Limonoids from Dictamnus dasycarpus protect against glutamate-induced toxicity in primary cultured rat cortical cells.
In our previous report, four limonoids, obacunone, limonin, fraxinellone, and calodendrolide, isolated from Dictamnus dasycarpus showed significant neuroprotective activity against glutamate toxicity in primary cultured rat cortical cells. This study investigated neuroprotective mechanism of these compounds using the same in vitro culture system. These four compounds showed significant neuroprotective activity at the concentration of 0.1 muM. They effectively inhibited calcium influx and overproduction of cellular nitric oxide and reactive oxygen species accompanied by glutamate-induced neurotoxicity. In addition, these compounds significantly preserved mitochondrial membrane potential and activities of antioxidative enzymes. Our results showed that obacunone, limonin, fraxinellone, and calodendrolide significantly protect primary culture cortical cells against glutamate-induced toxicity by preserving the antioxidant defense system. These compounds might offer potential drug development candidate for various neurodegenerative diseases involved with glutamate.
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, San 56-1, Sillim-Dong, Gwanak-Gu, Seoul 151-742, South Korea.
Jeong Seon
JS
Yoon
Hyekyung
H
Yang
Seung Hyun
SH
Kim
Sang Hyun
SH
Sung
Young Choong
YC
Kim
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D036905:Dictamnus / Q000737:chemistry*; D018698:Glutamic Acid / Q000633:toxicity*; D036701:Limonins / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D036701:Limonins; D010936:Plant Extracts; D009569:Nitric Oxide; D018698:Glutamic Acid; D002118:Calcium