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Clinacanthus nutans Extracts Modulate Epigenetic Link to Cytosolic Phospholipase A2 Expression in SH-SY5Y Cells and Primary Cortical Neurons

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Abstract

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.

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Acknowledgments

We thank Ms. Annie Hsu from the Department of Pharmacology, NUS, for guidance on preparation of extracts from C. nutans and Ms. Andrea Foo, Jia-Yun Yip, and Victoria E. Buckland from the National Junior College who participated in this work as part of their school research attachment programme.

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Authors and Affiliations

  1. Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore

    Charlene Siew-Hon Tan, Christabel Fung-Yih Ho, Swan-Ser Heng, Yee-Kong Ng & Wei-Yi Ong

  2. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC

    Jui-Sheng Wu & Teng-Nan Lin

  3. Department of Pharmacology, National University of Singapore, Singapore, 119260, Singapore

    Benny Kwong-Huat Tan

  4. Department of Biochemistry, University of Missouri, Columbia, MO, USA

    Grace Y. Sun

  5. Institute of Biomedical Sciences, Academia Sinica, Rm 404, Taipei, 11529, Taiwan, ROC

    Teng-Nan Lin

  6. Neurobiology and Ageing Research Programme, National University of Singapore, Singapore, 119260, Singapore

    Wei-Yi Ong

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  1. Charlene Siew-Hon Tan
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Tan, C.SH., Ho, C.FY., Heng, SS. et al. Clinacanthus nutans Extracts Modulate Epigenetic Link to Cytosolic Phospholipase A2 Expression in SH-SY5Y Cells and Primary Cortical Neurons. Neuromol Med 18, 441–452 (2016). https://doi.org/10.1007/s12017-016-8404-z

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