內皮細胞表達細胞黏附因子，以及單核球黏附到內皮細胞上，在動脈粥狀硬化的過程中扮演一個重要的角色。鞣花酸（ellagic acid）是一種廣泛存在於水果及堅果類如覆盆子、草莓、核桃、葡萄中的酚類化合物。先前研究顯示鞣花酸具有抗氧化的特性。因此在本研究中，先以總抗氧化能力試驗（TEAC）、抑制LDL氧化試驗以及清除DPPH自由基的能力，來評估鞣花酸的抗氧化能力。之後，並探討鞣花酸是否可下降細胞內由IL-1β所誘發的自由基的生成，再以同步定量聚合?鏈反應（real-time PCR），來探討鞣花酸對內皮細胞的血管細胞黏附因子（VCAM-1）、細胞間的細胞黏附因子（ICAM-1）及內皮細胞白血球黏附因子（E-selectin）的表現。並探討對於抑制IL-1β所誘發產生的黏附因子的表現是否在轉錄的層次。結果顯示，在體外試驗中，鞣花酸的TEAC 為2.38±0.54，抑制LDL氧化的IC50為18.21±0.49 nmol/L ，清除DPPH自由基的IC50為0.49±0.07 nmol/L。由MTT test得知鞣花酸在50 μＭ濃度以下，不具有細胞的毒殺性。鞣花酸在濃度50 μＭ時可以明顯抑制細胞激素IL-1β所誘發的單核球細胞U-937黏附到內皮細胞上。而在抑制由IL-1β所誘發的細胞內自由基的生成中，證實鞣花酸具有下降細胞內自由基的生成，並呈現劑量相關性。而在黏附因子的表現上，鞣花酸也具有抑制黏附因子VCAM-1和E-selectin mRNA的表現，且在濃度為50 μＭ（p <0.05）效果最佳。而鞣花酸也可以抑制經由IL-1β所誘發的轉錄因子NF-κB p65和p50的活化。因此，鞣花酸可抑制經由IL-1β所誘發的轉錄因子NF-κB p65和p50的活化，並進而抑制VCAM-1的表現，降低單核球的黏附作用。故由結果證實，鞣花酸可能具有抗發炎的特性並在預防動脈粥狀硬化上扮演重要角色。; Expression of cell adhesion molecules by the endothelium and the attachment of monocytes to endothelium may play a major role in atherosclerosis. Ellagic acid is a phenolic compound presents in fruits and nuts including raspberries, strawberries, walnuts and grapes. Previous study indicated that ellagic acid possess antioxidant activity in vitro. In this study, we investigated the antioxidative effects of ellagic acid using the trolox equivalent antioxidant capacity (TEAC) assay、inhibition of LDL oxidation (IC50) and DPPH radicals scavenging ability (IC50). The effects of ellagic acid on the formation of intracellular reactive oxygen species (ROS) and expression of vascular cell adhesion molecule-1 (VCAM-1)、intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule (E-selectin) induced by IL-1β in human umbilical vein endothelial cells (HUVECs) are also investigated. The present study found that the TEAC value of ellagic acid is 2.38±0.54，the inhibition of LDL oxidation (IC50) is 18.21±0.49 nmol/L, and the scavenging ability of DPPH radicals (IC50) is 0.49±0.07 nmol/L. The concentration of ellagic acid up to 50 μＭ was not cytotoxic from MTT test. Ellagic acid significantly reduced the binding of human monocytic cell line, U-937, to IL-1β treated HUVECs.The production of ROS induced by IL-1β was dose-dependently suppressed by ellagic acid. Supplementation with increasing doses of ellagic acid up to 50 μＭ was most effective for the inhibition of the expression of VCAM-1 and E-selectin. Furthermore, the inhibition of IL-1β induced VCAM-1 expression by ellagic acid was manifested on the suppression of nuclear translocation of p65 and p50. In conclusion, ellagic acid inhibits IL-1β induced nuclear translocation of p65 and p50 thereby suppress the expression of VCAM-1, resulting in decrease of monocytes adhesion. Thus ellagic acid has anti-inflammatory properties and may play an important role in the prevention of atherosclerosis.
