Stereochemical Determination of Fistularins Isolated from the Marine Sponge and Their Regulatory Effect on Intestinal Inflammation.

By activity-guided fractionation based on inhibition of nitric oxide (NO) and prostaglandin E2 (PGE), six fistularin compounds (-) were isolated from the marine sponge (order Astrophorida). Based on stereochemical structure determination using Mosher's method, fistularin-3 was assigned as a new stereoisomer. On the basis of the stereochemistry of fistularin-3, the stereochemical homogeneity of all six compounds was established by comparing carbon and proton chemical shifts. For fistularin-1 () and -2 (), quantum calculations were performed to confirm their stereochemistry. In a co-culture system of human epithelial Caco-2 cells and THP-1 macrophages, all six isolated compounds showed potent anti-inflammatory activities. These bioactive fistularins inhibited the production of NO, PGE, TNF-α, IL-1β, and IL-6 induced by lipopolysaccharide and interferon gamma. Inducible NO synthase and cyclooxygenase-2 expression and MAPK phosphorylation were downregulated in response to the inhibition of NF-κB nuclear translocation. Among the compounds tested, fistularin-1 () and 19-deoxyfistularin-3 () showed the highest activity. These findings suggest the potential use of the marine sponge and its metabolites as pharmaceuticals for the treatment of inflammation-related diseases including inflammatory bowel disease.