Hydrophobicity and antioxidant activity acting together for the beneficial health properties of nordihydroguaiaretic acid.
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.
Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), 14801-902, Araraquara, São Paulo, Brazil.
Luana Chiquetto
LC
Paracatu
Carolina Maria Quinello Gomes
CM
de Faria
Maria Luiza
ML
Zeraik
Camila
C
Quinello
Camila
C
Rennó
Patrícia
P
Palmeira
Luiz Marcos
LM
da Fonseca
Valdecir Farias
VF
Ximenes
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D002934:Cinnamates / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D053630:Depsides / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D006401:Hematologic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009637:Masoprocol / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009994:Osmolar Concentration; D055815:Young Adult; D000097123:Rosmarinic Acid
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D002934:Cinnamates; D016207:Cytokines; D053630:Depsides; D004791:Enzyme Inhibitors; D006401:Hematologic Agents; D006997:Hypochlorous Acid; D009637:Masoprocol; D019255:NADPH Oxidases; D000097123:Rosmarinic Acid