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Bakkenolide-IIIa Protects Against Cerebral Damage Via Inhibiting NF-?B 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, IKK?, I?B? were measured using Western blot. The nuclear translocation and activation of NF-?B 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, IKK?, I?B?, and p65 in cultured hippocampal neurons exposed to OGD. Bakkenolide-IIIa not only inhibited the nuclear translocation of NF-?B in cultured neurons exposed to OGD, but also inhibited the activation of NF-?B 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-?B signaling.

SUBMITTER: Jiang Q

PROVIDER: S-EPMC6493129 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Jiang Qian Q Li Run-Ping RP Tang Ying Y Wang Ye-Qing YQ Liu Chong C Guo Mei-Li ML

CNS neuroscience & therapeutics 20151028 12

<h4>Aims</h4>This study was designed to examine the neuroprotective effects of bakkenolide-IIIa, a major novel compound extracted from the rhizome of P. trichinous.<h4>Methods</h4>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 acti ...[more]

PMID: 26511680

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

Publications

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

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