Falcarindiol inhibits nitric oxide-mediated neuronal death in lipopolysaccharide-treated organotypic hippocampal cultures.

Excessive nitric oxide (NO) release from activated microglia has a predominant role in neuronal death. This study investigated the effect of falcarindiol, which was isolated from Cnidium officinale Makino, on the NO-mediated neuronal death in lipopolysaccharide (LPS)-treated organotypic hippocampal cultures. Falcarindiol dose-dependently reduced inducible NO synthase (iNOS)-mediated NO production without cytotoxic effects on LPS-activated BV-2 and microglia. Predictably, falcarindiol inhibited neuronal death by reducing NO production in the LPS-treated organotypic hippocampal cultures. N-monomethyl-L-arginine (NMMA), an iNOS inhibitor, also inhibited neuronal death at 500 microM. In contrast, massive neuronal death was induced by excessive NO production in the LPS-treated alone cultures. These results suggest that excessive NO production plays an important role in the neurotoxic effect, and falcarindiol is a potential inhibitor in NO-mediated neuronal death.