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