Isoquinolinequinone Derivatives from a Marine Sponge ( sp.) Regulate Inflammation in In Vitro System of Intestine.

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (-) were isolated from the marine sponge sp. Among these, methyl -demethylrenierate () is a noble ester, whereas compounds and are new -demethyl derivatives of known isoquinolinequinones. Compound was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. -demethyl renierone () showed the highest activity, while and showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in and , and the N-formyl group in may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.