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.
CNS & Neurological Disorders - Drug Targets
Title:Total Bakkenolides Protects Neurons Against Cerebral Ischemic Injury Through Inhibition of Nuclear Factor-κB Activation
Volume: 13 Issue: 5
Author(s): Qian Jiang, Yu-Ye Xia, Jian-Ming He, Mei-li Guo and Run-Ping Li
Affiliation:
Keywords: Total bakkenolides; cerebral ischemia; neuroprotection; mechanism; nuclear factor-κB.
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.
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Cite this article as:
Jiang Qian, Xia Yu-Ye, He Jian-Ming, Guo Mei-li and Li Run-Ping, Total Bakkenolides Protects Neurons Against Cerebral Ischemic Injury Through Inhibition of Nuclear Factor-κB Activation, CNS & Neurological Disorders - Drug Targets 2014; 13 (5) . https://dx.doi.org/10.2174/18715273113129990104
DOI https://dx.doi.org/10.2174/18715273113129990104 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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