Neuroprotective efficacy and therapeutic window of Forsythoside B: in a rat model of cerebral ischemia and reperfusion injury

Wang-Lin Jiang, Jing-Wei Tian, Feng-hua Fu, Hai-Bo Zhu, Jian Hou
European Journal of Pharmacology 2010 August 25, 640 (1): 75-81
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.


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