Magnolol reduces glutamate-induced neuronal excitotoxicity and protects against permanent focal cerebral ischemia up to 4 hours.
Neuroprotective efficacy of magnolol, 5,5'-dially-2,2'-dihydroxydiphenyl, was investigated in a model of stroke and cultured neurons exposed to glutamate-induced excitotoxicity. Rats were subjected to permanent middle cerebral artery occlusion (pMCAO). Magnolol or vehicle was administered intraperitoneally, at 1 hr pre-insult or 1-6 hrs post-insult. Brain infarction was measured upon sacrifice. Relative to controls, animals pre-treated with magnolol (50-200 mg/kg) had significant infarct volume reductions by 30.9-37.8% and improved neurobehavioral outcomes (P<0.05, respectively). Delayed treatment with magnolol (100 mg/kg) also protected against ischemic brain damage and improved neurobehavioral scores, even when administered up to 4 hrs post-insult (P<0.05, respectively). Additionally, magnolol (0.1 µM) effectively attenuated the rises of intracellular Ca(2+) levels, [Ca(2+)](i), in cultured neurons exposed to glutamate. Consequently, magnolol (0.1-1 µM) significantly attenuated glutamate-induced cytotoxicity and cell swelling (P<0.05). Thus, magnolol offers neuroprotection against permanent focal cerebral ischemia with a therapeutic window of 4 hrs. This neuroprotection may be, partly, mediated by its ability to limit the glutamate-induced excitotoxicity.
Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Wei-Ting
WT
Lee
Miao-Hui
MH
Lin
E-Jian
EJ
Lee
Yu-Chang
YC
Hung
Shih-Huang
SH
Tai
Hung-Yi
HY
Chen
Tsung-Ying
TY
Chen
Tian-Shung
TS
Wu
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery; D007274:Injections, Intraperitoneal; D017705:Lignans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001713:Biphenyl Compounds; D017705:Lignans; D018696:Neuroprotective Agents; C005498:magnolol; D018698:Glutamic Acid; D002118:Calcium