title: 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.
authors.affiliation: Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), 14801-902 Araraquara, SP, Brazil.
authors.forename: Luana Chiquetto
authors.initials: LC
authors.lastname: Paracatu
authors.affiliation: Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), 14801-902 Araraquara, SP, Brazil.
authors.forename: Carolina Maria Quinello Gomes
authors.initials: CM
authors.lastname: Faria
authors.affiliation: Department of Pediatrics, Medical School, University of São Paulo, 05403-900 São Paulo, SP, Brazil.
authors.forename: Camila
authors.identifier: 0000-0002-0056-7205
authors.initials: C
authors.lastname: Quinello
authors.affiliation: Department of Pediatrics, Medical School, University of São Paulo, 05403-900 São Paulo, SP, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Rennó
authors.affiliation: Department of Pediatrics, Medical School, University of São Paulo, 05403-900 São Paulo, SP, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Palmeira
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), 14800-900 Araraquara, SP, Brazil.
authors.forename: Maria Luiza
authors.identifier: 0000-0002-0559-8502
authors.initials: ML
authors.lastname: Zeraik
authors.affiliation: Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), 14801-902 Araraquara, SP, Brazil.
authors.forename: Luiz Marcos
authors.initials: LM
authors.lastname: da Fonseca
authors.affiliation: Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), 14801-902 Araraquara, SP, Brazil ; Department of Chemistry, Faculty of Sciences, São Paulo State University (UNESP), 17033-360 Bauru, SP, Brazil.
authors.forename: Valdecir Farias
authors.initials: VF
authors.lastname: Ximenes