ReferenceID 87

BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin

J Neurosci

We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dun

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Reference Id
87
Evidence Id
16677
Core Evidence Id
16677
Source Reference Id
147
Herb2 Reference Id
HBREF000320
Subject Paper Key
HBIN037934_24431454
Pubmed Id
24431454
Doi
10.1523/JNEUROSCI.2700-13.2014
Paper Title
BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin
Paper Abstract
We have previously shown that the botanical drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, provides neuroprotection in both in vitro and in vivo brain slice-based models for focal ischemia (Dunn et al., 2011). Intriguingly, plasma levels of the neurotrophin BDNF were increased in patients treated with PBI-05204 in a phase I clinical trial (Bidyasar et al., 2009). We thus tested the hypothesis that neuroprotection provided by PBI-05204 to rat brain slices damaged by oxygen-glucose deprivation (OGD) is mediated by BDNF. We found, in fact, that exogenous BDNF protein itself is sufficient to protect brain slices against OGD, whereas downstream activation of TrkB receptors for BDNF is necessary for neuroprotection provided by PBI-05204, using three independent methods. Finally, we provide evidence that oleandrin, the principal cardiac glycoside component of PBI-05204, can quantitatively account for regulation of BDNF at both the protein and transcriptional levels. Together, these findings support further investigation of cardiac glycosides in providing neuroprotection in the context of ischemic stroke.
Journal
J Neurosci
Publish Year
2014
Experiment Subject
rat
Experiment Type
Animal Experiment
Phenotype Related
Ischemic Stroke
Paper Title Cn
Paper Title En
BDNF mediates neuroprotection against oxygen-glucose deprivation by the cardiac glycoside oleandrin
Bilingual Status
semi_complete