Mechanisms of the Anti‐inflammatory Action of Apocynin

Abstract

Apocynin is a natural compound that has been used for centuries to treat a number of diseases, including asthma. We have shown that apocynin inhibits production of numerous cytokines (CCL2, CCL7, GM‐CSF, IL‐8, and IL‐6) in airway epithelial cells stimulated with TNF‐α. The mechanism of apocynin action is unclear; it can act as an anti‐oxidant, but has also been proposed to prevent generation of reactive oxygen species by inhibition of the p47 subunit of the NADPH oxidase. Using 15 amino acid synthetic peptides corresponding to cysteine‐containing regions of p47, we have shown by mass spectrometry that apocynin induces intermolecular disulfide bond formation. Similarly, apocynin induced the disulfide‐linked oligomerization of purified p47 protein. Furthermore, apocynin treatment altered the gel mobility of another NADPH oxidase component, Noxo1 in human airway cells. These effects do not seem to be specific, as apocynin also oxidizes cysteines in albumin and tubulin. We propose that apocynin can act as both an oxidant and anti‐oxidant, and can exert effects on cellular proteins in the inflammatory response. This work was supported by internal funding at the Penn State College of Medicine.