在近代有關於心血管疾病的研究，從流病上顯示肥胖會較易引起動脈粥狀硬化，藉由油脂中低密度脂蛋白的氧化所引發脂質堆積和發炎現象，進而導致血管阻塞。而目前的研究方向較多是針對microRNAs (miRNAs) target對於調控心血管的生成以及疾病。過去我們研究說明了荷葉具有以下作用：改善高脂飲食所引發的動脈粥狀硬化之作用包括荷葉萃取物降低血管平滑肌細胞增生及位移導致動脈粥狀硬化之作用(附件一)、以及荷葉多酚及其主成份Galleic acid抑制小鼠肥胖及脂肪肝作用(附件二及三)等等，因此本計畫工作探討荷葉多酚和其主成分gallic acid 及 rutin如何調控miRNAs對於心血管疾病的影響，其三年計劃架構如附圖(p.39)。第一年計畫探討microRNA在荷葉多酚及其主成份抑制TNF- 誘導血管平滑肌細胞產生增生與位移之角色;第二年探討microRNA在荷葉多酚及其主成份抑制血管內皮細胞傷害及泡沫細胞產生之角色; 第三年探討荷葉多酚減緩高油脂飲食所引發兔子動脈粥狀硬化之作用及microRNA之角色, 從血管內皮、平滑肌細胞及泡沫細胞形成進行荷葉多酚和其有效成分(gallic acid and rutin) 的作用，並以三種血管细胞及動物試驗探討miRNAs在作用機轉的角色。本計劃若能達到預期成果(如附圖 P.48)，將可建立荷葉多酚萃取物及其它phytochemicals targeting miRNAs來調控血管疾病的完整研究模式。
Epidemiological studies indicated that obesity is associated with increased atherosclerosis. The lipid accumulation and inflammation cause atherosclerosis by oxLDL. The connection between obesity and atherosclerosis is particularly strong. It is important to develop specific pharmacological or nutritional agents to reduced obesity and prevent atherosclerosis. The main research about the atherosclerosis so far focuses on microRNAs target. According to the research, nuciferine leaf has the following effects: the nuciferine leaf extracts (NLE) could improve high-fat-diet atherosclerosis including the NLE reduced vascular smooth muscle cell proliferation and migration to cause atherosclerosis (annex 1). Nuciferine leaf polyphenol extracts (NLPE) and the effectived ingredient (gallic acid and rutin) could suppress fat and fatty liver in the mice (annex 2 & 3). In line with these results, the study researching the NLPE is how to regular miRNAs in atherosclerosis, and the three-year-projected is in the p.39. In first year, we focus on (1) effects of NLPE and the active ingredients (gallic acid and rutin) suppress TNF- to induce cardiovascular smooth muscle cell proliferation and migration; In second year, we determined miRNAs with NLPE and active ingredient that it could inhibit the cardiovascular endothelial cell injury and the process for the form cell . In third year, we will study the inhibitory effects of NLE on high-fat-diet rabbit atherosclerosis. We investigate the expression of miRNAs from cardiovascular smooth muscle cell, endothelial cell, and form cell, then determine miRNAs signal pathway in above three kinds of cell and the animal testing. The conclutions of this study (p.48) may demonstrate the influence of NLE、NLPE and the active ingredients on the mechanism of atherosclerosis by phytochemicals targeting miRNAs regulation.
