title: Clinacanthus nutans Protects Cortical Neurons Against Hypoxia-Induced Toxicity by Downregulating HDAC1/6.
abstract: 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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Roc.|Institute of Biomedical Sciences, Academia Sinica, Rm 404, Taipei, 11529, Taiwan, Roc.
authors.forename: Hsin-Da
authors.initials: HD
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Rm 404, Taipei, 11529, Taiwan, Roc.
authors.forename: Jui-Sheng
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Rm 404, Taipei, 11529, Taiwan, Roc.
authors.forename: Mei-Han
authors.initials: MH
authors.lastname: Kao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Rm 404, Taipei, 11529, Taiwan, Roc.
authors.forename: Jin-Jer
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO, USA.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Ong
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Roc. bmltn@ibms.sinica.edu.tw.|Institute of Biomedical Sciences, Academia Sinica, Rm 404, Taipei, 11529, Taiwan, Roc. bmltn@ibms.sinica.edu.tw.
authors.forename: Teng-Nan
authors.initials: TN
authors.lastname: Lin
mesh_terms: D027901:Acanthaceae / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D029001:Herbal Medicine / Q000592:standards; D056284:Histone Deacetylase 1 / Q000235:genetics*; D000073864:Histone Deacetylase 6 / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D020521:Stroke / Q000628:therapy
chemical_list: C110550:HDAC1 protein, human; C433811:HDAC6 protein, human; D056284:Histone Deacetylase 1; D000073864:Histone Deacetylase 6
keywords: Gene regulation; HDACs; Stroke; Trichostatin/TSA