Caffeic Acid Phenethyl Ester: Consequences of Its Hydrophobicity in the Oxidative Functions and Cytokine Release by Leukocytes

Abstract

Numerous anti-inflammatory properties have been attributed to caffeic acid phenethyl ester (CAPE), an active component of propolis. NADPH oxidases are multienzymatic complexes involved in many inflammatory diseases. Here, we studied the importance of the CAPE hydrophobicity on cell-free antioxidant capacity, inhibition of the NADPH oxidase and hypochlorous acid production, and release of TNF-α and IL-10 by activated leukocytes. The comparison was made with the related, but less hydrophobic, caffeic and chlorogenic acids. Cell-free studies such as superoxide anion scavenging assay, triene degradation, and anodic peak potential (E pa) measurements showed that the alterations in the hydrophobicity did not provoke significant changes in the oxidation potential and antiradical potency of the tested compounds. However, only CAPE was able to inhibit the production of superoxide anion by activated leukocytes. The inhibition of the NADPH oxidase resulted in the blockage of production of hypochlorous acid. Similarly, CAPE was the more effective inhibitor of the release of TNF-α and IL-10 by Staphylococcus aureus stimulated cells. In conclusion, the presence of the catechol moiety and the higher hydrophobicity were essential for the biological effects. Considering the involvement of NADPH oxidases in the genesis and progression of inflammatory diseases, CAPE should be considered as a promising anti-inflammatory drug.

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

“…Its partition coefficient (log P ) differs between publications, ranging between 1.0 and 1.3 ( Wu W.M. et al, 2007 ; Kudugunti et al, 2010 ; Paracatu et al, 2014 ). In its free form, CA is absorbed in the gastrointestinal tract through monocarboxylic acid transporters ( Konishi and Kobayashi, 2004 ; Konishi et al, 2004 ) and, to a lesser extent, through transepithelial flux ( Konishi et al, 2003 ).…”

“…It is lipophilic with logP values differing between publications, ranging between 3.2 and 13.8 ( Koltuksuz et al, 1999 ; Wu W.M. et al, 2007 ; Paracatu et al, 2014 ), which allows it to cross the blood-brain barrier in rats ( Wei et al, 2004 ; Barros Silva et al, 2013 ). As the isolation and purification of CAPE from natural sources are expensive, low-yielding and time-consuming, several chemical and enzymatic synthetic methods have been developed ( Bankova et al, 2018 ).…”

Antioxidant and anti-inflammatory effects of biotechnologically transformed propolis

“…Blind absorbance was removed from the absorbance values by blind preparation without propolis. The percent inhibition of superoxide formation according to the propolis control sample was calculated as a percentage (Paracatu et al, ).…”

Synthesis and evaluation of the potential deleterious effects of ZnO nanomaterials (nanoneedles and nanoflowers) on blood components, including albumin, erythrocytes and human isolated primary neutrophils

“…The supernatant was discarded and the neutrophils were washed twice with PBS buffer (700g, 10 min, 25°C). The neutrophils were counted and suspended in PBS supplemented with 0.5 mM CaCl 2 , 0.5 mM MgCl 2 and 1 mg/mL glucose (Paracatu et al 2014).…”