Bakkenolide-IIIa Protects Against Cerebral Damage Via Inhibiting NF-κB Activation.

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 Ther

authors

Jiang Q,Li RP,Tang Y,Wang YQ,Liu C,Guo ML

doi

10.1111/cns.12470

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

943-52

issue

12

eissn

1755-5930

issn

1755-5949

journal_volume

21

pub_type

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