Clinacanthus nutans Protects Cortical Neurons Against Hypoxia-Induced Toxicity by Downregulating HDAC1/6
Many population-based epidemiological studies have unveiled an inverse correlation between intake of herbal plants and incidence of stroke. C . nutans is a traditional herbal medicine widely used for snake bite, viral infection and cancer in Asian countries. However, its role in protecting stroke da...
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Published in | Neuromolecular medicine Vol. 18; no. 3; pp. 274 - 282 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Springer US
01.09.2016
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Many population-based epidemiological studies have unveiled an inverse correlation between intake of herbal plants and incidence of stroke.
C
.
nutans
is a traditional herbal medicine widely used for snake bite, viral infection and cancer in Asian countries. However, its role in protecting stroke damage remains to be studied. Despite of growing evidence to support epigenetic regulation in the pathogenesis and recovery of stroke, a clear understanding of the underlying molecular mechanisms is still lacking. In the present study, primary cortical neurons were subjected to in vitro oxygen–glucose deprivation (OGD)–reoxygenation and hypoxic neuronal death was used to investigate the interaction between
C
.
nutans
and histone deacetylases (HDACs). Using pharmacological agents (HDAC inhibitor/activator), loss-of-function (HDAC siRNA) and gain-of-function (HDAC plasmid) approaches, we demonstrated an early induction of HDAC1/2/3/8 and HDAC6 in neurons after OGD insult.
C
.
nutans
extract selectively inhibited HDAC1 and HDAC6 expression and attenuated neuronal death. Results of reporter analysis further revealed that
C
.
nutans
suppressed HDAC1 and HDAC6 transcription. Besides ameliorating neuronal death,
C
.
nutans
also protected astrocytes and endothelial cells from hypoxic-induced cell death. In summary, results support ability for
C
.
nutans
to suppress post-hypoxic HDACs activation and mitigate against OGD-induced neuronal death. This study further opens a new avenue for the use of herbal medicines to regulate epigenetic control of brain injury. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1535-1084 1559-1174 |
DOI: | 10.1007/s12017-016-8401-2 |