(-)-Epicatechin is an orally active flavan-3-ol polyphenol and a COX-1 inhibitor (IC50=3.2μM). (-)-Epicatechin can activate the PI3K/Akt pathway to phosphorylate endothelial nitric oxide synthase and inhibit NADPH oxidase, thereby increasing nitric oxide bioavailability and improving vascular endothelial function. (-)-Epicatechin can activate Nrf2 antioxidant signaling and promote mitochondrial biogenesis. (-)-Epicatechin can be used in research related to cardiovascular diseases, metabolic diseases, muscle-related diseases, cancer, inflammation, diabetes, and neurodegenerative diseases[1-4].
In vitro, pretreatment of Caco-2 cells with 0.5-5μM (-)-Epicatechin for 6 hours followed by treatment with 20ng/mL tumor necrosis factor alpha (TNF-α) inhibited TNF-α-triggered NADPH oxidase-mediated increase in oxidant generation, NF-κB and ERK1/2 activation, and prevented the decrease in transepithelial electrical resistance and cell monolayer permeabilization[5]. Treatment of PMA and IL-1α-activated EL4.BU.OU6 cells with 200-400μM (-)-Epicatechin for 24 hours dose-dependently reduced IL-2Rα expression, inhibited IL-2 secretion, and did not change cell viability[6]. Treatment of HepG2 cells with 1-100μM (-)-Epicatechin for 18 hours reduced cell viability, promoted cell proliferation, and decreased reactive oxygen species generation[7].
In vivo, feeding C57BL/6J mice a diet supplemented with 20mg/kg (-)-Epicatechin for 15 weeks improved glucose tolerance and insulin tolerance, reduced fasted and fed plasma glucose and insulin levels, decreased plasma triglyceride and free fatty acid concentrations, and attenuated body weight gain[8]. Feeding C57BL/6J mice a diet supplemented with 20mg/kg (-)-Epicatechin for 15 weeks increased plasma glucagon-like peptide 1 concentration, upregulated ileal proglucagon mRNA levels, and decreased plasma dipeptidyl peptidase IV activity[9]. Feeding high fat diet-fed C57BL/6J mice a diet supplemented with 20mg/kg (-)-Epicatechin for 15 weeks prevented thoracic periaortic adipose tissue expansion, attenuated high fat diet-induced fat whitening, and suppressed the increase in plasma glucose and total cholesterol[10].
References:
[1] Daussin FN, Heyman E, Burelle Y. Effects of (-)-epicatechin on mitochondria. Nutr Rev. 2021 Jan 1;79(1):25-41.
[2] Bernatova I. Biological activities of (-)-epicatechin and (-)-epicatechin-containing foods: Focus on cardiovascular and neuropsychological health. Biotechnol Adv. 2018 May-Jun;36(3):666-681.
[3] Lee I. Regulation of Cytochrome c Oxidase by Natural Compounds Resveratrol, (-)-Epicatechin, and Betaine. Cells. 2021 May 29;10(6):1346.
[4] Ávila-Avilés RD, Bahena-Culhuac E, Hernández-Hernández JM. (-)-Epicatechin metabolites as a GPER ligands: a theoretical perspective. Mol Divers. 2025 Jun;29(3):2099-2115.
[5] Contreras TC, Ricciardi E, Cremonini E, et al. (-)-Epicatechin in the prevention of tumor necrosis alpha-induced loss of Caco-2 cell barrier integrity. Arch Biochem Biophys. 2015 May 15;573:84-91.
[6] Ramiro E, Franch A, Castellote C, et al. Effect of Theobroma cacao flavonoids on immune activation of a lymphoid cell line. Br J Nutr. 2005 Jun;93(6):859-66.
[7] Granado-Serrano AB, Marín MA, Izquierdo-Pulido M, et al. Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. J Agric Food Chem. 2007 Feb;55(5):2020-7.
[8] Cremonini E, Bettaieb A, Haj FG, et al. (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice. Arch Biochem Biophys. 2016 Jun;599:13-21.
[9] Cremonini E, Daveri E, Mastaloudis A, et al. (-)-Epicatechin and anthocyanins modulate GLP-1 metabolism: evidence from C57BL/6J mice and GLUTag cells. J Nutr. 2021 Jun;151(6):1497-506.
[10] Hid EJ, Fischerman L, Piotrkowski B, et al. (-)-Epicatechin protects thoracic aortic perivascular adipose tissue from whitening in high-fat fed mice. Food Funct. 2020 Jul;11(7):5709-22.