Influence of Dimerization of Apocynin on Its Effects in Experimental Colitis

Abstract

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 PGE 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.

Naturally Occurring Phenols Modulate Vegetative Growth and Deoxynivalenol Biosynthesis in Fusarium graminearum

“…Apocynin, known for its antioxidant, antimicrobial, and anti-inflammatory activities, ,, displayed a concentration-dependent inhibitory effect on trichothecene biosynthesis. In a previous modeling approach, Pani et al considered the trichodiene synthase protein TRI5 as a hypothetical target for phenolic inhibitors of trichothecene biosynthesis, providing an estimation of F.…”

Apocynin, an Inhibitor of the Nadph Oxidase Complex

“…The oxidant species can act by modifying the redox state of DNA, protein, or lipid molecules (Schieber and Chandel, 2014) and play a central role in the development of chronic pathologies and various health complications. As an example, one can cite vascular problems (Munzel et al, (Schieber and Chandel, 2014;Marín, 2017;Rhaman, 2017). Among the species responsible for causing this damage are the superoxide anion produced from molecular oxygen and the NADPH multienzyme system (Chan et al, 2009).…”

“…Also, both compounds were effective in increasing NO• and also decreased RO levels in endothelial cells. In the study reported by Marín et al (2017), diapocynin was chemically synthesized and tested in macrophages stimulated by lipopolysaccharide in an ulcerative colitis model. In this case, diapocynin showed inhibitory activity similar to apocynin, but more expressive.…”

“…The results reported suggest that oxidation products, or transient species generated during the oxidation of apocynin, prevent migration of the p47phox component to the membrane, avoiding the assembly of NADPH. In this way, the operation of this complex is prevented (Dranka et al, 2013, Potje, 2017Pérez et al, 2017;Marín, 2017).…”

Methyl divanillate: redox properties and binding affinity with albumin of an antioxidant and potential NADPH oxidase inhibitor

“…7,10,[30][31][32] Homodimers of these methoxy-substituted catechols also have biological effects and, sometimes, superior to their precursors, as have been demonstrated to diapocynin, and divanillin. 10,11,33,34 Usually, the antioxidative efficacy of these dimers is increased.…”