Arctigenin protects cultured cortical neurons from glutamate-induced neurodegeneration by binding to kainate receptor.
We previously reported that arctigenin, a lignan isolated from the bark of Torreya nucifera, showed significant neuroprotective activity against glutamate-induced toxicity in primary cultured rat cortical cells. In this study, the mode of action of arctigenin was investigated using primary cultures of rat cortical cells as an in vitro system. Arctigenin significantly attenuated glutamate-induced neurotoxicity when added prior to or after an excitotoxic glutamate challenge. The lignan protected cultured neuronal cells more selectively from neurotoxicity induced by kainic acid than by N-methyl-D-aspartate. The binding of [(3)H]-kainate to its receptors was significantly inhibited by arctigenin in a competitive manner. Furthermore, arctigenin directly scavenged free radicals generated by excess glutamate and successfully reduced the level of cellular peroxide in cultured neurons. These results suggest that arctigenin exerted significant neuroprotective effects on glutamate-injured primary cultures of rat cortical cells by directly binding to kainic acid receptors and partly scavenging of free radicals.
Jang
Young P
YP
College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
Kim
So R
SR
Choi
Young H
YH
Kim
Jinwoong
J
Kim
Sang G
SG
Markelonis
George J
GJ
Oh
Tae H
TH
Kim
Young C
YC
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005663:Furans / Q000378:metabolism* / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D017705:Lignans / Q000378:metabolism* / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009410:Nerve Degeneration / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology*; D010545:Peroxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000378:metabolism*
D016166:Free Radical Scavengers; D005663:Furans; D018698:Glutamic Acid; D007608:Kainic Acid; D017705:Lignans; D016202:N-Methylaspartate; D018696:Neuroprotective Agents; D010545:Peroxides; D018092:Kainic Acid Receptors; C071942:arctigenin