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The effect of adlay bran extract on the increment of high-density lipoprotein biogenesis

Advisor : 江文章


代謝症候群(metabolic syndrome) 是指合併全身性代謝失調的症狀,並增加罹患糖尿病與心血管疾病的風險。而血中高密度脂蛋白(high-density lipoproteins, HDLs) 濃度與動脈心血管疾病罹患率呈高度負相關,被視為一抗動脈硬化的脂蛋白。ATP-binding cassette transporter A1 (ABCA1) 為細胞膜上的轉運蛋白,可將細胞內磷脂質及游離膽固醇轉運至初生的輔脂蛋白A-I (apolipoprotein A-I, apo A-I) ,參與HDL 的生合成。膽固醇酯轉移蛋白(cholesteryl ester transfer protein, CETP) 負責脂蛋白間膽固醇酯(cholesteryl ester, CE) 及三酸甘油酯(triglyceride, TG) 的交換,而抑制CETP 可促使HDL 透過膽固醇逆向運送(reverse cholesterol transport, RCT) 路徑將膽固醇由動脈壁運回肝臟中代謝。薏苡(Coix lacryma-jobi L. var. ma-yuen Stapf.) 自古以來不僅供作食用,亦為藥膳或食療法中之重要材料,近年來許多研究指出薏仁具有抗發炎、降血糖、降血脂的活性,且具有提升高密度脂蛋白之功效。故本研究旨在利用細胞模式探討薏仁麩皮萃取物提升高密度脂蛋白生合成之可能機制,以及分析薏仁麩皮萃取物活性區分層中可能的有效成分。然而,文獻也曾指出發炎反應會削弱RCT 的作用,因此,本研究將使用鼠巨噬細胞株RAW264.7 篩選具抗發炎活性之萃取物,再進一步分析該樣品提高HDL 的能力。結果顯示,薏仁麩皮水萃物 75%乙醇可溶區分物(ABW-E75) 及薏仁麩皮 80%乙醇萃取物之水區分物(ABE80-Wa) 皆可顯著提高HepG2 之apo A-I 和 ABCA1 mRNA 的表現量,且ABW-E75 可抑制CETP mRNA 的表現。在抗發炎平台的篩選結果中,ABW-E75 則促進RAW264.7 環氧合酶第二型(cyclooxygenase-2, COX-2) 及核轉錄因子-кB (nuclear transcription factor кB, NF-кB) 的基因表現。經HPLC 分析結果得知ABW-E75 中主要的酚類化合物為ferulic acid、caffeic acid 及 protocatechuic acid;以GC 分析脂肪酸組成的結果則以 oleic acid 含量最高,其次為 linoleic acid及 palmitic acid;以GC 分析其中植物固醇的結果顯示β-sitosterol 為ABW-E75 中最主要的植物固醇。本研究結果顯示,薏仁麩皮具有抗動脈硬化的能力,可能是藉由提高肝臟中apo A-I 和ABCA1 的表現以促進HDL 生合成,同時抑制肝臟生成CETP,並透過促進巨噬細胞表現COX-2 蛋白進而形成成熟的HDL。

Parallel abstracts

Metabolic syndrome is a combination of the medical disorders that, when occurs together, increases the risk of developing diabetes and cardiovascular disease. High-density lipoproteins (HDLs) have been shown to be inversely associated with the risk of atherosclerotic cardiovascular disease, thus considered as antiatherogenic lipoproteins. ATP-binding cassette transporter A1 (ABCA1) is a membrane transporter that mediates the efflux of phospholipid and free cholesterol to lipid-poor apolipoprotein A-I (apo A-I), the major protein constituent in HDL particles, that contributes to HDL biogenesis. Cholesteryl ester transfer protein (CETP) transfers of cholesteryl ester (CE) and triglyceride (TG) between non-HDL and HDL. HDL can be raised through CETP inhibition via the reverse cholesterol transport (RCT) pathway, which then moves cholesterol from the artery wall back to the liver for excretion. Adlay (Coix lacryma-jobi L. var. ma-yuen Stapf.) seeds, also called Job’s tears, are one of the components of traditional Chinese medicine and have long been recognized to be beneficial to the human body, and recent studies reported that components in adlay seeds possess anti-inflammatory activity, hypoglycemic and hypolipidemic effects, especially in raising HDL levels. The aim of this study is to elucidate how adlay bran extracts affect high-density lipoprotein biogenesis via cell model, as well as to investigate the active compounds in the active fraction of adlay bran extracts. However, evidence from many recent studies has also indicated that the inflammatory process impairs RCT. For this reason, we use the cell line RAW264.7 to screen for the anti-inflammatory effect of the most active extracts, and then focusing on the HDL- rising properties of these adlay bran extracts. The results showed that both adlay bran water extract- 75% ethanolic soluble fraction (ABW-E75) and water fraction of adlay bran 80% ethanolic extract (ABE80-Wa) increased apo A-I and ABCA1 mRNA expression, while on the other hand, ABW-E75 also decreased CETP mRNA expression in HepG2 cells. In the platform for screening anti-inflammatory materials, ABW-E75 has induction effect on Cyclooxygenase-2 (COX-2) and Nuclear transcription factor kappa B (NF-кB) gene expression in RAW264.7 cells. Based on the HPLC analysis, the more abundant phenolic compounds comprised in ABW-E75 in orders are ferulic acid, caffeic acid and protocatechuic acid; on the other hand, oleic acid, linoleic acid and palmitic acid were the major fatty acids, and β-sitosterol is the major phytosterol in ABW-E75 which was analyzed by GC. Adlay bran may have an anti-atherogenic property by increasing apo A-I and ABCA1 expression, decreasing CETP expression of liver, and also enhancing HDL maturation via COX-2 expression of macrophages.