2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38670Cerebrovascular and heart diseases are the second and third causes of death in Taiwan. Oxidized low-density lipoprotein (oxLDL) is a known major risk factor for accelerating atherogenesis. It involves several critical steps in atherosclerosis including the expression of adhesion molecules on endothelial cells, the production of various pro-inflammatory cytokines and growth factors, the proliferationand migration of vascular cells and the retardation of endothelial regeneration. The early stages of the atherosclerotic process are initiated by accumulation of oxLDL and activation of endothelial cells with subsequent expression of adhesion molecules and increased binding of monocytes to the vascular endothelium. In our preliminary study, we determined the effect of the extracts of Mallotus repandus (MRE), Euphorbia lathyris L. (ELE) and Koelreuteria formosanas (KFE) on inhibitory of LDL oxidation and ApoB fragmentation. Moreover, Mallotus repandus and Capparis spinosa extracts showed great protection on oxLDL-induced cytotoxicity in endothelial cell. Therefore, this three years grant proposal aims to study whether treatment of MRE, ELE and KFE would protect against cardiovascular disease. Therefore, in the first year study, we will focus on studying whether these extracts could inhibit LDL oxidation, rescue human umbilical vein endothelial cells (HUVECs) and macrophage from oxLDL-mediated dysfunction and apoptosis, and inhibit cytokine-induced smooth muscle cell migration and proliferation. In the second year of this study, we will aim to explore the underlying mechanism involved in the preventive effects of herb extracts against oxLDL-indeced apoptosis in endothelial cell and macrophage and the inhibitive of these extracts on cytokine-induced smooth muscle cell migration and proliferation. In the third year of this study, we will propose to isolate and identify the active component of MRE, ELE and KFE. Finally, analyze the anti-atherosclerotic effect of these herb extracts via an animal model.腦血管與心臟疾病在近幾年來則是分居台灣地區十大死因之第二及第三名,僅次 於惡性腫瘤之後。動脈粥狀硬化(atherogenesis)引發的病理機制非常複雜,其形成的成 因主要成因有:氧化型低密度脂蛋白(oxLDL)經由產生自由基而刺激細胞内訊息傳遞 分子造成(1.)血管内皮功能失調;(2.)皮滑肌細胞之增生與位移;(3.)並造成内皮細胞表面 表現異常的黏著分子’例如:ICAM-1 > VCAM-1 ’增加與單核球間之黏著作用;(4.)發炎 反應;(5)以致最終導致内皮細胞與macrophage的傷害甚至凋亡。由此可知心血管疾病 的預防與治療,是一個急待解決與重視的課題。在我們的初步試驗結果中,發現扛香 藤、續隨子與台灣欒木之50%酒精萃取物具有防止ApoB片段化及LDL氧化的效果。 並且證實扛香藤與台灣欒木能顯著保護内皮細胞不受oxLDL之傷害。因此,本研究將 分三年來完成,第一年探討扛香藤、續隨子與台灣欒木之萃取物抗氧化之效果。利用 體外培養人類臍帶靜脈内皮細胞(HUVECs)、平滑肌細胞與巨噬細胞株’以氧化型低密 度脂蛋白(oxLDL)誘導血管内皮細胞與巨嗜細胞之細胞凋亡及巨嗜細胞所誘導之發炎 反應,用來模擬人體内粥狀動脈硬化的形成,第二年深入探討扛香藤、續隨子與台灣 欒木這些天然萃取物作用在血管内皮細胞、皮滑肌細胞與巨噬細胞之保護作用,並釐 清其訊息傳遞路徑與作用機轉’同時研究在oxLDL刺激下’扛香藤、續隨子與台灣欒 木對於内皮細胞與單核球細胞的黏著作用之影響。第三年並利用餵食高膽固醇之動物 模式(紐西蘭大白兔與倉鼠),進一步研究其在活體内保護粥狀動脈硬化之功效。並且針 對具有保護效果之天然萃取物以LC/MS進行有效成分的分離純化及鑑定。氧化型低密度脂蛋白動脈粥狀硬化人類靜脈血管内皮細胞巨噬細胞oxLDLatherogenesisHUVECsmacrophage扛香藤、續隨子與台灣欒木萃取物抑制LDL氧化及保護心血管疾病之功能與機制探討Project