白樹仔葉部與莖部化學成分之研究

Chemical Constituents of the Leaves and Stems of Gelonium aequoreum

陳建廷(Chien-Ting Chen)

指導教授 ： 張芳榮

共同指導教授 ： 吳永昌(Yang-Chang Wu)

高雄醫學大學/醫學院/醫學研究所/碩士(2012年)

摘要

白樹仔(Gelonium aequoreum)為大戟科(Euphorbiaceae)白樹屬(Gelonium)之植物，主要分佈於亞洲和非洲之熱帶與亞熱帶地區。本屬植物約有25種，但只有白樹仔為台灣原生特有物種。
在過去的研究中，我們從Gelonium aequoreum分離並鑑定出gelomulide K（GK），在乳癌細胞中其作用為 caspase-independent細胞凋亡之誘導劑，並與紫杉醇具有協同效應，同時在正常細胞中也顯示出較低的毒性。此外，MDA-MB-231癌細胞中給予gelomulide K（GK）治療後，可誘導PARP-1高度活化、AIF核轉位和細胞保護自體吞噬，並同時增加ROS產生和GSH含量減少。
在本研究中，Gelonium aequoreum葉部之二氯甲烷的可溶層，利用管柱層析法得到豐富的gelomulide K（GK）以及三萜類化合物，並利用生物活性導引法分離大量三萜類化合物層以及GK層，一共分離出十個化合物分別為，一個lupane-type三萜類：lupeol (1)、一個taraxerane-type三萜類：taraxerol (2)、兩個oleanane-type三萜類：germanicol (3)、??-amyrin (4)、一個urasane-type三萜類：??-amyrin (5)、兩個D:C-friedourasane-type三萜類：bauerenol (6)、multiflorenol (7)、一個新穎三角環三萜類：cyclogeloniane-3??-ol (8)、一個fernane-type三萜類：fernenol (9)、一個ent-abietane type二萜類：gelomulide K (10)，其中cyclogeloniane-3??-ol (8)為新骨架之化合物。
除此之外，也在白樹仔莖部的乙酸乙酯層以及正丁醇層中共分離到二十個化合物，分別為，一個lupane-type三萜類：lupenone (11)、兩個oleanane-type三萜類：olean-18-en-3-one (12)、olean-12-en-3-one (13)、一個urasane-type三萜類：??-amyrenone (14)、兩個D:C-friedourasane-type三萜類：D:C-friedours-7-en-3-one (15)、multiflorenone (16)、一個新穎三角環三萜類：cyclogeloniane-3-one (17)、一個fernane-type三萜類：fernenone (18)，三個苯環類化合物：chrysophanol (19)、halorosellin C (20)、baisubenzene (22)，兩個三酸甘油酯類化合物tetradecanoic acid (23)、13Z-tetradecanoic acid (24)。這些化合物之中cyclogeloniane-3-one (17)與化合物(8)具有相同的骨架，而halorosellin C (20)以及baisubenzene (22)為新化合物。本實驗所得化合物之生物活性試驗正在進行中。

關鍵字

白樹仔 ； 大戟科 ； 三萜類化合物

並列摘要

Gelonium, a genus of shrubs and small trees belonging to the Euphorbiaceae family, is distributed in the tropical and subtropical parts of Asia and Africa. This genus contains about 25 species, but only G. aequoreum is native to Taiwan.
We had previously reported the isolation of gelomulide K from G. aequoreum, which acted as a caspase-independent cell death inducing agent that possesses synergic effect with paclitaxel in breast cancer cells and has low toxicity towards normal cells. Treatment with gelomulide K induced PARP-1 hyperactivation, AIF nuclear translocation, and cytoprotective autophagy, together with increased ROS production and decreased cellular GSH levels in MDA-MB-231 cancer cell line.
In the present study, the dichloromethane-soluble extract of G. aequoreum leaves was chromatographed using silica gel to obtain gelomulide K (GK) and triterpenoids rich fractions. Bioguided fractionation of the triterpenoids-rich and GK-rich fractions yielded ten compounds, including one lupane-type triterpene: lupeol (1), one taraxerane-type triterpene: taraxerol (2), two oleanane-type triterpenes: germanicol (3), and ??-amyrin (4), one urasane-type triterpene: ??-amyrin (5), two D:C-friedourasane-type triterpenes: bauerenol (6), and multiflorenol (7), one novel triterpene: cyclogelonian-3??-ol (8) one fernane-type triterpene: fernenol (9), and one ent-abietane diterpenoid: gelomulide K (10). Among them, cyclogelonian-3??-ol (8) has a new skeleton of triterpenoid with a 13??,18??-cyclopropane function.
The EtOAc and the n-BuOH layers of G. aequoreum stems were also investigated. Chromatographic separation of those layers yielded twenty compounds, including one lupane-type triterpene: lupenone (11), two oleanane-type triterpenes: olean-18-en-3-one (12), and olean-12-en-3-one (13), one urasane-type triterpene: ??-amyrenone (14), two D:C-friedourasane-type triterpenes: D:C-friedours-7-en-3-one (15), and multiflorenone (16), one new triterpene: cyclogelonian-3-one (17), one fernane-type triterpene: fernenone (18), three benzenoid: chrysophanol (19), halorosellin C (20), and baisubenzene (22). Among these isolates, 17 possesses a new chemical skeleton as that of compound 8, and compounds 20 and 22 are new. The biological activities of the isolates are currently under investigation.

並列關鍵字

gelonium aequoreum ； euphorbiaceae ； gelomulide K ； triterpenoid

參考文獻

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