Neuroprotection and underlying mechanisms of oxymatrine in cerebral ischemia of rats.
OBJECTIVE
Oxymatrine, extracted from a traditional Chinese herb, Sophora flavescens Ait, has shown a variety of pharmacological actions. Recently, we have proved that oxymatrine protected brain from ischemic damage. However, little is known about the exact mechanisms of this effect. This study is to investigate the potential neuroprotection of oxymatrine and explore the underlying mechanisms.


METHODS
Male Sprague-Dawley rats were subjected to acute permanent middle cerebral artery occlusion (MCAO). Oxymatrine was administered immediately after cerebral ischemia. At 24 hours after MCAO, brain water content and infarct volume were measured. The expression of 12/15-lipoxygenase (12/15-LOX), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated p38 MAPK (phospho-p38 MAPK), and cytosolic phospholipase A2 (cPLA2) was measured by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
Compared with MCAO group, oxymatrine dramatically reduced brain water content (P<0.05) and infarct volume (P<0.05). Consistent with these indices, the overexpressions of 12/15-LOX, phospho-p38 MAPK, and cPLA2 were significantly decreased in oxymatrine group. But the expression of p38 MAPK was not affected at the mRNA level.


CONCLUSIONS
Oxymatrine protected the brain from damage caused by MCAO; this effect may be through down-regulation of 12/15-LOX, phospho-p38 MAPK, and cPLA2, but not through down-regulation of p38 MAPK.
Cui
Lili
L
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, China.
Zhang
Xiangjian
X
Yang
Rui
R
Wang
Lina
L
Liu
Lingling
L
Li
Min
M
Du
Wei
W
D000470:Alkaloids / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D054510:Phospholipases A2, Cytosolic / Q000235:genetics / Q000378:metabolism; D011807:Quinolizines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000093842:Matrines
D000470:Alkaloids; D001093:Arachidonate 15-Lipoxygenase; D018696:Neuroprotective Agents; D054510:Phospholipases A2, Cytosolic; D011807:Quinolizines; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; C037573:oxymatrine; D000093842:Matrines