RESUMEN

Nordihydroguaiaretic acid (NDGA) and rosmarinic acid (RA), phenolic compounds found in various plants and functional foods, have known antioxidant and anti-inflammatory properties. In the present study, we comparatively investigated the importance of hydrophobicity and oxidisability of NDGA and RA, regarding their antioxidant and pharmacological activities. Using a panel of cell-free antioxidant protocols, including electrochemical measurements, we demonstrated that the anti-radical capacities of RA and NDGA were similar. However, the relative capacity of NDGA as an inhibitor of NADPH oxidase (ex vivo assays) was significantly higher compared to RA. The inhibitory effect on NADPH oxidase was not related to simple scavengers of superoxide anions, as confirmed by oxygen consumption by the activated neutrophils. The higher hydrophobicity of NDGA was also a determinant for the higher efficacy of NDGA regarding the inhibition of the release of hypochlorous acid by PMA-activated neutrophil and cytokine (TNF-α and IL-10) production by Staphylococcus aureus-stimulated peripheral blood mononuclear cells. In conclusion, although there have been extensive studies about the pharmacological properties of NDGA, our study showed, for the first time, the importance not only of its antioxidant activity, but also its hydrophobicity as a crucial factor for pharmacological action.

Asunto(s)

Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Masoprocol/farmacología , NADPH Oxidasas/antagonistas & inhibidores , Neutrófilos/efectos de los fármacos , Adulto , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/química , Antioxidantes/efectos adversos , Antioxidantes/química , Células Cultivadas , Cinamatos/efectos adversos , Cinamatos/química , Cinamatos/farmacología , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Depsidos/efectos adversos , Depsidos/química , Depsidos/farmacología , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/química , Fármacos Hematológicos/efectos adversos , Fármacos Hematológicos/química , Fármacos Hematológicos/farmacología , Hemólisis/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ácido Hipocloroso/antagonistas & inhibidores , Ácido Hipocloroso/metabolismo , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Activación de Linfocitos/efectos de los fármacos , Masoprocol/efectos adversos , Masoprocol/química , NADPH Oxidasas/metabolismo , Activación Neutrófila/efectos de los fármacos , Neutrófilos/citología , Neutrófilos/inmunología , Neutrófilos/metabolismo , Concentración Osmolar , Adulto Joven , Ácido Rosmarínico

RESUMEN

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.