- 學位論文
燈心草化學成分及生物活性之研究
Studies on the Chemical Constituents and Bioactivities of Juncus effusus
摘要
燈心草(Juncus effusus L.)為燈心草科(Juncaceae)燈心草屬 (Juncus)之植物。燈心草科植物是遍佈全世界的被子植物。這些物種生長於全世界不同氣候的鹽沼或淹沒之惡地。燈心草在傳統用藥上做為鎮靜，抗焦慮，解熱及消腫等功效來使用。其髓質用於治療焦慮或失眠。 本實驗室曾進行一系列常用中草藥的雌激素活性篩選，結果顯示燈心草的乙醇萃取物有顯著的雌激素(erstrogen)活性。在本實驗中配合活性導引法分離活性成分。在進行一系列的管柱純化後得到2個菲類(phenanthrenes) 新化合物，junfusols A−B (1−2)，10個已知菲類化合物[包括 effusol (3)、dehyroeffusol (4)、2,7-dihydroxy-1,8-dimethyl-5-vinyl-9,10-dihydrophenanthrene (5)、juncusol (6)、dehydrojuncusol (7)、2-hydroxy-7-(hydroxymethyl)-1-methyl-5-vinyl-9,10-dihydrophenanthrene (8)、2,7-dihydroxy-1-methyl-5-aldehyde-9,10-dihydrophenanthrene (9)、dehydoreffusal (10)、juncuenin F (11) 與 desvinyljuncusol (12)]，一個已知芘類(pyrene)化合物[1-methylpyrene-2,7-diol (13)]，4個香豆酸酯類(coumarinic acid esters) 化合物以及1個chroman類結構。結構鑑定主要利用質譜及1D和2D NMR (COSY, HMQC, HMBC, NOESY)等光譜數據，分析以及比對文獻上已知化合物的光譜資料而確定。 本實驗將菲類化合物進行雌激素、抗發炎以及細胞毒殺活性篩選。在雌激素活性方面。在100 μg/mL以下，除了化合物 12 無雌激素促進外其餘皆有活性。但化合物 3−7、10 與 12 在100 μg/mL濃度下對MCF7細胞株亦具有細胞毒性。 在抗發炎活性方面，送測之菲類化合物皆有顯著活性。其中以化合物 3、5、6、8 與 9 對以fMLP/CB 刺激 human neutrophil 細胞產生superoxide anion generation [IC50 (μg/mL)：0.31、0.14、0.25、1.38與1.72]及elastase release [IC50 (μg/mL)：0.92、0.73、0.31、4.17、4.34與4.73]皆有顯著抑制活性。化合物 4 與 7 主要會對elastase release 有抑制作用[IC50 (μg/mL)：0.73與1.30]，然而卻對 superoxide anion generation 產生促進作用。在細胞毒殺方面在20 μg/mL濃度皆無顯著活性。
並列摘要
Juncus effusus L. (Family: Juncaceae, genus: Juncus) is a very common angiosperms plant distributed all over the world. These species usually grow in the salty marshes or badly-drained soils under different climatic conditions. J. effusus was used as a sedative, anxiolytic, antipyretic and detumescence. Its medullae were used to cure irritability and insomnia. In the previous study, we tested a series of Tradition Chinese medicine (TCM) at estrogen activity. The ethanolic extract of J. effusus showed significant estrogenic effect. We investigated on its estrogenic effect followed by bioguided isolation processes. The phytochemical study led to the isolation of two new phenanthrenes compounds, junfusol A-B (1−2), together with 10 known phenanthrenes [including effusol (3), dehyroeffusol (4), 2,7-dihydroxy-1,8-dimethyl-5-vinyl-9,10-dihydro- phenanthrene (5), juncusol (6), dehydrojuncusol (7), 2-hydroxy-7- (hydroxymethyl)-1-methyl-5-vinyl-9,10-dihydrophenanthrene (8), 2,7- dihydroxy-1-methyl-5-aldehyde-9,10-dihydrophenanthrene (9), dehydro- effusal (10), juncuenin F (11), and desvinyljuncusol (12)], 1 pyrene [1-methylpyrene-2,7-diol (13)], 4 coumarinic acid esters, and 1 chroman compound. The structures were elucidated through interpretation of mass and spectroscopic methods, especially 2D NMR techniques (COSY, HMQC, HMBC, and ROESY), and the spectral data of known compounds were compared with those of literature. The phenanthrenes were screened for their estrogenic, anti-inflammatory and cytotoxic activities. The phenanthrenes compounds showed significant estrogen receptor agonist effect except for 12 in a concentration of 100 μg/mL. However, compounds 3−7, 10 and 12 exhibted various cytotoxic effect to a MCF7 cell line in high concentrations > 100 μg/mL. In the anti-inflammatory assay, the phenanthrenes 3, 5, 6, 8 and 9 showed significant anti-inflammatory effect toward superoxide anion generation [IC50 (μg/mL): 0.31、0.14、0.25、1.38 and 1.72] and elastase release induced [IC50 (μg/mL): 0.92、0.73、0.31、4.17、4.34 and 4.73] by fMLP/CB-induced human neutrophils. Compounds 4 and 7 showed effect in inhibiting elastase release [IC50 (μg/mL): 0.73 and 1.30]; however, they promoted superoxide anion generation in the assay system. Moreover, the tested compounds did not show cytotoxicity at 20 μg/mL.