Clinacanthus nutans Extracts Modulate Epigenetic Link to Cytosolic Phospholipase A2 Expression in SH-SY5Y Cells and Primary Cortical Neurons.
Clinacanthus nutans Lindau (C. nutans), commonly known as Sabah Snake Grass in southeast Asia, is widely used in folk medicine due to its analgesic, antiviral, and anti-inflammatory properties. Our recent study provided evidence for the regulation of cytosolic phospholipase A2 (cPLA2) mRNA expression by epigenetic factors (Tan et al. in Mol Neurobiol. doi: 10.1007/s12035-015-9314-z , 2015). This enzyme catalyzes the release of arachidonic acid from glycerophospholipids, and formation of pro-inflammatory eicosanoids or toxic lipid peroxidation products such as 4-hydroxynonenal. In this study, we examined the effects of C. nutans ethanol leaf extracts on epigenetic regulation of cPLA2 mRNA expression in SH-SY5Y human neuroblastoma cells and mouse primary cortical neurons. C. nutans modulated induction of cPLA2 expression in SH-SY5Y cells by histone deacetylase (HDAC) inhibitors, MS-275, MC-1568, and TSA. C. nutans extracts also inhibited histone acetylase (HAT) activity. Levels of cPLA2 mRNA expression were increased in primary cortical neurons subjected to 0.5-h oxygen-glucose deprivation injury (OGD). This increase was significantly inhibited by C. nutans treatment. Treatment of primary neurons with the HDAC inhibitor MS-275 augmented OGD-induced cPLA2 mRNA expression, and this increase was modulated by C. nutans extracts. OGD-stimulated increase in cPLA2 mRNA expression was also reduced by a Tip60 HAT inhibitor, NU9056. In view of a key role of cPLA2 in the production of pro-inflammatory eicosanoids and free radical damage, and the fact that epigenetic effects on genes are often long-lasting, results suggest a role for C. nutans and phytochemicals to inhibit the production of arachidonic acid-derived pro-inflammatory eicosanoids and chronic inflammation, through epigenetic regulation of cPLA2 expression.
Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
Charlene Siew-Hon
CS
Tan
Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
Christabel Fung-Yih
CF
Ho
Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
Swan-Ser
SS
Heng
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Jui-Sheng
JS
Wu
Department of Pharmacology, National University of Singapore, Singapore, 119260, Singapore.
Benny Kwong-Huat
BK
Tan
Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
Yee-Kong
YK
Ng
Department of Biochemistry, University of Missouri, Columbia, MO, USA.
Grace Y
GY
Sun
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.
Teng-Nan
TN
Lin
Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore. wei_yi_ong@nuhs.edu.sg.|Neurobiology and Ageing Research Programme, National University of Singapore, Singapore, 119260, Singapore. wei_yi_ong@nuhs.edu.sg.
Wei-Yi
WY
Ong
D027901:Acanthaceae / Q000737:chemistry*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D009474:Neurons / Q000187:drug effects; D054467:Phospholipases A2 / Q000235:genetics*; D010936:Plant Extracts / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology
D001549:Benzamides; D010936:Plant Extracts; D011725:Pyridines; C118739:entinostat; D054467:Phospholipases A2
Cancer; Chronic inflammation; Cytosolic phospholipase A2 (cPLA2); Epigenetic; Histone; Neuroinflammation