Neuroprotective efficacy and therapeutic window of Forsythoside B: in a rat model of cerebral ischemia and reperfusion injury.
The present study was to investigate the neuroprotective efficacy and mechanism of Forsythoside B. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 1 h followed by reperfusion for 23 h. Rats received an intravenous bolus injection of Forsythoside B at 15 min after reperfusion. The results showed that Forsythoside B at doses higher than 8 mg/kg produced a significant neuroprotective potential in cerebral ischemia and reperfusion rats. Forsythoside B (20 mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 1 h, 3 h and 5 h after cerebral ischemia and reperfusion. Forsythoside B 20 mg/kg attenuated histopathological damage as demonstrated by smaller brain infarct size and brain edema, decreased cerebral Evans blue extravasation and myeloperoxidase (MPO) activity, inhibited cerebral phosphor-IkappaB-alpha and nuclear transcription factors kappaB (NF-kappaB) expression. Meanwhile, NF-kappaB expression with immunohistochemical staining was reduced, while circulating polymorphonuclear leukocytes was increased. All of these findings suggested that Forsythoside B exerted potent neuroprotective effects with a favorable therapeutic time-window, reduce of cerebral ischemia and reperfusion injury degree, attenuating blood-brain barrier (BBB) breakdown, and its protective effects may be due to inhibition of inflammatory response.
Jiang
Wang-Lin
WL
School of Pharmacy, Yantai University, 32# Qingquan Road, Laishan District, Yantai 264003, PR China.
Tian
Jing-Wei
JW
Fu
Feng-hua
FH
Zhu
Hai-Bo
HB
Hou
Jian
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D034961:Antigens, Nuclear / Q000378:metabolism; D020520:Brain Infarction / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D004195:Disease Models, Animal; D005070:Evans Blue / Q000378:metabolism; D005119:Extravasation of Diagnostic and Therapeutic Materials; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D006027:Glycosides / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000893:Anti-Inflammatory Agents; D034961:Antigens, Nuclear; D002109:Caffeic Acids; D005960:Glucosides; D006027:Glycosides; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C546339:Rbfox3 protein, rat; C552409:forsythoside B; D005070:Evans Blue; D009195:Peroxidase