15-Methoxypinusolidic acid from Biota orientalis attenuates glutamate-induced neurotoxicity in primary cultured rat cortical cells.
15-Methoxypinusolidic acid (15-MPA), a pinusolide derivative isolated from Biota orientalis (Cupressaceae) leaves prevented glutamate-induced excitotoxicity in primary cultured rat cortical cells in vitro. 15-MPA had more selectivity in protecting neurons against N-methyl-D-aspartate (NMDA)-induced neurotoxicity than that induced by kainic acid (KA). The glutamate-induced increase of intracellular calcium ([Ca2+]i) in cortical cells was effectively reduced by 15-MPA. Moreover, 15-MPA could successfully reduce the subsequent overproduction of nitric oxide (NO) and the level of cellular peroxide, and inhibit glutathione (GSH) depletion and lipid peroxidation induced by glutamate in our cultures. Collectively, these results suggested that 15-MPA attenuated glutamate-induced excitotoxicity via stabilization of [Ca2+]i homeostasis and suppression of oxidative stress possibly through the actions on the NMDA receptors.
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, San 56-1, Shillim-Dong, Gwanak-Gu, Seoul 151-742, Republic of Korea.
Kyung Ah
KA
Koo
Seung Hyun
SH
Kim
Mi Kyeong
MK
Lee
Young Choong
YC
Kim
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D029783:Thuja / Q000737:chemistry*
C464724:15-methoxypinusolidic acid; D004224:Diterpenes; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D018698:Glutamic Acid; D005978:Glutathione; D002118:Calcium