Epicatechin

1 Aesculus sp. 2 Agrimonia sp. 3 Begonia sp. 4 Calluna sp. 5 Camellia sp. 6 Casuarina sp. 7 Ceratonia sp. 8 Cinnamomum sp. 9 Cola sp. 10 Crataegus sp. 11 Ephedra sp. 12 Geranium sp. 13 Ginkgo sp. 14 Harungana sp. 15 Hippophae sp. 16 Humulus sp. 17 Illicium sp. 18 Juniperus sp. 19 Larix sp. 20 Malus sp. 21 Paullinia sp. 22 Persicaria sp. 23 Phyllanthus sp. 24 Polygonum sp. 25 Primula sp. 26 Pterocarpus sp. 27 Quercus sp. 28 Rheum sp. 29 Salix sp. 30 Theobroma sp. 31 Uncaria sp. 32 Vaccinium sp. 33 Vitis sp.

(-)-epicatechin is a flavonoid that increases NO levels and an inducer of pancreatic β-cell regeneration [1] [2].

β cells are a subset of cells in the pancreatic islets and play an important role in regulating glucose homeostasis through the production of insulin.

(-)-epicatechin is an inducer of pancreatic β-cell regeneration. In murine macrophages, (-)-epicatechin induced nitrite accumulation induced by interferon-γ/lipopolysaccharide with IC50 value of 0.5 mM. Also, (-)-epicatechin inhibited nitration of free tyrosine induced by 0.1 and 1 mM peroxynitrite with IC50 values of 6.6 and 28.0 µM, respectively. In HL-60 cells, (-)-epicatechin inhibited nitration of protein-bound tyrosine induced by phorbol 12-myristate 13-acetate with IC50 value of 10-100 µM [2]. In human endothelial cells (HUVEC), (-)-epicatechin (0.3-10 µM) increased NO levels, suggesting its vasodilatory properties [3].

In alloxan diabetic rats, (-)-epicatechin (30 mg/kg) lowered blood sugar and restored the amount of beta-cells against alloxan-induced necrosis of the beta-cell population in the pancreatic islets. In rats, (-)-epicatechin was non-toxic up to 1 g/kg [1]. In rats, oral administration of (-)-epicatechin metabolized to 3’-O-methyl-(-)-epicatechin and 4’-O-methyl-(-)-epicatechin [4].

References:
[1].  Chakravarthy BK, Gupta S, Gambhir SS, et al. Pancreatic beta-cell regeneration in rats by (-)-epicatechin. Lancet, 1981, 2(8249): 759-760.
[2].  Wippel R, Rehn M, Gorren AC, et al. Interference of the polyphenol epicatechin with the biological chemistry of nitric oxide- and peroxynitrite-mediated reactions. Biochem Pharmacol, 2004, 67(7): 1285-1295.
[3].  Brossette T, Hundsdörfer C, Kröncke KD, et al. Direct evidence that (-)-epicatechin increases nitric oxide levels in human endothelial cells. Eur J Nutr, 2011, 50(7): 595-599.
[4].  Okushio K, Suzuki M, Matsumoto N, et al. Identification of (-)-epicatechin metabolites and their metabolic fate in the rat. Drug Metab Dispos, 1999, 27(2): 309-316.

Analysis of the mechanisms underlying the antinociceptive effect of epicatechin in diabetic rats.[Pubmed:24012613]

Life Sci. 2013 Oct 17;93(17):637-45.

AIMS: The purpose of this study was to investigate the antinociceptive effect of Epicatechin as well as the possible mechanisms of action in diabetic rats. MAIN METHODS: Rats were injected with streptozotocin to produce hyperglycemia. The formalin test was used to assess the nociceptive activity. KEY FINDINGS: Acute pre-treatment with Epicatechin (0.03-30 mg/kg, i.p.) prevented formalin-induced nociception in diabetic rats. Furthermore, daily or every other day treatment for 2 weeks with Epicatechin (0.03-30 mg/kg, i.p.) also prevented formalin-induced nociception in diabetic rats. Acute Epicatechin-induced antinociception was prevented by l-NAME (N(omega)-nitro-l-arginine methyl ester hydrochloride, 1-10mg/kg, non-selective nitric oxide synthesis inhibitor), 7-nitroindazole (0.1-1mg/kg, selective neuronal nitric oxide synthesis inhibitor), ODQ (1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one, 0.2-2mg/kg, guanylyl cyclase inhibitor) or glibenclamide (1-10mg/kg, ATP-sensitive K(+) channel blocker). Moreover, Epicatechin (3mg/kg)-induced antinociception was fully prevented by methiothepin (0.1-1mg/kg, serotonergic receptor antagonist), WAY-100635 (0.03-0.3mg/kg, selective 5-HT1A receptor antagonist) or SB-224289 (0.03-0.3mg/kg, selective 5-HT1B receptor antagonist). In contrast, BRL-15572 (0.03-0.3mg/kg, selective 5-HT1D receptor antagonist) only slightly prevented the antinociceptive effect of Epicatechin. Naloxone (0.1-1mg/kg, opioid antagonist) did not modify Epicatechin's effect. SIGNIFICANCE: Data suggest the involvement of the nitric oxide-cyclic GMP-K(+) channel pathway as well as activation of 5-HT1A and 5HT1B, and at a lesser extent, 5-HT1D, but not opioid, receptors in the antinociceptive effect of Epicatechin in diabetic rats. Our data suggest that acute or chronic treatment with Epicatechin may prove to be effective to treat nociceptive hypersensitivity in diabetic patients.

Plant-derived flavanol (-)epicatechin enhances angiogenesis and retention of spatial memory in mice.[Pubmed:17537957]

J Neurosci. 2007 May 30;27(22):5869-78.

Diet and exercise have a profound impact on brain function. In particular, natural nutrients found in plants may influence neuronal survival and plasticity. Here, we tested whether consumption of a plant-derived flavanol, (-)Epicatechin, enhances cognition in sedentary or wheel-running female C57BL/6 mice. Retention of spatial memory in the water maze was enhanced by ingestion of (-)Epicatechin, especially in combination with exercise. Improved spatial memory was associated with increased angiogenesis and neuronal spine density, but not newborn cell survival, in the dentate gyrus of the hippocampus. Moreover, microarray analysis showed upregulation of genes associated with learning and downregulation of markers of neurodegeneration in the hippocampus. Together, our data show that ingestion of a single flavanol improves spatial memory retention in adult mammals.

(-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans.[Pubmed:16418281]

Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1024-9.

Epidemiological and medical anthropological investigations suggest that flavanol-rich foods exert cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by a decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol-rich cocoa was associated with acute elevations in levels of circulating NO species, an enhanced FMD response of conduit arteries, and an augmented microcirculation. In addition, the concentrations and the chemical profiles of circulating flavanol metabolites were determined, and multivariate regression analyses identified (-)-Epicatechin and its metabolite, Epicatechin-7-O-glucuronide, as independent predictors of the vascular effects after flavanol-rich cocoa ingestion. A mixture of flavanols/metabolites, resembling the profile and concentration of circulating flavanol compounds in plasma after cocoa ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol-induced relaxation, as well as the in vivo increases in FMD, were abolished by inhibition of NO synthase. Oral administration of chemically pure (-)-Epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the concept that a chronic intake of high-flavanol diets is associated with prolonged, augmented NO synthesis is supported by data that indicate a correlation between the chronic consumption of a cocoa flavanol-rich diet and the augmented urinary excretion of NO metabolites. Collectively, our data demonstrate that the human ingestion of the flavanol (-)-Epicatechin is, at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa.

Epicatechin and catechin modulate endothelial activation induced by platelets of patients with peripheral artery disease.[Pubmed:25180068]

Oxid Med Cell Longev. 2014;2014:691015.

Platelet activation contributes to the alteration of endothelial function, a critical initial step in atherogenesis through the production and release of prooxidant mediators. There is uncertainty about the precise role of polyphenols in interaction between platelets and endothelial cells (ECs). We aimed to investigate whether polyphenols are able to reduce endothelial activation induced by activated platelets. First, we compared platelet activation and flow-mediated dilation (FMD) in 10 healthy subjects (HS) and 10 patients with peripheral artery disease (PAD). Then, we evaluated the effect of Epicatechin plus catechin on platelet-HUVEC interaction by measuring soluble cell adhesion molecules (CAMs), NOx production, and eNOS phosphorylation (p-eNOS) in HUVEC. Compared to HS, PAD patients had enhanced platelet activation. Conversely, PAD patients had lower FMD than HS. Supernatant of activated platelets from PAD patients induced an increase of sCAMs release and a decrease of p-eNOS and nitric oxide (NO) bioavailability compared to unstimulated HUVEC. Coincubation of HUVEC, with supernatant of PAD platelets patients, pretreated with a scalar dose of the polyphenols, resulted in a decrease of sCAMs release and in an increase of p-eNOS and NO bioavailability. This study demonstrates that Epicatechin plus catechin reduces endothelial activation induced by activated platelets.

Antioxidant activity and diffusion of catechin and epicatechin from antioxidant active films made of poly(L-lactic acid).[Pubmed:22681400]

J Agric Food Chem. 2012 Jul 4;60(26):6515-23.

Active membranes and food packaging containing antioxidants like catechin and Epicatechin, combined with the use of materials made of biopolymers obtained from renewable sources, could create a novel alternative to reduce oxidation in food, pharmaceutical, and cosmetic products. Poly(94% L-lactic acid) films containing 1.28% catechin and 1.50% Epicatechin were extruded in a pilot plant-scale extrusion machine. The diffusion kinetics of catechin and Epicatechin into 95% ethanol at 20, 30, 40, and 50 degrees C and 50% ethanol at 40 degrees C displayed Fickian release behavior and diffusion coefficients between 0.5 and 50 x 10(-11) cm(2)/s. According to the Arrhenius equation, the energy of activation for the diffusion of catechin and Epicatechin in the films was 110.43 and 98.92 kJ/mol, respectively. The antioxidant activity of the films was measured in methanol extracts containing 46.42 mug/mL of catechin and 57.52 mug/mL of Epicatechin as 32.90 and 36.68% of scavenging the 2,2-diphenyl-1-picrylhydrazyl radical, respectively.

Effect of catechin/epicatechin dietary intake on endothelial dysfunction biomarkers and proinflammatory cytokines in aorta of hyperhomocysteinemic mice.[Pubmed:22899103]

Eur J Nutr. 2013 Apr;52(3):1243-50.

PURPOSE: Hyperhomocysteinemia is well recognized as an independent risk factor for the development of premature atherosclerosis. Atherosclerosis, however, may be prevented by polyphenols, potent antioxidant compounds with anti-atherogenic properties. Previously, we used cystathionine beta synthase-deficient mice [Cbs (+/-)] fed a high-methionine diet-a murine model of hyperhomocysteinemia-to show that daily intake of a red wine polyphenolic extract, mainly comprised of catechin and Epicatechin, has a beneficial effect on aortic expression of endothelial dysfunction biomarkers and pro-inflammatory cytokines. The aim of the present study was to understand whether catechin and Epicatechin, in purified forms, have anti-atherogenic effects in hyperhomocysteinemia. METHODS: Cbs (+/-) mice received 50 mug of catechin and/or Epicatechin daily in drinking water for 1 month. Plasma homocysteine (Hcy) level and aortic expression of several endothelial dysfunction biomarkers (Vcam-1, Icam-1, E-selectin, and Lox-1) and pro-inflammatory cytokines (Tnf-alpha, Il-6) were assessed. RESULTS: We found that both catechin and Epicatechin had a beneficial effect on plasma homocysteine levels and endothelial dysfunction biomarker expression; however, only catechin had a beneficial effect on pro-inflammatory cytokine expression. Further, when both polyphenols were given, a beneficial effect was observed only on pro-inflammatory cytokine expression. CONCLUSIONS: Catechin seems to be a more potent anti-atherogenic compound than Epicatechin in hyperhomocysteinemia and should be considered as a novel therapeutic approach against endothelial dysfunction induced by this condition.

(-)Epicatechin stimulates ERK-dependent cyclic AMP response element activity and up-regulates GluR2 in cortical neurons.[Pubmed:17298385]

J Neurochem. 2007 Jun;101(6):1596-606.

Emerging evidence suggests that the cellular actions of flavonoids relate not simply to their antioxidant potential but also to the modulation of protein kinase signalling pathways. We investigated in primary cortical neurons, the ability of the flavan-3-ol, (-)Epicatechin, and its human metabolites at physiologically relevant concentrations, to stimulate phosphorylation of the transcription factor cAMP-response element binding protein (CREB), a regulator of neuronal viability and synaptic plasticity. (-)Epicatechin at 100-300 nmol/L stimulated a rapid, extracellular signal-regulated kinase (ERK)- and PI3K-dependent, increase in CREB phosphorylation. At micromolar concentrations, stimulation was no longer apparent and at the highest concentration tested (30 mumol/L) (-)Epicatechin was inhibitory. (-)Epicatechin also stimulated ERK and Akt phosphorylation with similar bell-shaped concentration-response characteristics. The human metabolite 3'-O-methyl-(-)Epicatechin was as effective as (-)Epicatechin at stimulating ERK phosphorylation, but (-)Epicatechin glucuronide was inactive. (-)Epicatechin and 3'-O-methyl-(-)Epicatechin treatments (100 nmol/L) increased CRE-luciferase activity in cortical neurons in a partially ERK-dependent manner, suggesting the potential to increase CREB-mediated gene expression. mRNA levels of the glutamate receptor subunit GluR2 increased by 60%, measured 18 h after a 15 min exposure to (-)Epicatechin and this translated into an increase in GluR2 protein. Thus, (-)Epicatechin has the potential to increase CREB-regulated gene expression and increase GluR2 levels and thus modulate neurotransmission, plasticity and synaptogenesis.

Protective effect of epicatechin, epicatechin gallate, and quercetin on lipid peroxidation in phospholipid bilayers.[Pubmed:8311465]

Arch Biochem Biophys. 1994 Jan;308(1):278-84.

Antioxidative effect of (-)-Epicatechin,(-)-Epicatechin gallate, and quercetin was examined by measuring the inhibition of lipid peroxidation in large unilamellar liposomes composed of egg yolk phosphatidylcholine (PC). These catechol-type flavonoids were stable in the liposomal suspension. They retarded the accumulation of PC-hydroperoxides depending on their concentrations when the suspension was exposed to an water-soluble radical initiator, 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH). Their inhibitory effects lasted longer than that of alpha-tocopherol. When each flavonoid and alpha-tocopherol were mixed in the liposomes, Epicatechin and Epicatechin gallate disappeared in favor of alpha-tocopherol. Quercetin also decreased faster than alpha-tocopherol in the initial stage of incubation. Kinetic studies of the inhibition of radical chain oxidation of methyl linoleate in solution demonstrated that the rate constants for the inhibition of oxidation by these flavonoids (kinh) were 5-20 times smaller than that by alpha-tocopherol. It is likely that the flavonoids are localized near the surface of phospholipid bilayers suitable for scavenging aqueous oxygen radicals and thereby they prevent the consumption of lipophilic alpha-to-copherol. Epicatechin and epicatecin gallate gave smaller kinh values than quercetin. Voltammograms of these compounds showed that electron-donating ability of catechins was lower than that of quercetin. However, antioxidative effects of catechins were comparable to that of quercetin in AAPH-initiated peroxidation of the liposomal suspension. It is concluded that catechins and quercetin serve as powerful antioxidants against lipid peroxidation when phospholipid bilayers are exposed to aqueous oxygen radicals.

(-)-Epicatechin inhibits cyclooxygenase-1 (COX-1) with an IC50 of 3.2 μM. (-)-Epicatechin inhibits the IL-1β-induced expression of iNOS by blocking the nuclear localization of the p65 subunit of NF-κB.

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