The characteristics of therapeutic effect of pinocembrin in transient global brain ischemia/reperfusion rats.
OBJECTIVE
The therapeutic effect of pinocembrin, together with the therapeutic time window, in the transient global cerebral ischemia/reperfusion (I/R) rats was investigated.


METHODS
Adult male Sprague-Dawley rats were subjected to global cerebral ischemia for 20 min by four-vessel occlusion. Pinocembrin (1 and 5mg/kg) was administrated intravenously 30 min before ischemia and 30 min, 2h, 6h after reperfusion, respectively. Neurological scores, brain edema and histological examination by Nissl staining were employed to assess the neuronal injury after ischemia and the neuroprotection by pinocembrin. The activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and the content of malondialdehyde (MDA) in brain tissue were tested by colorimetric assays. Alterations of neurotransmitters were determined by a high performance liquid chromatography-electrochemical method.


RESULTS
Pinocembrin significantly ameliorated neurological deficits and brain edema, and alleviated the degree of hippocampal neuronal loss at 24h after global cerebral I/R with a broad therapeutic time window. It was found that treatment with pinocembrin reduced the compensatory increase of SOD activity and decreased the MDA level and MPO activity in a dose-dependent manner. The metabolic balance between excitatory and inhibitory amino acids was modulated by pinocembrin treatment.


CONCLUSIONS
These findings suggest that pinocembrin provides neuroprotection against global cerebral ischemic injury with a wide therapeutic time window, which may be attributed to its antioxidative, antiinflammatory and antiexcitotoxic effects.
National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.
Li-li
LL
Shi
Bai-nian
BN
Chen
Mei
M
Gao
Heng-ai
HA
Zhang
Yan-jing
YJ
Li
Li
L
Wang
Guan-hua
GH
Du
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001929:Brain Edema / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
D000596:Amino Acids; D044950:Flavanones; D018696:Neuroprotective Agents; C016063:pinocembrin