黃連素 (berberine) 是黃連 (小檗鹼植物) 中主要的天然化合物，目前已知具有抗發炎 (anti-inflammation) 和抗腫瘤 (anti-tumor) 等生物活性，然而對於黃連素是否會抑制粥狀動脈硬化形成及其詳細的作用機制到目前為止並不清楚。在本篇論文中，我們首次證實黃連素具有抑制 LDL 氧化及降低氧化型低密度脂蛋白對人類血管內皮細胞 (HUVECs) 所造成的傷害。針對抑制 LDL 氧化實驗中，利用 relative electrophoretic mobility (REM) shift assays、electrophoresis of ApoB fragmentation、lipid peroxidation assay (malondialdehyde production)，證實黃連素可有效抑制硫酸銅所誘導LDL 的氧化。在氧化型低密度脂蛋白對人類血管內皮細胞所造成的傷害實驗中，黃連素抑制氧化型低密度脂蛋白誘發人類臍靜脈內皮細胞的損傷，主要是透過抑制破壞粒腺體導致粒腺體膜電位 (mitochondrial membrane potential)改變，進而抑制細胞凋亡過程中所釋放出的 cytochrome C 和下游基因 caspase 3 之活化，此外，黃連素同時也可降低氧化型低密度脂蛋白誘發人類臍靜脈內皮細胞的細胞內導致 ROS 的產生。綜合以上結果，黃連素或許可應用於臨床上保護氧化型低密度脂蛋白所造成內皮細胞的功能失調及傷害。
The oxidative modification of low-density lipoprotein (oxLDL) is thought to have a central role in the pathogenesis of atherogenesis. Berberine, a natural constituent of plants of the genera Coptis and Berberis, has several anti-inflammation and anticancer biological effects. However, its protective effects on LDL oxidation and endothelial injury induced by oxLDL remain unclear. In this study, we evaluated the antioxidative activity of berberine and how berberine rescues human umbilical vein endothelial cells (HUVECs) from oxidized LDL (oxLDL)-mediated dysfunction. The chemopreventive activity of berberine was defined by the relative electrophoretic mobility (REM) of oxLDL, fragmentation of ApoB, and malondialdehyde production via the Cu++-mediated oxidation of LDL. Berberine also inhibited the generation of ROS and the subsequent mitochondrial membrane potential collapse, chromosome condensation, cytochrome C release, and caspase 3 activation induced by oxLDL in HUVECs. Our results suggest that berberine may protect LDL oxidation and prevent oxLDL-induced cellular dysfunction.
