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Total Bakkenolides Protects Neurons Against Cerebral Ischemic Injury Through Inhibition of Nuclear Factor-κB Activation

[ Vol. 13 , Issue. 5 ]

Author(s):

Qian Jiang, Yu-Ye Xia, Jian-Ming He, Mei-li Guo and Run-Ping Li   Pages 874 - 884 ( 11 )

Abstract:


Total bakkenolides is the major component of the rhizome of Petasites trichinous Franch.. In this study, we investigated its neuroprotective effects in a rat transient focal cerebral ischemia-reperfusion model, and in an in vitro cerebral ischemia model, oxygen-glucose deprivation of cultured nerve cells. Oral administration of total bakkenolides immediately after reperfusion at doses of 5, 10 and 20 mg/kg markedly reduced brain infarct volume and neurological deficits. Total bakkenolides significantly attenuated cell death and apoptosis in primarily cultured neurons subject to 1-h hypoxia followed by 24-h reoxygenation. Morphologic observations directly confirmed its protective effect on neurons. We also demonstrated that total bakkenolides could inhibit nuclear factor-κB (NF-κB) activation by blocking the classic activation pathway through suppression of phosphorylation of IκB-kinase complex, NF-κB/p65 and inhibitor protein IκB, inducing nuclear translocation of NF-κB/p65 and degradation of IκB. Further, total bakkenolides inhibited the activation of Akt and the extracellular signal-regulated kinase 1/2, two important upstream activators of NF-κB. In conclusion, our results provide a strong pharmacological basis for further understanding the potential therapeutic role of total bakkenolides in cerebral ischemic disease and shed new light on its neuroprotective mechanism.

Keywords:

Total bakkenolides; cerebral ischemia; neuroprotection; mechanism; nuclear factor-κB.

Affiliation:

(Mei-Li Guo) NO. 325, Guohe Road, Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.



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