Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms.
In the present study we report the preventive effect of apocynin, an active constituent of the Himalayan herb Picrorhiza kurrooa, on cyclooxygenase-2 (Cox-2) synthesis and activity in human adherent monocytes exposed to serum treated zymosan (STZ) and phorbol myristate acetate (PMA). Apocynin markedly decreases the intracellular reduced/oxidized glutathione ratio (GSH/GSSG) and prevents nuclear factor-kappaB (NF-kappaB) activation in stimulated monocytes. Moreover, it reduces intracellular reactive oxygen species (ROS) generation, NADPH oxidase activity in monocyte homogenates and translocation of p47phox subunit in monocyte membranes. p47phox levels are also reduced in lysates of apocynin-treated monocytes. The inhibition of Cox-2 by apocynin is completely abrogated by GSH provision. Results from this study indicate that apocynin inhibits Cox-2 synthesis and activity induced in monocytes by an increased oxidative tone and provide an explanation for the protective effect exerted by this compound in numerous cell and animal models of inflammation. Attenuation of NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of NF-kappaB activation are highlighted as the molecular mechanisms responsible for Cox-2 inhibition.
Barbieri
Silvia S
SS
E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of Milan, Italy.
Cavalca
Viviana
V
Eligini
Sonia
S
Brambilla
Marta
M
Caiani
Alessia
A
Tremoli
Elena
E
Colli
Susanna
S
D000098:Acetophenones / Q000378:metabolism / Q000494:pharmacology*; D000906:Antibodies / Q000737:chemistry; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D020033:Protein Isoforms; D021381:Protein Transport; D017382:Reactive Oxygen Species; D013929:Thromboxane B2 / Q000378:metabolism; D013997:Time Factors
D000098:Acetophenones; D000906:Antibodies; D000975:Antioxidants; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D010750:Phosphoproteins; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D013929:Thromboxane B2; C056165:acetovanillone; D009195:Peroxidase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D005978:Glutathione; D015232:Dinoprostone; D010100:Oxygen