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