate that the procyanidin mixture inhibited the proliferation of breast cancer cells, where the activity of the procyanidin mixture was stronger than that of (-)-epicatechin. Moreover, the mechanism underlying the antiproliferative activity of procyanidins was investigated. The resulting data demonstrate that the procyanidins induced apoptotic cell death in a manner selective to cancerous cells. In particular, they caused the activation of intrinsic and extrinsic apoptotic pathways in the breast cancer cells. The findings obtained in this study demonstrate that the generation of procyanidins in vitro by the autoxidation of (-)-epicatechin has potential for the development of anti-breast cancer agents. [ABSTRACT FROM AUTHOR]

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 IC50 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. [ABSTRACT FROM AUTHOR]

BackgroundGenerated 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.ObjectivesWe evaluated the effects of (-)-epicatechin (EC) and different anthocyanins (ACs) and AC metabolites on GLP-1 metabolism in mice and on GLUTag cells.MethodsWe 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.ResultsLong-term supplementation with EC or AC increased mouse GLP-1 plasma concentrations (55% and 98%, respectively; P

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G protein estrogen receptor (GPER) has been implicated in oestrogen-signalling routes in several biological systems and has been associated with different pathophysiological processes. So, there has been an increasing interest in identifying GPER-binding small molecules to modulate their biological activity. To this aim, we report the ligand-based virtual screening of GPER-binding molecules based on chemical similarity to (-)-epicatechin (flavanol reported as a ligand for the GPER receptor). Further structure-based screening allowed us to identify molecules with higher binding affinity to GPER based on molecular docking, molecular dynamic simulation and adaptative biasing force calculations. Here, we predicted 4 small molecules with a high ability to bind GPER exhibit favourable energy interaction. [ABSTRACT FROM AUTHOR]

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.

(-)-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. [ABSTRACT FROM AUTHOR]

This study evaluated the anti-inflammatory effect of epicatechin (EC) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) of tracheal installation in BALB/c mice. It was observed that EC could alleviate not only the histopathological changes but also decrease the wet/dry weight (W/D) ratio of lung tissues. It also suppressed the release of IL-1β, IL-6, and TNF-α in serum, bronchoalveolar lavage fluid (BALF), and lung tissues, respectively. A quantitative realtime PCR-based study further indicated that EC also inhibited the levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA in lung tissues. In addition, the Western blot report suggested that EC was closely involved in the inhibition of phosphorylation of ERK, JNK, p38, p65, and IκB in mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathway. These results provide an experimental and theoretical basis for treating pulmonary inflammation by EC. [ABSTRACT FROM AUTHOR]

(-)-Epicatechin (EC) is one of the most popular polyphenols present in various food products in daily life. Upon intake, it is intensively metabolized by microbiota in the large intestine. In the present study, intra- and inter-individual variations in this gut microbial conversion of EC and the concomitant formation of its major metabolites, including 5-(3′,4′-dihydroxy phenyl)-γ-valerolactone (3,4-diHPV), were identified and quantified via liquid chromatography triple quadrupole mass spectrometry (LC-TQ-MS) in anaerobic fecal incubations. In addition, the bioactivity of EC and 3,4-diHPV in activating Nrf2-mediated gene expression was tested quantifying their effects in the U2OS Nrf2 CALUX assay (a reporter gene assay that is used to test the potency of chemicals in activation of Nrf2 signaling), and on the expression levels of Nrf2-related proteins in Hepa1c1c7 and Caco-2 cells via nanoLC-MSMS. A quantitative real-time polymerase chain reaction (RT-qPCR) was carried out to confirm selected Nrf2-regulated gene expressions at the mRNA level. Results obtained show that both intra- and inter-individual differences exist in human gut microbial EC degradation and 3,4-diHPV formation, with inter-individual differences being more distinct than intra-individual differences. The metabolite, 3,4-diHPV, showed higher potency in the U2OS Nrf2 CALUX assay than EC itself. Among the obviously altered Nrf2-related proteins, 14 and 10 Nrf2-associated proteins were upregulated to a higher extent upon 3,4-diHPV treatment than in the EC treated group for Hepa1c1c7 and Caco-2 cells, respectively. While only three and four of these Nrf2-associated proteins were induced at a higher level upon EC than upon 3,4-diHPV treatment for Hepa1c1c7 and Caco-2 cells, respectively. RT-qPCR results showed that indeed Nrf2-mediated genes (e.g., Nqo1 and Ugt1a) were only induced significantly in 3,4-diHPV treated and not in EC treated Hepa1c1c7 cells. Taken together, the results suggest that the major colonic EC metabolite, 3,4-diHPV, was more capable of inducing Nrf2-mediated gene expression than its parent compound EC. This implies that the evident inter- and intra-individual differences in the microbial conversion of EC to this major metabolite 3,4-diHPV may affect the overall health-promoting effects of EC consumption related to the Nrf2 pathway activation.

Oxidative stress, mitochondrial impairment, and pathological amyloid beta (Aβ) deposition are involved in the pathogenesis of dry age-related macular degeneration (AMD). The natural flavonoid (–)-epicatechin (EC) is known to be an antioxidant and neuroprotective compound. Whether EC plays a therapeutic role in AMD is unknown. In this work, we aimed to assess the efficacy and molecular mechanisms of EC against sodium iodate (NaIO3)-induced retinal degeneration in C57BL/6 mice via bioinformatic, morphological, and functional methods. We demonstrated that EC had no toxic effects on the retina and could ameliorate retinal deformation and thinning. EC treatment prevented outer retinal degeneration, reduced drusen-like deposits, increased b-wave amplitude in electroretinography, blocked retinal gliosis, and increased the number and quality of mitochondria. Importantly, EC increased the protein expression of OPA1 and decreased the expression of PINK1, indicating the role of EC in mitochondrial fusion that impaired by NaIO3. Moreover, EC downregulated APP and TMEM97 levels, upregulated PGRMC1 levels, and reduced subretinal Aβ accumulation. This study illustrated that EC, which may become a promising therapeutic strategy for AMD, prevented NaIO3-induced retinal degeneration, and this improvement may be associated with the mitochondrial quality control and the TMEM97/PGRMC1/Aβ signaling pathway.

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.

High-performance thin-layer chromatography‒mass spectrometry (HPTLC‒MS) method was developed for the estimation of epimers (+)-catechin (CA) and (‒)-epicatechin (ECA) in Onosma bracteatum Wall. Resolving these epimers is challenging and so method optimization was done for the selection of the stationary phase and the mobile phase to achieve their coherent separation. To further increase the reliability of the obtained densitometric results, HPTLC–MS analysis was performed. The genus Onosma L. is a species-rich genus that exhibits complex patterns of morphological and karyological diversity, and highly debatable taxonomic approaches. Thus, many similar species are described based on morphological differences and often quite ambiguous. To facilitate the identification of O. bracteatum, separation was achieved using pre-coated silica gel 60 F254 HPTLC plate as the stationary phase and a mixture of diisopropyl ether–ethyl acetate–formic acid (9.0:0.2:0.7, V/V) as the mobile phase for the separation of epimers CA and ECA. Sample preparation, mobile phase selection and optimization were given importance to manage good resolution (RF) of these markers. Flavan-3-ols CA and ECA were identified and confirmed on the basis of RF and in situ UV and MS overlaid spectra with respective standards. The method was validated for linearity, inter-day precision, intra-day precision, repeatability, accuracy, specificity, limit of detection, and limit of quantification. The average recoveries for epimers CA and ECA from ethyl acetate extract fraction (MEF) were found 98.86 and 99.03% indicating the good reproducibility for each marker. The proposed validated HPTLC method is simple, accurate and reproducible and is the first report on the separation and quantification of the epimers CA and ECA in O. bracteatum using HPTLC–MS. [ABSTRACT FROM AUTHOR]

In this study, (-)epicatechin (EC) and β-glucan (BG) were identified as the active compounds in highland barley grain that modulated glucose metabolism. The mechanism underlying EC may target on insulin receptor and regulate target on insulin receptor substrate-1 /phosphatidylinositol 3-kinase / protein kinase B (Akt) pathway, and BG may target on mammalian rapamycin receptor and regulate the Akt pathway. EC and BG showed anti-hyperglycemic effects and modulated hepatic glucose metabolism in mice with impaired glucose tolerance. Moreover, EC combined with BG showed synergistic effects on the Akt pathway, thereby improved glucose uptake through up-regulating glucose transporter 4, improved glycogen synthesis by down-regulating glycogen synthase kinase-3β, and inhibiting gluconeogenesis by down-regulating phosphoenolpyruvate carboxykinase 1 protein expression. These results provide evidence of a whole highland barley grain diet to prevent type 2 diabetes or developing EC and BG as new dietary supplement.

Dietary constituents of plants such as flavonoids are very important in ameliorating the challenges of metabolic disorders such as diabetes mellitus. The study evaluated the antidiabetic activities of fractions and a known flavonoid isolated from Gnetum africanum (Welw) of fasting blood sugar (FBS) in alloxan-induced diabetic albino rats. Antidiabetic activity-guided isolation by column chromatographic (CC) separation of methanol extract and purification of the most active CC fractions by semi-preparative high performance liquid chromatograpgy (HPLC) yielded a known flavonoid (GAF7.4) and four other uncharacterized fractions. The structure of GAF7.4 was elucidated based on the 1D and 2D NMR and HREIMS spectroscopic analyses. Antidiabetic activity was conducted by alloxan-induced FBS in diabetic rats model using glibenclamide as standard. The flavonoid (GAF7.4) was identified as (-)-epicatechin. The CC fraction 7 (50 mg/kg) elicited significant (p < 0.05) reduction in FBS of 42.3 % after 6 h. The isolated flavonoid (GAF7.4), 10 mg/kg dose caused a significantly higher reduction in FBS of 71.4 % in alloxan induced diabetic rats compared with 41.2 % reduction in glibenclamide (2 mg/kg) control. This represented the first report of epicatechin in G. africanum and our findings have contributed new knowledge to antidiabetic constitutents of the plants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• (‒)-Epicatechin revealed amoebicidal activity against Acanthamoeba trophozoites without cytotoxicity to mammalian cells • (‒)-Epicatechin induced death of Acanthamoeba castellanii via apoptosis-like programmed cell death and autophagic cell death pathways • (‒)-Epicatechin could be a candidate drug or supplemental compound for treating Acanthamoeba infections 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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

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.

The bark of Aesculus hippocastanum is an herbal remedy used in conditions connected with vascular insufficiency; however, there is a lack of data concerning its mechanisms of action. The present work is a preliminary investigation into some of the potential directions of the bark activity. The phytochemically (qualitative UHPLC-PDA-MS/MS and quantitative UHPLC-PDA assays) characterized extract and its four main constituents (esculin, fraxin, (‒)-epicatechin and procyanidin A2) were first evaluated in terms of their antioxidant capacity. All analytes demonstrated dose-dependent scavenging potential towards the most common in vivo oxidants, with particularly advantageous capacity of the extract and its flavan-3-ol constituents against peroxynitrite (3.37–13.26 mmol AA/g), hydroxyl radical (5.03–8.91 mmol AA/g) and superoxide radical (3.50–5.50 mmol AA/g). Moreover, even at low concentrations (1–5 µg/mL), they protected components of human plasma against oxidative damage inflicted by peroxynitrite, preventing oxidation of plasma protein thiols and diminishing the tyrosine nitration and lipid peroxidation. High efficiency of the analytes was also demonstrated in preventing the peroxynitrite-induced nitrative changes of fibrinogen (up to 80% inhibition for (‒)-epicatechin at 50 µg/mL), an important protein of coagulation cascade. Additionally, the extract and its constituents had, at most, moderate inhibitory activity towards platelet aggregation induced by ADP and only negligible influence on clotting times. The results show that, among the investigated properties, the antioxidant activity might, to the highest extent, be responsible for the bark efficacy in vascular disorders, thus supporting its application in those conditions; they also indicate the directions for future research that would allow for better understanding of the bark activity.

Numerous naturally occurring molecules have been studied for their beneficial health effects. Many compounds have received considerable attention for their potential medical uses. Among them, several substances have been found to improve mitochondrial function. This review focuses on resveratrol, (–)-epicatechin, and betaine and summarizes the published data pertaining to their effects on cytochrome c oxidase (COX) which is the terminal enzyme of the mitochondrial electron transport chain and is considered to play an important role in the regulation of mitochondrial respiration. In a variety of experimental model systems, these compounds have been shown to improve mitochondrial biogenesis in addition to increased COX amount and/or its enzymatic activity. Given that they are inexpensive, safe in a wide range of concentrations, and effectively improve mitochondrial and COX function, these compounds could be attractive enough for possible therapeutic or health improvement strategies.

Highlights • Kiwifruit leaf extracts inhibited the test plant growth in a dose dependent manner. • The kiwifruit roots were more sensitive to the leaf extracts than the hypocotyls. • (-)-Epicatechin was identified as a phytotoxic substance in kiwifruit leaves. • (-)-Epicatechin inhibited seedling growth of kiwifruit in a dose dependent manner. Abstract When aged kiwifruit (Actinidia deliciosa (A. Chev.) C.F. Liang et A.R. Ferguson) plants are replaced with young ones, the growth and productivity of the young plants were occasionally lower than expected. This symptom is typical of the replant problems reported in several fruit trees. Phytotoxic substances released from the plant are assumed to be involved in the replant problems. Although some substances contained in kiwifruit leaves have been reported to have phytotoxic activity, little is known about phytotoxicity and phytotoxic substances in kiwifruit leaves on the growth of the kiwifruit itself. Therefore, this study determined the phytotoxic activity of kiwifruit leaf extracts and soil extracts and identified a phytotoxic substance in kiwifruit leaves. Extracts of kiwifruit leaves inhibited the growth of Lepidium sativum , Lactuca sativa , Medicago sativa , Phleum pratense , Lolium multiflorum , Echinochloa crus-galli , and kiwifruit seedlings. The soil extracts also inhibited the growth of L. sativum. These results suggest that kiwifruit leaf extracts and soil extracts may possess phytotoxic substances. (-)-Epicatechin was isolated from the extracts with bioassay-guided separations using chromatography. The concentrations of (-)-epicatechin required for 50% growth inhibition of the hypocotyls and radicles of L. sativum were 27.9 and 10.7 mM, respectively, and those for the hypocotyls and radicles of kiwifruit were 13.9 and 7.6 mM, respectively. This substance may contribute to the phytotoxic activity of kiwifruit leaf extracts and may be involved in the kiwifruit replant problem. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Regular cocoa consumption has been shown to reduce blood pressure, improve lipid profiles, and increase insulin sensitivity and flow-mediated dilatation in healthy adults. It is assumed that these effects can be attributed to polyphenolic cocoa ingredients such as flavanols, especially to (--)-epicatechin.Nutritive intervention studies to prove this hypothesis are scarce. Objective: We aimed to evaluate whether regular consumption of 25 mg of pure (--)-epicatechin can affect increased cardiometabolic risk factors [blood pressure, glucose and lipid metabolism, lowdensity lipoprotein (LDL) oxidation] in overweight-to-obese subjects. Design: Forty-eight overweight or obese nonsmokers [body mass index (kg/m²) ≥25.0, ages 20--65 y] with clear signs of metabolic syndrome (blood pressure ≥130/85 mm Hg, glucose >5.55 mmol/L, or triglycerides >1.69 mmol/L or cholesterol >5.2 mmol/L in fasting blood) and without chronic diseases were included in a randomized, placebo-controlled, double-blind crossover study. Participants ingested daily 25 mg (--)-epicatechin (encapsulated) or placebo for 2-wk in random order (2-wk washout). After an overnight fast, blood pressure was monitored and blood samples were collected before and after both treatments. Anthropometric data were determined at each visit. Dietary intake was assessed by 3-d food records during both treatments and during run-in and washout phase. Results: Supplementation of pure (--)-epicatechin did not signifi- cantly affect blood pressure, glucose, insulin, homeostasis model assessment of insulin resistance, triglycerides, or total, LDL, or HDL cholesterol. Oxidized LDL, vitamins C and E, and β-carotene in plasma were not modulated. Body weight, fat mass, fat distribution, and the intake of energy, nutrients, and (--)-epicatechin from food remained stable throughout the study. Conclusions: Daily intake of 25 mg of pure (--)-epicatechin for 2 wk does not reduce cardiometabolic risk factors in overweight-to-obese adults. Thus, the hypothesis that the cardioprotective effects of regular cocoa consumption are exclusively ascribed to (--)-epicatechin should be reconsidered. The study was registered at the German Clinical Trial Register as DRKS-ID: DRKS00009846. [ABSTRACT FROM AUTHOR]

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 10 μM) 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. [ABSTRACT FROM AUTHOR]

A flavonoid, (-)-epicatechi (Epi), enhances long-term memory (LTM) formation in Lymnaea and reverses memory obstruction caused by stress. Many foods contain substantial amounts of Epi, (e.g. green tea and cocoa). In humans eating such foods may directly or indirectly enhance cognition. We directly test whether operant conditioning training Lymnaea in these natural foods result in the same effects as training snails in pure Epi. We found that exposure to products containing high concentrations of Epi (e.g. green tea and cocoa) during training enhanced memory formation and could even reverse a learning and memory deficit brought about by stress. Epi can be photo-inactivated by exposure to ultraviolet light. We found that following photo-inactivation of Epi, memory enhancement did not occur. Photo-inactivation of foods containing Epi (e,g. green tea) blocked their ability to enhance LTM. Our data are thus consistent with the hypothesis that dietary sources of Epi can have positive benefits on cognitive ability and be able to reverse memory aversive states.

This study investigated the effects of (−)-epicatechin (Epi) in young male borderline hypertensive rats (BHR) during two weeks of treatment (Epi group, 100 mg/kg/day p.o.) and two weeks post treatment (PE group). Epi reduced blood pressure (BP), which persisted for two weeks post treatment. This was associated with delayed reduction of anxiety-like behaviour. Epi significantly increased nitric oxide synthase (NOS) activities in the aorta and left heart ventricle (LHV) vs. the age-matched controls without affecting the brainstem and frontal neocortex. Furthermore, Epi significantly reduced the superoxide production in the aorta and relative content of iron-containing compounds in blood. Two weeks post treatment, the NOS activities and superoxide productions in the heart and aorta did not differ from the age-matched controls. The gene expressions of the NOSs (nNOS, iNOS, eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor-γ (PPAR-γ) remained unaltered in the aorta and LHV of the Epi and PE groups. In conclusion, while Epi-induced a decrease of the rats’ BP persisted for two weeks post treatment, continuous Epi treatments seem to be necessary for maintaining elevated NO production as well as redox balance in the heart and aorta without changes in the NOSs, Nrf2, and PPAR-γ gene expressions.

Cocoa polyphenols play an important role in protection against diseases in which oxidative stress is implicated as a causal or contributing factor. The main aim of this study was to elucidate the influence of different cocoa extracts and main cocoa bioactive compound (–)-epicatechin on cell growth and support of antioxidant cellular barrier in colon adenocarcinoma cell line model (HT29). Results show that the tested cocoa bioactivity results from concerted interactions between epicatechin and other components. Hence, cocoa is a very good example which supports the food synergy concept that is attracting growing interest.

Anthocyanidin reductase (ANR) is a key enzyme in the ANR biosynthetic pathway of flavan-3-ols and proanthocyanidins (PAs) in plants. Herein, we report characterization of the ANR pathway of flavan-3-ols in Shuchazao tea (Camellia sinesis), which is an elite and widely grown cultivar in China and is rich in flavan-3-ols providing with high nutritional value to human health. In our study, metabolic profiling was preformed to identify two conjugates and four aglycones of flavan-3-ols: (-)-epigallocatechin-gallate [(-)-EGCG], (-)-epicatechin-gallate [(-)-ECG], (-)-epigallocatechin [(-)-EGC], (-)-epicatechin [(-)-EC], (+)-catechin [(+)-Ca], and (+)-gallocatechin [(+)-GC], of which (-)-EGCG, (-)-ECG, (-)-EGC, and (-)-EC accounted for 70-85% of total flavan-3-ols in different tissues. Crude ANR enzyme was extracted from young leaves. Enzymatic assays showed that crude ANR extracts catalyzed cyanidin and delphinidin to (-)-EC and (-)-Ca and (-)-EGC and (-)-GC, respectively, in which (-)-EC and (-)-EGC were major products. Moreover, two ANR cDNAs were cloned from leaves, namely CssANRa and CssANRb. His-Tag fused recombinant CssANRa and CssANRb converted cyanidin and delphinidin to (-)-EC and (-)-Ca and (-)-EGC and (-)-GC, respectively. In addition, (+)-EC was observed from the catalysis of recombinant CssANRa and CssANRb. Further overexpression of the two genes in tobacco led to the formation of PAs in flowers and the reduction of anthocyanins. Taken together, these data indicate that the majority of leaf flavan-3-ols in Shuchazao's leaves were produced from the ANR pathway. [ABSTRACT FROM AUTHOR]

Purpose: To characterize and identify metabolites of (-)-epicatechin in microsomal fraction of rat hepatocytes (MFRHs). Methods: A single incubation of (-)-epicatechin (1 mL, 50 ìg/mL) in MFRH (0.5 mg/mL) was used for the generation of metabolites. Thereafter, the sample was subjected to protein precipitation prior to analysis with ultra-high performance liquid chromatography coupled to linear ion-trap orbitrap mass spectrometry (UHPLC-LTQ-Orbitap MS). Results: Nine metabolites of (-)-epicatechin were characterized on the basis of high resolution mass measurement, MS spectra and literature data. Based on their structures, the major metabolic routes of (-)-epicatechin in MFRHs were identified as hydroxylation, dihydroxylation and glycosylation. Conclusion: This is the first report on metabolites of (-)-epicatechin in MFRHs, and it is helpful in gaining deeper insight into the metabolism of (-)-epicatechin in vivo. The results will also provide guidance in research on the pharmacokinetics of new drugs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chiranthodendron pentadactylon Larreat. (Sterculiaceae) is a Mexican plant used in traditional medicine for the treatment of heart disease symptoms and infectious diarrhea. Objective: To evaluate in vitro antiprotozoal and antibacterial activities and in vivo antidiarrheal activity from the flowers of C. pentadactylon using the extract, fractions, and major isolated flavonoids. Materials and methods: Bioassay-guided fractionation of the methanol extract of C. pentadactylon (MECP) led to the isolation of five flavonoids, tiliroside, astragalin, isoquercitrin, (+)-catechin, and (-)-epicatechin. Antimicrobial activities were tested on two protozoa (Entamoeba histolytica and Giardia lamblia) and nine bacterial enteropathogens (two Escherichia coli strains, two Shigella sonnei strains, two Shigella flexneri strains, two Salmonella sp. strains, and Vibrio cholerae) isolated from feces of children with acute diarrhea or dysentery and resistant to chloramphenicol. Also, antidiarrheal activity was tested on cholera toxin-induced diarrhea in male Balb-c mice. Results: Epicatechin was the most potent antiamoebic and antigiardial compound with IC50 values of 1.9 μg/mL for E. histolytica and 1.6 μg/mL for G. lamblia; tiliroside showed moderate antiprotozoal activity against both protozoan. In contrast, in the antibacterial activity, tiliroside was the most potent compound on all microorganisms with minimum inhibitory concentration values less than 0.7 mg/mL. In the case of cholera toxininduced diarrhea, epicatechin was the most potent flavonoid with IC50 of 14.7 mg/kg. Conclusion: Epicatechin and tiliroside were the flavonoids responsible for antimicrobial andantidiarrheal activities of C. pentadactylon. Its antiprotozoal, antibacterial, and antidiarrheal properties are in good agreement with the traditional medicinal use of C. pentadactylon for the treatment of infectious diarrhea. [ABSTRACT FROM AUTHOR]

[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: Hepatitis is a health problem affecting millions of people worldwide and it is the major risk factor for liver cirrhosis. In India, many plants are used to treat hepatitis. But little is known about the effects of (-)-epicatechin a bioactive compound of Phyllanthus niruri (PN) in hepatitis rats. Objective: The present study was designed to explore the antioxidant property of (-)-epicatechin isolated from PN in D-Galactosamine (D-GalN) induced hepatitis rats. Materials and Methods: The rats are divided into five groups as per the experimental design. (-)-Epicatchin pretreatment was given to the hepatitis rats for 21 days and biochemical analysis was carried out. The hepatic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA) and serum markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin, and bilirubin are estimated. Results: All the antioxidant enzymes activities and albumin levels are depleted in hepatitic rats. Whereas GST, ALP, AST, ALT activities and MDA, and bilirubin levels are elevated in hepatitis rats, (-)-epicatechin pretreatment increased all the antioxidant enzymes and decreased the GST, ALP, AST, ALT, and MDA levels in hepatitis rats. However, histopatholoigic studies also proves that (-)-epicatechin pretreatment decreased the tissue damage in hepatitis condition. This is the first report on the antioxidant enzymes and hepatoprotective effect of (-)-epicatechin in hepatitis rats. Conclusion: From this study, we conclude that (-)-epicatechin treatment decreased the oxidative damage in hepatitis rats. [ABSTRACT FROM AUTHOR]

The modulation of longevity genes and aging-associated signaling pathways using pharmacological agents is one of the potential ways to prolong the lifespan and increase the vitality of an organism. Phytochemicals flavonoids and non-steroidal anti-inflammatory drugs have a large potential as geroprotectors. The goal of the present study was to investigate the effects of long-term and short-term consumption of quercetin, (-)-epicatechin, and ibuprofen on the lifespan, resistance to stress factors (paraquat, hyperthermia, g-radiation, and starvation), as well as age-dependent physiological parameters (locomotor activity and fecundity) of Drosophila melanogaster. The long-term treatment with quercetin and (-)-epicatechin didn't change or decreased the lifespan of males and females. In contrast, the short-term treatment with flavonoids had a beneficial effect and stimulated the resistance to paraquat and acute g-irradiation. The short-term ibuprofen consumption had a positive effect on the lifespan of females when it was carried out at the middle age (30-40 days), and to the survival of flies under conditions of oxidative and genotoxic stresses. However, it didn't change the lifespan of males and females after the treatment during first 10 days of an imago life. Additionally, quercetin, (-)-epicatechin, and ibuprofen decreased the spontaneous locomotor activity of males, but had no effect of stimulated the physical activity and fecundity of females. Revealed quercetin, (-)-epicatechin, and ibuprofen activity can be associated with the stimulation of stress response mechanisms through the activation of pro-longevity pathways, or the induction of hormesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

(-)-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. [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]

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 3 h after TBI and then every 24 h 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. [ABSTRACT FROM AUTHOR]

There is evidence implicating oxidative stress (OS) as the cause of the deleterious effects of aging. In this study, we evaluated the capacity of the flavanol (-)-epicatechin (Epi) to reduce aging-induced OS and restore mitochondrial biogenesis, as well as, structural and functional endpoints in aged mice. Senile (S; 26-month-old) C57BL/6 male mice were randomly assigned to receive either water (vehicle) or 1mg/kg of Epi via oral gavage (twice daily) for 15 days. Young (Y; 6-month-old) mice were used as controls. In S brain, kidney, heart, and skeletal muscle (compared with Y animals) an increase in OS was observed as evidenced by increased protein-free carbonyls and decreased reduced glutathione levels as well as sirtuin 3, superoxide dismutase 2, catalase, thioredoxin and glutathione peroxidase protein levels. Well-recognized factors (eg, sirtuin 1) that regulate mitochondrial biogenesis and mitochondrial structure- and/or function-related endpoints (eg, mitofilin and citrate synthase) protein levels were also reduced in S organs. In contrast, the aging biomarker senescence-associated β-galactosidase was increased in S compared with Y animals, and Epi administration reduced levels towards those observed in Y animals. Altogether, these data suggest that Epi is capable of shifting the biology of S mice towards that of Y animals. [ABSTRACT FROM AUTHOR]

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 + (K V ) channels, and glibenclamide, a selective ATP-sensitive K + (K ATP ) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca 2+ -activated K + channels (BK Ca ), almost completely inhibited the relaxation. In rings pre-contracted by 80 mM 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 K V channels, as well as BK Ca and K ATP 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. [ABSTRACT FROM AUTHOR]