Influence of OAS‐1000 on mediators of inflammation

Abstract . OAS‐1000 is a semisynthetic derivative of pseudopterosine A, isolated from sea whip ( Pseudopterogorgia elizabethae ), that has been shown to have topical anti‐inflammatory activity. The purpose of this research was to investigate OAS‐1000 for potential use as an anti‐inflammatory agent for topical oral application, and to begin to investigate a mechanism of action. OAS‐1000 was therefore evaluated as an inhibitor of 4 enzymes of the arachidonic acid metabolic pathways (prostaglandin G/H synthase I (PGHS‐1, COX‐1), prostaglandin G/H synthase II (PGHS‐2, COX‐2), arachidonate 5‐lipoxygenase (5‐LOX), and arachidonate 15‐lipoxygenase (15‐LOX)). It was found that OAS‐1000 inhibits PGHS‐1 activity with an IC‐50 value of 80.3 μM, but had much less activity versus PGHS‐2 enzyme and no activity versus the 15‐LOX enzyme. 5‐LOX activity showed some inhibition, but only at a high OAS‐1000 concentrations. Additionally, OAS‐1000 was tested for it's ability inhibit 1 ng/ml IL‐1b stimulated PGE2 production in a cell culture system. Inhibition of 46% was seen at an OAS‐1000 concentration of 22.4 μM. Taken together, these experiments suggest that at least some of the topical anti‐inflammatory activity of OAS‐1000 may be attributed to inhibition of the arachidonic acid metabolites that have been shown to be important in inflammation and tissue destruction.