| 摘要: | 高血壓在全球內發病率有上升趨勢，是一個重要的公共健康問題。飲食中攝取酚類化合物的含量與罹患慢性疾病（包括心血管疾病和某些癌症）的風險成反比。然而，在眾多種類的酚類化合物對抗高血壓效益尚未清楚。本研究探討酚類化合物對小鼠血管內皮細胞株 (SVEC) 與血管緊縮素轉換? (ACE) 之抑制性及其降高血壓作用機轉。酚類化合物包括三種黃酮如芹菜素、黃芩素及白楊素，七種黃酮醇如高良薑素、楊梅素、漆黃素、山奈酚、槲皮素、蘆丁及桑色素和四種酚酸如沒食子酸、綠原酸、咖啡酸及阿魏酸。實驗結果顯示，試驗中的酚類化合物，除了沒食子酸和咖啡酸以外沒有細胞毒性。對於一氧化氮 (Nitric oxide, NO) 及前列環素 (Prostacyclin, PGI2) 之誘導性上，屬於黃酮醇的楊梅素、槲皮素、蘆丁及屬於酚酸的綠原酸表現最佳，也能誘發 eNOS 與 COX-2 之表現、對 H2O2 誘發 ROS 並具抑制性。再者，彼等對 ACE 具有顯著抑制性。就楊梅素及綠原酸而言，對 ACE 抑制動力學表現屬於非競爭型 (Noncompetitive)。在類黃酮的結構式上，A 環 C-5 位置中有羥基 (-OH), B 環 C-3' 與 C-4' 位置中有 -OH 或 B 環有更多的 -OH 以及酚酸結構式上 -OH 較多對抗血壓有較正面助益。總之，楊梅素、槲皮素、蘆丁和綠原酸在 SVECs 或抑制 ACE 活性上有較高的抗高血壓活性。
The worldwide prevalence of hypertension continues to increase, the primary prevention of hypertension has become an important global public health initiative. Dietary intake of phenolic compounds is inversely proportional to the risk of chronic diseases (including cardiovascular disease and certain cancers). However, better results in the classification of phenolic compounds are not yet clear. The effects of selected phenolic compounds on the mechanism of antihypertensive activity in mouse vascular endothelia cell line (SVEC) and angiotensin converting enzyme (ACE) activity were investigated. The phenolic compounds include three flavones such as apigenin, baicalein and chrysin, seven flavonols such as galagin, myricetin, fisetin, kaempferol, quercetin, rutin and morin, and four phenolic acids such as gallic acid, chlorogenic acid, caffeic acid and ferulic acid. The results indicate that all the phenolic compounds except gallic acid and caffeic acid show no cytotoxicity to SVECs. Out of these phenolic compounds, myricetin, quercetin, rutin and chlorogenic acid demonstrate significant induction on the levels of NO and PGI2 as well as on eNOS and COX-2 activities. These four phenolic compounds show marked inhibitory effect on ROS generation in H2O2-induced SVECs. In addition, these four phenolic compounds significantly inhibit ACE. Enzyme kinetic analysis reveals that myricetin and chlorogenic acid is all a noncompetitive inhibition of ACE. The presence of hydroxyl groups on C-5 in the A-ring, and on C-3', C-4' in the B-ring of flavonoids, or more hydroxyl group in phenolic acids enhanced antihypertensive activity. In conclusion, myricetin, quercetin, rutin and chlorogenic acid showed better antihypertensive activity in SVEC and ACE inhibition. |
