Neuroprotective effect of Smilacis chinae rhizome on NMDA-induced neurotoxicity in vitro and focal cerebral ischemia in vivo.
Previous work has shown that the Smilacis chinae rhizome (SCR) markedly inhibits amyloid beta protein (25-35)-induced neuronal cell damage in cultured rat cortical neurons. The present study was conducted to further verify the neuroprotective effect of SCR on excitotoxic and cerebral ischemic injury using both in vitro and in vivo studies. Exposure of cultured cortical neurons to 1 mM N-methyl-D-aspartate (NMDA) for 12 h induced neuronal cell death. SCR (10 and 50 microg/ml) inhibited NMDA-induced neuronal death, elevation of intracellular calcium ([Ca(2+)](i)), and generation of reactive oxygen species (ROS) in primary cultures of rat cortical neurons. In vivo, SCR prevented cerebral ischemic injury induced by 3-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct was significantly reduced in rats that received SCR (30 and 50 mg/kg, orally), with a corresponding improvement in neurological function. Moreover, SCR treatment significantly decreased the histological changes observed following ischemia. Oxyresveratrol and resveratrol isolated from SCR also inhibited NMDA-induced neuronal death, increase in [Ca(2+)](i), and ROS generation in cultured cortical neurons, suggesting that the neuroprotective effect of SCR may be attributable to these compounds. Taken together, these results suggest that the neuroprotective effect of SCR against focal cerebral ischemic injury is due to its anti-excitotoxic effects and that SCR may have a therapeutic role in neurodegenerative diseases such as stroke.
Ban
Ju Yeon
JY
College of Veterinary Medicine, Chungbuk National University,Cheongju, Chungbuk, Korea.
Cho
Soon Ock
SO
Choi
Sun-Ha
SH
Ju
Hyun Soo
HS
Kim
Ju Yeon
JY
Bae
KiHwan
K
Song
Kyung-Sik
KS
Seong
Yeon Hee
YH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D028321:Plant Preparations / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000077185:Resveratrol; D027343:Rhizome; D032281:Smilax / Q000737:chemistry; D013267:Stilbenes / Q000302:isolation & purification / Q000494:pharmacology; D013997:Time Factors
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D010936:Plant Extracts; D028321:Plant Preparations; D017382:Reactive Oxygen Species; D013267:Stilbenes; C034912:puag-haad; D016202:N-Methylaspartate; D000077185:Resveratrol; D002118:Calcium