Abstract
Aim:
Compound 10b 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 10b 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 10b (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 10b (70 or 140 mg/kg) significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound 10b were more pronounced compared to NBP, edaravone or NBP+edaravone. Furthermore, compound 10b 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 10b effectively attenuates rat cerebral ischemia injury.
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Acknowledgements
This study was financially supported by grants from the National Natural Science Foundation of China (No 81373419) and the PhD Program Foundation of the Ministry of Education of China, China Pharmaceutical University (No 20130096110005).
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Hua, K., Sheng, X., Li, Tt. et al. The edaravone and 3-n-butylphthalide ring-opening derivative 10b effectively attenuates cerebral ischemia injury in rats. Acta Pharmacol Sin 36, 917–927 (2015). https://doi.org/10.1038/aps.2015.31
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DOI: https://doi.org/10.1038/aps.2015.31
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