Crambescidin 800, a pentacyclic guanidine alkaloid, protects a mouse hippocampal cell line against glutamate-induced oxidative stress

Abstract

Oxidative stress is implicated in the pathogenesis of neuronal degenerative diseases. In our search for protective substances against glutamate-induced oxidative stress using mouse hippocampal cell line HT22, we have isolated crambescidin 800, a pentacyclic guanidine alkaloid, from the Indonesian marine sponge, Monanchora ungiculata. Crambescidin 800 (1) protected HT22 cells against glutamate-induced oxidative toxicity at 0.06 μM (EC50) concentration. Crambescidin 800 (1) also protected HT22 and neuroblastoma cells from the oxidative stress induced by a hypoxic condition or nitric oxide (NO). Crambescidin 800 (1) showed no effect on the depletion of intracellular glutathione (GSH) of HT22 cells induced by glutamate, and production of reactive oxygen species (ROS) and activation of mitogen-activated protein kinase (MAPK) were inhibited only by the high concentration (1 μM) of 1.