Tan Charlene Siew-Hon, Ho Christabel Fung-Yih, Heng Swan-Ser, Wu Jui-Sheng, Tan Benny Kwong-Huat, Ng Yee-Kong, Sun Grace Y, Lin Teng-Nan, Ong Wei-Yi
Department of Anatomy, National University of Singapore, Singapore, 119260, Singapore.
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Neuromolecular Med. 2016 Sep;18(3):441-52. doi: 10.1007/s12017-016-8404-z. Epub 2016 Jun 18.
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.
鳄嘴花（Clinacanthus nutans Lindau），在东南亚通常被称为沙巴蛇草，因其具有止痛、抗病毒和抗炎特性而在民间医学中被广泛使用。我们最近的研究为表观遗传因素对胞质磷脂酶A2（cPLA2）mRNA表达的调控提供了证据（Tan等人，《分子神经生物学》。doi: 10.1007/s12035-015-9314-z，2015年）。这种酶催化花生四烯酸从甘油磷脂中释放出来，并形成促炎性类二十烷酸或有毒的脂质过氧化产物，如4-羟基壬烯醛。在本研究中，我们研究了鳄嘴花乙醇叶提取物对人神经母细胞瘤SH-SY5Y细胞和小鼠原代皮质神经元中cPLA2 mRNA表达的表观遗传调控作用。鳄嘴花可调节组蛋白去乙酰化酶（HDAC）抑制剂MS-275、MC-1568和TSA对SH-SY5Y细胞中cPLA2表达的诱导作用。鳄嘴花提取物还抑制组蛋白乙酰化酶（HAT）活性。在经历0.5小时氧糖剥夺损伤（OGD）的原代皮质神经元中，cPLA2 mRNA表达水平升高。鳄嘴花处理可显著抑制这种升高。用HDAC抑制剂MS-275处理原代神经元可增强OGD诱导的cPLA2 mRNA表达，而鳄嘴花提取物可调节这种升高。Tip60 HAT抑制剂NU9056也可降低OGD刺激的cPLA2 mRNA表达增加。鉴于cPLA2在促炎性类二十烷酸产生和自由基损伤中的关键作用，以及表观遗传对基因的影响通常是持久的这一事实，结果表明鳄嘴花及其植物化学物质可通过对cPLA2表达的表观遗传调控，抑制花生四烯酸衍生的促炎性类二十烷酸的产生和慢性炎症。
