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.
Kim
Jeong Min
JM
Department of Herbal Pharmacology, Graduate School of East-West Medical Science, Kyunghee University, Seoul, Korea.
Lee
Pyeongjae
P
Son
Dongwook
D
Kim
Hocheol
H
Kim
Sun Yeou
SY
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D053280:Diynes; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005233:Fatty Alcohols / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D019323:omega-N-Methylarginine / Q000494:pharmacology
D053280:Diynes; D004791:Enzyme Inhibitors; D005233:Fatty Alcohols; D008070:Lipopolysaccharides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C034379:falcarindiol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat