Antineuroinflammatory polyketide plakortide N from the Brazilian marine sponge Plakortis angulospiculatus

Abstract

Involvement of brain microglia (BMΦ) in neuroinflammation has been hypothesized (Mayer AMS, MEDICINA 58:377, 1998; Mayer AMS et al., SHOCK 11: 180, 1999). We have reported marine chemicals as a potential source of antineuroinflammatory compounds (Mayer et al. BioMedCentral Pharmacology 5:6, 2005) using Escherichia coli lipopolysaccharide (LPS)‐activated BMΦ as our in vitro model (Mayer AMS et al., SHOCK 11:180, 1999). The purpose of this investigation was to study the effect of several polyketides isolated from the marine sponge Plakortis angulospiculatus on phorbol ester (PMA)‐stimulated thromboxane B2 (TXB2) and superoxide anion (O2−) generation from E. coli LPS‐activated rat BMΦ O2− was determined by superoxide dismutase‐inhibitable reduction of ferricytochrome C and TXB2 using commercially available immunoassays. Only plakortide N potently inhibited TXB2 (IC50=0.93μM) but not O2− (IC50 >10μM), with low lactic dehydrogenase release (LDH50>10μM). Because LDH release was low, our current data suggests that the significant inhibitory effect of plakortide N on BMΦ TXB2 release was pharmacologic rather than toxic in nature, although the molecular mechanism of inhibition remains undetermined at this time. (Supported by American Society of Pharmacognosy 1998 Research Starter Grant, NIH grant CA 67786 and FAPESP grants 01/03095‐0 and 05/60175‐2 to RGB and Midwestern University to AMM).TOTAL