The edaravone and 3-n-butylphthalide ring-opening derivative lob effectively attenuates cerebral ischemia injury in rats

• Published in: 中国药理学报：英文版 no. 8; pp. 917 - 927
• Main Author: Kai HUA Xiao SHENG Ting-ting LI Lin-na WANG Yi-hua ZHANG Zhang-jian HUANG Hui JI
• Format: Journal Article
• Language: English
• Published: 2015
• Subjects: LOB; SD大鼠; 依达拉奉; 局灶性脑缺血; 开环; 脑损伤; 苯酞; 衍生物
• ISSN: 1671-4083; 1745-7254

Aim： Compound lob is a hybrid molecule of edaravone and a ring-opening derivative of 3-n-butylphthalide （NBP）. The aim of this study was to examine the effects of compound lOb on brain damage in rats after focal cerebral ischemia. Methods： SD rats were subjected to 2-h-middle cerebral artery occlusion （MCAO）. At the onset of reperfusion, the rats were orally treated with NBP （60 mg/kg）, edaravone （3 mg/kg）, NBP （60 mg/kg）＋edaravone （3 mg/kg）, or compound lOb （70, 140 mg/kg）. The infarct volume, motor behavior deficits, brain water content, histopathological alterations, and activity of GSH, SOD, and MDA were analyzed 24 h after reperfusion. The levels of relevant proteins in the ipsilateral striatum were examined using immunoblotting. Results： Administration of compound lob （70 or 140 mg/kg） significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound lob were more pronounced compared to NBP, edaravone or NBP＋edaravone. Furthermore, compound lob significantly upregulated the protein levels of the cytoprotective molecules Bcl-2, HO-1, Nrf2, Trx, P-NF-κB p65, and IκB-α, while decreasing the expression of Bax, caspase 3, caspase 9, Txnip, NF-κB p65, and P-IκB-α. Conclusion： Oral administration of compound lob effectively attenuates rat cerebral ischemia injury.