Influence of Dimerization of Apocynin on Its Effects in Experimental Colitis.
Apocynin has been widely used as an inhibitor of the nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) system and shows promise as an anti-inflammatory drug. Diapocynin, the dimeric product generated by the oxidation of apocynin in the presence of myeloperoxidase (MPO), is supposed to be its active form. In this study, diapocynin has been chemically synthesized and its activity on several inflammatory mediators in LPS-stimulated RAW 264.7 macrophages and its anti-inflammatory effect on ulcerative colitis induced by dextran sodium sulfate (DSS) in mice analyzed. We found that diapocynin showed higher inhibitory activity than apocynin. The dimer reduced ROS production, TNF-α, IL-6, and IL-1β levels and inhibited iNOS and COX-2 expression as well as decreased NO and PGE2 production induced in LPS-stimulated RAW 264.7 cells. The anti-inflammatory molecular mechanism of diapocynin was associated with the suppression of NF-κB activation. However, these results were not paralleled by in vivo studies. Oral administration of apocynin and diapocynin (100 mg/kg) three times a week exhibited similar protections against experimental inflammatory bowel disease induced by DSS; therefore, apocynin should not be considered a prodrug. However, it should be taken into account that the dimer is more potent because its dose (0.3 mmol/kg) is half that of apocynin.
['Marín|Marta|M|', 'Gimeno|Clotilde|C|', 'Giner|Rosa M|RM|', 'Ríos|José L|JL|', 'Máñez|Salvador|S|', 'Recio|Marı A C|MAC|http://orcid.org/0000-0002-1021-8703']
D000098:Acetophenones D000818:Animals D001713:Biphenyl Compounds D003092:Colitis D051546:Cyclooxygenase 2 D019281:Dimerization D006801:Humans D053583:Interleukin-1beta D015850:Interleukin-6 D008264:Macrophages D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D015394:Molecular Structure D016328:NF-kappa B D014409:Tumor Necrosis Factor-alpha
apocynin diapocynin ulcerative colitis COX-2 macrophages RAW 264.7