Cardiovascular Effects of Caffeic Acid and Its Derivatives: A Comprehensive Review
Caffeic acid (CA) is a hydroxycinnamic acid that belongs to the phenolic acid family of polyphenols. It is the main hydroxycinnamic acid present in the human diet, with the highest content being found in blueberries, kiwis, plums, cherries, and apples, although also present in cereals, carrots, salad, eggplants, cabbage, artichoke, and coffee. Besides foodstuffs, CA is also present in propolis, a resinous mixture created by honeybees from different botanical sources and a natural product that has been used in folk medicine for many centuries . Caffeic acid phenethyl ester (CAPE) is a naturally occurring derivative of CA and is also prevalent in propolis, mainly in the poplar variety, made from resinous exudates of buds and young leaves of different Populus species, especially Populus nigra L. CAPE is the single and most widely studied of all the individual constituents of propolis and is currently thought responsible for most of the poplar variety’s strong antioxidant activity . Besides Populus species, CAPE has been identified only in a few other botanical sources . In the last few decades, much interest has been shown in exploring the biological properties of CA, CAPE, and closely related derivatives, mainly synthetic ones. These compounds are known to display antioxidant, anti-inflammatory , immunomodulatory, cytostatic , antibacterial, and antiviral properties. Besides these important activities, CA and its derivatives have shown a very high potential for treating and preventing cardiovascular diseases in preclinical studies. Their useful biological activities, coupled with favorable safety profiles, make them good candidates for clinical studies. The aim of this paper is to provide a comprehensive and up-to-date review of the main cardiovascular actions attributed to CA and its derivatives both in vitro and in vivo in order to highlight their main therapeutic potentials.
Caffeic acid and its derivatives display major actions on the cardiovascular system. Several compounds (CA, CAPE, and CAPA) display relevant vasorelaxant activity and attributed to diverse cellular mechanisms. Besides their vasorelaxant activity, CA and CAPE also lower heart rate and suppress the renin-angiotensin-aldosterone axis, which explains their blood pressure-lowering activity. However, there is a notable shortage of in vivo studies that center on exploring effects on perfusion. Furthermore, the pharmacokinetic profile of some CA derivatives is still lacking in both animals and human subjects, which should prompt further studies. Caffeic acid phenethyl ester is the most studied compound, and shows marked anti-atherosclerotic and anti-angiogenic effects, as well as protection against ischemia/reperfusion lesions, which is why it is the one with the highest potential highest potential for translation into clinical medicine.
