Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/56784
標題: 甘草中三帖類物質甘草甜素及甘草次酸之體內及體外之抗發炎活性及機轉探討
In vitro and in vivo Anti-inflammatory Effects and Mechanisms of Glycyrrhizic Acid and 18 Beta-glycyrrhetinic Acid in Licorice
作者: 顏國欽
關鍵字: 基礎研究
Triterpenoid
食品科技
三?類
甘草
免疫調節
發炎
糖皮質激素受器
PI3K
licorice
immune-modulating
inflammation
glucocortocoidreceptor
PI3K
摘要: 中草藥中有效成分之研究為近年來熱門之研究標的,如多酚類 (polyphenols) 及類黃酮類 (flavonoids) 物質,在細胞內之生理活性如抗發炎、清除自由基等功能已被廣泛探討。中草藥中另一大類物質為萜類 (terpenoids),在結構上和固醇類 (sterol)物質有極高之相似性。固醇類物質在人體生理內具有相當重要之角色,如糖皮質固醇 (glucocorticoid) 可專一性結合至糖皮質固醇受器 (glucocorticoid receptor) 以抑制細胞中 NF-κB 之活化,可調控發炎反應。但對於三萜類在動物體中是否與固醇類有相似作用機轉進而影響細胞中之發炎相關路徑,此方面之研究依然十分缺乏。在本研究室先前研究中,甘草內含量最高之三萜類物質如甘草甜素 (glycyrrhizicacid) 及甘草次酸 (18β-glycyrrhetinic acid),可活化 PI3K/Akt 路徑達到保護神經細胞免於自由基傷害之效果。鑑於中醫常用甘草治療如痛疽瘡瘍及胃腸道潰瘍等症,而這些病症在現代醫學之觀點通常都與發炎反應相關。本研究旨在釐清具有抗發炎或是免疫調節作用之中草藥如甘草,其影響發炎反應之作用是否經由三萜類成分影響固醇類受器相關路徑或是透過其他路徑進行調控。第一年計畫擬探討甘草甜素及甘草次酸對巨噬細胞 RAW264.7 內糖皮質激素受器蛋白質表現及其 PI3K 表現機制蛋白之影響情形,並測定下游與免疫調控相關之蛋白質之表現量。第二年計畫則深入探討三萜類如甘草甜素及甘草次酸介入後,對免疫細胞內之影響。此部份實驗利用 2-D 電泳探討細胞內蛋白質之變動,並將顯著受到調控之蛋白質點進行質譜鑑定,目的在比較甘草甜素及甘草次酸對細胞內蛋白質表現影響之異同。第三年計畫則以 miRNA 之角度進行探討介入其對動物體內miRNA 表現量影響。本部份將以氣管發炎之動物模式驗證甘草甜素及甘草次酸是否具有在體內環境中具抗發炎功效,並分析組織內 miRNA 之表現量。預期結合先前兩部份之研究,交叉驗證甘草甜素及甘草次酸對細胞及動物體內抗發炎路徑之影響。本研究期望提供甘草中三萜類活性物質甘草甜素及甘草次酸在生理中對於調控發炎相關因子之作用機轉,並闡明中草藥調節發炎反應之可能機制,期為未來保健食品開發應用之參考依據。
The active compounds in Chinese herb like phenols and flavonoids are the popularresearch targets in these years. The anti-inflammatory and antioxidant effects of thesecompounds are intensively studied. Triterpenoids in Chinese herb and sterols in animalboth are synthesized from lipid and their structures are highly similar. Sterols play animportant role in animal body, and a kind of sterols called glucocorticoid can specificallybind to glucocorticoid receptor in cells. It will lead to inhibit the activation of NF-κB,and down-regulate the expression of TNF-α and inflammatory syndrome. However, theinteraction between triterpenoids and glucocorticoid receptor remains unclear. Ourprevious study showed that glycyrrhizic acid and 18β-glycyrrhetinic acid, two majorcompounds in licorice, have ability to protect the neurons against damage by PI3K/Aktactivation. Chinese medicine usually uses licorice to cure various ulcer diseases, whichis considered to be related to inflammatory responds in modern medicine. In this threeyears' project, the underlying mechanism like glucocorticoid pathway or other unknownpathway of triterpenoids in licorice which used for immune-modulating by Chinesemedicine will be investigated. In the first year's plan, we choose glucocorticoidreceptor in RAW264.7 cells as target to evaluate the PI3K activation and TNF-αactivation. In the second year's plan, the proteomic analysis of RAW264.7 treated byglycyrrhizic acid and 18β-glycyrrhetinic acid to be performed by 2-D electrophoresis.We also try to find out the activated protein(s) by bioinformatics system and compare theeffects caused by glycyrrhizic acid and 18β-glycyrrhetinic acid. In the third year's plan,we aim to study the microRNA (miRNA) modulation ability of triterpenoid compounds.In this part, we will integrate the results of previous studies to confirm the miRNAregulating ability of glycyrrhizic acid and 18β-glycyrrhetinic acid. In vitro airwayinflammation will be used in this part of experiment to confirm the anti-inflammatoryeffect of glycyrrhizic acid and 18β-glyrcyrrhetinic acid, and try to reveal the miRNAmodulating ability of these two compounds. The result might also able to show themodulating mechanism of Chinese herb on inflammation. It might helpful to understandthe drug engineering and develop nutraceutical.
URI: http://hdl.handle.net/11455/56784
其他識別: NSC99-2628-B005-003-MY3
文章連結: http://grbsearch.stpi.narl.org.tw/GRB/result.jsp?id=2103579&plan_no=NSC99-2628-B005-003-MY3&plan_year=99&projkey=PD9907-0693&target=plan&highStr=*&check=0&pnchDesc=%E7%94%98%E8%8D%89%E4%B8%AD%E4%B8%89%E5%B8%96%E9%A1%9E%E7%89%A9%E8%B3%AA%E7%94%98%E8%8D%89%E7%94%9C%E7%B4%A0%E5%8F%8A%E7%94%98%E8%8D%89%E6%AC%A1%E9%85%B8%E4%B9%8B%E9%AB%94%E5%85%A7%E5%8F%8A%E9%AB%94%E5%A4%96%E4%B9%8B%E6%8A%97%E7%99%BC%E7%82%8E%E6%B4%BB%E6%80%A7%E5%8F%8A%E6%A9%9F%E8%BD%89%E6%8E%A2%E8%A8%8E
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