Cardiovascular Effects of Caffeic Acid and Its Derivatives: A Comprehensive Review

Overview

Journal Front Physiol

Date 2020 Dec 21

PMID 33343392

Citations 34

Authors

Henrique Silva

Nuno Miguel F Lopes

Affiliations

Soon will be listed here.

Abstract

Caffeic acid (CA) and its phenethyl ester (CAPE) are naturally occurring hydroxycinnamic acids with an interesting array of biological activities; e.g., antioxidant, anti-inflammatory, antimicrobial and cytostatic. More recently, several synthetic analogs have also shown similar properties, and some with the advantage of added stability. The actions of these compounds on the cardiovascular system have not been thoroughly explored despite presenting an interesting potential. Indeed the mechanisms underlying the vascular effects of these compounds particularly need clarifying. The aim of this paper is to provide a comprehensive and up-to-date review on current knowledge about CA and its derivatives in the cardiovascular system. Caffeic acid, CAPE and the synthetic caffeic acid phenethyl amide (CAPA) exhibit vasorelaxant activity by acting on the endothelial and vascular smooth muscle cells. Vasorelaxant mechanisms include the increased endothelial NO secretion, modulation of calcium and potassium channels, and modulation of adrenergic receptors. Together with a negative chronotropic effect, vasorelaxant activity contributes to lower blood pressure, as several preclinical studies show. Their antioxidant, anti-inflammatory and anti-angiogenic properties contribute to an important anti-atherosclerotic effect, and protect tissues against ischemia/reperfusion injuries and the cellular dysfunction caused by different physico-chemical agents. There is an obvious shortage of studies to further explore these compounds' potential in vascular physiology. Nevertheless, their favorable pharmacokinetic profile and overall lack of toxicity make these compounds suitable for clinical studies.

Citing Articles

The Effects of White Wine and Ethanol Consumption on the Proliferative Phase of Repair After a Surgically Induced Myocardial Infarction in Rats.

Boban D, Grkovic I, Dzelalija A, Gujinovic D, Mudnic I, Boban M Nutrients. 2025; 17(4).

PMID: 40005027 PMC: 11858397. DOI: 10.3390/nu17040699.

The chemical composition analysis of Yixin Tongmai Granules using UHPLC-MS/MS and exploration of its potential mechanism in treatment of coronary artery disease based on network pharmacology and molecular docking.

Li H, Zhu Y Medicine (Baltimore). 2025; 104(8):e41620.

PMID: 39993113 PMC: 11856895. DOI: 10.1097/MD.0000000000041620.

In vitro antioxidant, anticancer and in silico studies of polyphenol enriched leaf extract of Asystasia gangetica.

Dilkalal A, Annapurna A, Umesh T Sci Rep. 2024; 14(1):28374.

PMID: 39551894 PMC: 11570673. DOI: 10.1038/s41598-024-79996-7.

Caffeic acid phenethyl ester attenuates infection in vivo: antioxidants and NF-κB have a protective role against stomach damage.

Al-Ghamdi A J Med Life. 2024; 17(6):574-581.

PMID: 39296435 PMC: 11407487. DOI: 10.25122/jml-2023-0544.

Antioxidant Scavenging of the Superoxide Radical by Yerba Mate ( and Black Tea Plus Caffeic and Chlorogenic Acids, as Shown via DFT and Hydrodynamic Voltammetry.

Caruso F, Sakib R, Belli S, Caruso A, Rossi M Int J Mol Sci. 2024; 25(17).

PMID: 39273291 PMC: 11394812. DOI: 10.3390/ijms25179342.

References

Ozyurt B, Iraz M, Koca K, Ozyurt H, Sahin S . Protective effects of caffeic acid phenethyl ester on skeletal muscle ischemia-reperfusion injury in rats. Mol Cell Biochem. 2006; 292(1-2):197-203. DOI: 10.1007/s11010-006-9232-5. View

Tan J, Ma Z, Han L, Du R, Zhao L, Wei X . Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2005; 289(5):H2265-71. DOI: 10.1152/ajpheart.01106.2004. View

Cotecchia S . The α1-adrenergic receptors: diversity of signaling networks and regulation. J Recept Signal Transduct Res. 2010; 30(6):410-9. PMC: 3018134. DOI: 10.3109/10799893.2010.518152. View

Lee S, Ku H, Kuo Y, Yang K, Tu P, Chiu H . Caffeic acid ethanolamide prevents cardiac dysfunction through sirtuin dependent cardiac bioenergetics preservation. J Biomed Sci. 2015; 22:80. PMC: 4578267. DOI: 10.1186/s12929-015-0188-1. View

Ahn M, Kunimasa K, Kumazawa S, Nakayama T, Kaji K, Uto Y . Correlation between antiangiogenic activity and antioxidant activity of various components from propolis. Mol Nutr Food Res. 2008; 53(5):643-51. DOI: 10.1002/mnfr.200800021. View

Saavedra-Lopes M, Ramalho F, N Z Ramalho L, Andrade-Silva A, Martinelli A, Jordao Jr A . The protective effect of CAPE on hepatic ischemia/reperfusion injury in rats. J Surg Res. 2008; 150(2):271-7. DOI: 10.1016/j.jss.2008.01.039. View

Kudugunti S, Thorsheim H, Yousef M, Guan L, Moridani M . The metabolic bioactivation of caffeic acid phenethyl ester (CAPE) mediated by tyrosinase selectively inhibits glutathione S-transferase. Chem Biol Interact. 2011; 192(3):243-56. PMC: 3706206. DOI: 10.1016/j.cbi.2011.03.015. View

Agunloye O, Oboh G, Ademiluyi A, Ademosun A, Afolabi Akindahunsi A, Oyagbemi A . Cardio-protective and antioxidant properties of caffeic acid and chlorogenic acid: Mechanistic role of angiotensin converting enzyme, cholinesterase and arginase activities in cyclosporine induced hypertensive rats. Biomed Pharmacother. 2018; 109:450-458. DOI: 10.1016/j.biopha.2018.10.044. View

Khanna A, Cowled P, Fitridge R . Nitric oxide and skeletal muscle reperfusion injury: current controversies (research review). J Surg Res. 2005; 128(1):98-107. DOI: 10.1016/j.jss.2005.04.020. View

10.

Wallerath T, Li H, Godtel-Ambrust U, Schwarz P, Forstermann U . A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase. Nitric Oxide. 2005; 12(2):97-104. DOI: 10.1016/j.niox.2004.12.004. View

11.

Paracatu L, Faria C, Quinello C, Renno C, Palmeira P, Zeraik M . Caffeic Acid phenethyl ester: consequences of its hydrophobicity in the oxidative functions and cytokine release by leukocytes. Evid Based Complement Alternat Med. 2014; 2014:793629. PMC: 4164378. DOI: 10.1155/2014/793629. View

12.

Konishi Y, Kobayashi S . Transepithelial transport of chlorogenic acid, caffeic acid, and their colonic metabolites in intestinal caco-2 cell monolayers. J Agric Food Chem. 2004; 52(9):2518-26. DOI: 10.1021/jf035407c. View

13.

Ho Y, Chen W, Chi T, Chien C, Lee A, Chiu H . Caffeic acid phenethyl amide improves glucose homeostasis and attenuates the progression of vascular dysfunction in Streptozotocin-induced diabetic rats. Cardiovasc Diabetol. 2013; 12:99. PMC: 3706244. DOI: 10.1186/1475-2840-12-99. View

14.

Kamil Burgazli M, Aydogdu N, Rafiq A, Mericliler M, Chasan R, Erdogan A . Effects of caffeic acid phenethyl ester (CAPE) on membrane potential and intracellular calcium in human endothelial cells. Eur Rev Med Pharmacol Sci. 2013; 17(6):720-8. View

15.

Feng Y, Lu Y, Xu P, Long Y, Wu W, Li W . Caffeic acid phenethyl ester and its related compounds limit the functional alterations of the isolated mouse brain and liver mitochondria submitted to in vitro anoxia-reoxygenation: relationship to their antioxidant activities. Biochim Biophys Acta. 2008; 1780(4):659-72. DOI: 10.1016/j.bbagen.2008.01.002. View

16.

Konishi Y, Hitomi Y, Yoshioka E . Intestinal absorption of p-coumaric and gallic acids in rats after oral administration. J Agric Food Chem. 2004; 52(9):2527-32. DOI: 10.1021/jf035366k. View

17.

Teke Z, Birol Bostanci E, Yenisey C, Kelten E, Sacar M, Simsek N . Caffeic acid phenethyl ester prevents detrimental effects of remote ischemia-reperfusion injury on healing of colonic anastomoses. J Invest Surg. 2012; 26(1):16-29. DOI: 10.3109/08941939.2012.687434. View

18.

Ince H, Kandemir E, Bagci C, Gulec M, Akyol O . The effect of caffeic acid phenethyl ester on short-term acute myocardial ischemia. Med Sci Monit. 2006; 12(5):BR187-93. View

19.

Ozer M, Parlakpinar H, Cigremis Y, Ucar M, Vardi N, Acet A . Ischemia-reperfusion leads to depletion of glutathione content and augmentation of malondialdehyde production in the rat heart from overproduction of oxidants: can caffeic acid phenethyl ester (CAPE) protect the heart?. Mol Cell Biochem. 2005; 273(1-2):169-75. DOI: 10.1007/s11010-005-0551-8. View

20.

Wang L, Lin Y, Liang Y, Yang Y, Lee J, Yu H . The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells. BMC Immunol. 2009; 10:39. PMC: 2724478. DOI: 10.1186/1471-2172-10-39. View