( -)-Epicatechin and Cardiometabolic Risk Factors: a Focus on Potential Mechanisms of Action

Overview

Journal Pflugers Arch

Specialty Physiology

Date 2021 Nov 23

PMID 34812946

Citations 7

Authors

Ezequiel J Hid

Juana I Mosele

Paula D Prince

Cesar G Fraga

Monica Galleano

Affiliations

Soon will be listed here.

Abstract

This review summarizes experimental evidence on the beneficial effects of ( -)-epicatechin (EC) attenuating major cardiometabolic risk factors, i.e., dyslipidemias, obesity (adipose tissue dysfunction), hyperglycemia (insulin resistance), and hypertension (endothelial dysfunction). Studies in humans are revised and complemented with experiments in animal models, and cultured cells, aiming to understand the molecular mechanisms involved in EC-mediated effects. Firstly, an assessment of EC metabolism gives relevance to both conjugated-EC metabolites product of host metabolism and microbiota-derived species. Integration and analysis of results stress the maintenance of redox homeostasis and mitigation of inflammation as relevant processes associated with cardiometabolic diseases. In these processes, EC appears having significant effects regulating NADPH oxidase (NOX)-dependent oxidant production, nitric oxide (NO) production, and energy homeostasis (mitochondrial biogenesis and function). The potential participation of cell membranes and membrane-bound receptors is also discussed in terms of direct molecular action of EC and EC metabolites reaching cells and tissues.

Citing Articles

Green Tea Polyphenol (-)-Epicatechin Pretreatment Mitigates Hepatic Steatosis in an In Vitro MASLD Model.

Hefer M, Petrovic A, Roguljic L, Kolaric T, Kizivat T, Wu C Curr Issues Mol Biol. 2024; 46(8):8981-8994.

PMID: 39194748 PMC: 11352320. DOI: 10.3390/cimb46080531.

Identification of PANoptosis-related signature reveals immune infiltration characteristics and immunotherapy responses for renal cell carcinoma.

Xu Y, Hua J, Que H, Zeng T, Li Q, Deng J BMC Cancer. 2024; 24(1):292.

PMID: 38439022 PMC: 10913266. DOI: 10.1186/s12885-024-12067-2.

Coffee Silverskin Phytocompounds as a Novel Anti-Aging Functional Food: A Pharmacoinformatic Approach Combined with In Vitro Study.

Hayes C, Nurkolis F, Laksemi D, Chung S, Park M, Choi M Molecules. 2023; 28(20).

PMID: 37894516 PMC: 10609341. DOI: 10.3390/molecules28207037.

Targeted UHPLC-MS Analysis Reveals Disparate Polyphenol Composition and Concentration in Muscadine Grape Supplements with Proportional Antioxidant Activity.

Chappell M, Duncan A, Melo A, Schaich C, Pirro N, Diz D Antioxidants (Basel). 2022; 11(11).

PMID: 36358490 PMC: 9686579. DOI: 10.3390/antiox11112117.

Targeting Oxidative Stress in Intracerebral Hemorrhage: Prospects of the Natural Products Approach.

Zheng Y, Li R, Fan X Antioxidants (Basel). 2022; 11(9).

PMID: 36139885 PMC: 9495708. DOI: 10.3390/antiox11091811.

References

Andersson C, Lyass A, Vasan R, Massaro J, DAgostino Sr R, Robins S . Long-term risk of cardiovascular events across a spectrum of adverse major plasma lipid combinations in the Framingham Heart Study. Am Heart J. 2014; 168(6):878-83.e1. DOI: 10.1016/j.ahj.2014.08.007. View

Arnett D, Blumenthal R, Albert M, Buroker A, Goldberger Z, Hahn E . 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019; 74(10):e177-e232. PMC: 7685565. DOI: 10.1016/j.jacc.2019.03.010. View

Barnett C, Moreno-Ulloa A, Shiva S, Ramirez-Sanchez I, Taub P, Su Y . Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (-)-epicatechin in healthy volunteers. Food Funct. 2015; 6(3):824-33. PMC: 4357542. DOI: 10.1039/c4fo00596a. View

Beretz A, Anton R, STOCLET J . Flavonoid compounds are potent inhibitors of cyclic AMP phosphodiesterase. Experientia. 1978; 34(8):1054-5. DOI: 10.1007/BF01915343. View

Bernatova I, Liskova S . Mechanisms Modified by (-)-Epicatechin and Taxifolin Relevant for the Treatment of Hypertension and Viral Infection: Knowledge from Preclinical Studies. Antioxidants (Basel). 2021; 10(3). PMC: 8002320. DOI: 10.3390/antiox10030467. View

Bettaieb A, Vazquez Prieto M, Rodriguez Lanzi C, Miatello R, Haj F, Fraga C . (-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress. Free Radic Biol Med. 2014; 72:247-56. PMC: 4077617. DOI: 10.1016/j.freeradbiomed.2014.04.011. View

Bettaieb A, Cremonini E, Kang H, Kang J, Haj F, Oteiza P . Anti-inflammatory actions of (-)-epicatechin in the adipose tissue of obese mice. Int J Biochem Cell Biol. 2016; 81(Pt B):383-392. PMC: 5514545. DOI: 10.1016/j.biocel.2016.08.044. View

Bondonno N, Lewis J, Blekkenhorst L, Bondonno C, Shin J, Croft K . Association of flavonoids and flavonoid-rich foods with all-cause mortality: The Blue Mountains Eye Study. Clin Nutr. 2019; 39(1):141-150. DOI: 10.1016/j.clnu.2019.01.004. View

Borges G, van der Hooft J, Crozier A . A comprehensive evaluation of the [2-C](-)-epicatechin metabolome in rats. Free Radic Biol Med. 2016; 99:128-138. DOI: 10.1016/j.freeradbiomed.2016.08.001. View

10.

Borges G, Ottaviani J, van der Hooft J, Schroeter H, Crozier A . Absorption, metabolism, distribution and excretion of (-)-epicatechin: A review of recent findings. Mol Aspects Med. 2017; 61:18-30. DOI: 10.1016/j.mam.2017.11.002. View

11.

Brossette T, Hundsdorfer C, Kroncke K, Sies H, Stahl W . Direct evidence that (-)-epicatechin increases nitric oxide levels in human endothelial cells. Eur J Nutr. 2011; 50(7):595-9. DOI: 10.1007/s00394-011-0172-9. View

12.

Cheung S, Huang Y, Kwan H, Chung H, Yao X . Activation of transient receptor potential vanilloid 3 channel suppresses adipogenesis. Endocrinology. 2015; 156(6):2074-86. DOI: 10.1210/en.2014-1831. View

13.

Cordero-Herrera I, Martin M, Bravo L, Goya L, Ramos S . Cocoa flavonoids improve insulin signalling and modulate glucose production via AKT and AMPK in HepG2 cells. Mol Nutr Food Res. 2013; 57(6):974-85. DOI: 10.1002/mnfr.201200500. View

14.

Cremonini E, Bettaieb A, Haj F, Fraga C, Oteiza P . (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice. Arch Biochem Biophys. 2016; 599:13-21. PMC: 5523407. DOI: 10.1016/j.abb.2016.03.006. View

15.

Cremonini E, Wang Z, Bettaieb A, Adamo A, Daveri E, Mills D . (-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance. Redox Biol. 2017; 14:588-599. PMC: 5691220. DOI: 10.1016/j.redox.2017.11.002. View

16.

Cremonini E, Fraga C, Oteiza P . (-)-Epicatechin in the control of glucose homeostasis: Involvement of redox-regulated mechanisms. Free Radic Biol Med. 2018; 130:478-488. DOI: 10.1016/j.freeradbiomed.2018.11.010. View

17.

Cremonini E, Iglesias D, Kang J, Lombardo G, Mostofinejad Z, Wang Z . (-)-Epicatechin and the comorbidities of obesity. Arch Biochem Biophys. 2020; 690:108505. DOI: 10.1016/j.abb.2020.108505. View

18.

Cremonini E, Daveri E, Mastaloudis A, Oteiza P . (-)-Epicatechin and Anthocyanins Modulate GLP-1 Metabolism: Evidence from C57BL/6J Mice and GLUTag Cells. J Nutr. 2021; 151(6):1497-1506. PMC: 8659349. DOI: 10.1093/jn/nxab029. View

19.

Cristancho A, Lazar M . Forming functional fat: a growing understanding of adipocyte differentiation. Nat Rev Mol Cell Biol. 2011; 12(11):722-34. PMC: 7171550. DOI: 10.1038/nrm3198. View

20.

Daussin F, Heyman E, Burelle Y . Effects of (-)-epicatechin on mitochondria. Nutr Rev. 2020; 79(1):25-41. DOI: 10.1093/nutrit/nuaa094. View