RGD Reference Report - 4'-O-ß-D-Glucosyl-5-O-Methylvisamminol, A Natural Histone H3 Phosphorylation Epigenetic Suppressor, Exerts a Neuroprotective Effect Through PI3K/Akt Signaling Pathway on Focal Cerebral Ischemia in Rats. - Rat Genome Database
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4'-O-ß-D-Glucosyl-5-O-Methylvisamminol, A Natural Histone H3 Phosphorylation Epigenetic Suppressor, Exerts a Neuroprotective Effect Through PI3K/Akt Signaling Pathway on Focal Cerebral Ischemia in Rats.

Authors: Chang, Chih-Zen  Wu, Shu-Chuan 
Citation: Chang CZ and Wu SC, World Neurosurg. 2016 May;89:474-88. doi: 10.1016/j.wneu.2016.01.061. Epub 2016 Feb 8.
RGD ID: 13782346
Pubmed: (View Article at PubMed) PMID:26868427
DOI: Full-text: DOI:10.1016/j.wneu.2016.01.061


BACKGROUND: A bursting inflammation has been observed that compromises neurologic function in patients who experience stroke. We sought to examine the neuroprotective efficacy of 4'-O-ß-D-glucosyl-5-O-methylvisamminol (OGOMV), a novel histone H3 phosphorylation epigenetic suppressor) in a transient middle cerebral artery occlusion (tMCAO).
METHODS: A rodent tMCAO model was used. Administration with 400 µg/kg/day OGOMV was initiated 12 hours before (prevention) and 1 hour after animals were subjected to tMCAO (reversal). The cerebral cortex was harvested to examine protein kinase B (PI3D/Akt), 5-bromo-2'-deoxyuridine (Western blot), and caspases (reverse-transcription polymerase chain reaction). In addition, cerebrospinal fluid samples were collected to examine interleukin 1-ß, interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α (reverse-transcription polymerase chain reaction).
RESULTS: Cortical 5-bromo-2'-deoxyuridine and phospho-PI3D/Akt were reduced in tMCAO animals, compared with the healthy controls but increased in the OGOMV treatment and prevention groups. Activated cortical caspase-3,-6, and -9a as well as increased IL-1ß and TNF-α levels were observed in the tMCAO animals (P < 0.05). Both prevention and treatment with OGOMV significantly reduced cleaved caspase-3 and -9a groups, but no significant change in caspase-6 was noted. Perifosine, an Akt inhibitor, was added to reduce the bioexpression of phospho-P13D/Akt, and Bcl-2 level and increased cleaved caspase-9a level in both OGOMV prevention and treatment tMCAO groups (P > 0.05).
CONCLUSION: Our study suggests that OGOMV could exert a neuroprotective effect by inhibiting the P13D/Akt protein, attenuating inflammation, and cleaved caspase-3- and -9a-related apoptosis. This study also lends credence to support the notion that the prevention of OGOMV could attenuate proinflammatory cytokine mRNA and late-onset caspases in tMCAO and merits further study.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Casp3  (caspase 3)
Casp6  (caspase 6)
Casp9  (caspase 9)

Genes (Mus musculus)
Casp3  (caspase 3)
Casp9  (caspase 9)

Genes (Homo sapiens)
CASP3  (caspase 3)
CASP6  (caspase 6)
CASP9  (caspase 9)


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