Abstract:
AIMS:This study was designed to examine the neuroprotective effects of bakkenolide-IIIa, a major novel compound extracted from the rhizome of P. trichinous. METHODS:Transient focal cerebral damage model in rats and oxygen-glucose deprivation (OGD) in cultured hippocampal neurons were performed. The amount of apoptotic neurons was determined using TUNEL assay. The expressions of Bcl-2, Bax, Akt, ERK1/2, IKKβ, IκBα were measured using Western blot. The nuclear translocation and activation of NF-κB was measured using a fluorescence microscope and electrophoretic mobility shift assay (EMSA). RESULTS:Bakkenolide-IIIa (4, 8, 16 mg/kg; i.g.) was administered immediately after reperfusion could reduce the brain infarct volume, and the neurological deficit, as well as a high dose of bakkenolide-IIIa, increases the 72 h survival rate in cerebrally damaged rats. In vitro data demonstrated that bakkenolide-IIIa could increase cell viability and decrease the amount of apoptotic cells in cultured primary hippocampal neurons exposed to OGD. Bakkenolide-IIIa also dose-dependently increased the ratio of Bcl-2 to Bax. These results indicated that inhibition of apoptosis partly mediated the neuroprotection of bakkenolide-IIIa. Furthermore, bakkenolide-IIIa inhibited the phosphorylation of Akt, ERK1/2, IKKβ, IκBα, and p65 in cultured hippocampal neurons exposed to OGD. Bakkenolide-IIIa not only inhibited the nuclear translocation of NF-κB in cultured neurons exposed to OGD, but also inhibited the activation of NF-κB in peri-infarct area in cerebrally damaged rats. CONCLUSION:Collectively, our findings indicated that bakkenolide-IIIa protects against cerebral damage by inhibiting AKT and ERK1/2 activation and inactivated NF-κB signaling.
journal_name
CNS Neurosci Therjournal_title
CNS neuroscience & therapeuticsauthors
Jiang Q,Li RP,Tang Y,Wang YQ,Liu C,Guo MLdoi
10.1111/cns.12470subject
Has Abstractpub_date
2015-12-01 00:00:00pages
943-52issue
12eissn
1755-5930issn
1755-5949journal_volume
21pub_type
杂志文章abstract:INTRODUCTION:Patients with temporal lobe epilepsy (TLE) often suffer from comorbid psychiatric diagnoses such as depression, anxiety, or impaired cognitive performance. Endocannabinoid (eCB) signaling is a key regulator of synaptic neurotransmission and has been implicated in the mechanisms of epilepsy as well as sever...
journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
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journal_title:CNS neuroscience & therapeutics
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journal_title:CNS neuroscience & therapeutics
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journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,meta分析,评审
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journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
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journal_title:CNS neuroscience & therapeutics
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journal_title:CNS neuroscience & therapeutics
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journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:CNS neuroscience & therapeutics
pub_type: 杂志文章,评审
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