“Mechanisms and applications of non-steroidal anti-inflammatory drugs in the chemoprevention of cancer.”
Mutat Res. 2003;523-524:137-144.
The metabolism of arachidonic acid in cell membranes plays an important role in the inflammatory response by generating potent chemical messengers known as eicosanoids.
“Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase.”
Membrane phospholipids are hydrolyzed by phospholipase A2 (PLA2), releasing arachidonic acid, which may be metabolized by cyclooxygenases (COX) to form prostaglandins and thromboxanes, or by lipoxygenases (LOX) to form leukotrienes. Curcumin has been found to inhibit PLA2, COX-2, and 5-LOX activities in cultured cells
“Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex.”
Although curcumin inhibited the catalytic activity of 5-LOX directly, it inhibited PLA2 by preventing its phosphorylation and COX-2 mainly by inhibiting its transcription. Nuclear factor-kappa B (NF-kB) is a transcription factor that binds DNA and enhances the transcription of the COX-2 gene as well as other pro-inflammatory genes, such as inducible nitric oxide synthase (iNOS). In inflammatory cells, such as macrophages, iNOS catalyzes the synthesis of nitric oxide, which can react with superoxide to form peroxynitrite, a reactive nitrogen species that can damage proteins and DNA. Curcumin has been found to inhibit NF-kB-dependent gene transcription
Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages”
Biochem Biophys Res Commun. 1995;206(2):533-540