Total bakkenolides protects neurons against cerebral ischemic injury through inhibition of nuclear factor-κB activation.

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.

• Authors: Qian Jiang, Yu-Ye Xia, Jian-Ming He, Mei-Li Guo, Run-Ping Li
• Journal: CNS & neurological disorders drug targets (CNS Neurol Disord Drug Targets) Vol. 13 Issue 5 Pg. 874-84 ( 2014) ISSN: 1996-3181 [Electronic] United Arab Emirates
• PMID: 24040794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Neuroprotective Agents
• Sesquiterpenes

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects)
• Brain Infarction (etiology, prevention & control)
• Cells, Cultured
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hippocampus (cytology)
• In Situ Nick-End Labeling
• Ischemic Attack, Transient (complications, prevention & control)
• Male
• NF-kappa B (metabolism)
• Nervous System Diseases (drug therapy, etiology)
• Neurons (drug effects)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Sesquiterpenes (chemistry, pharmacology, therapeutic use)