台灣山菊化學成分及生物活性之研究

Studies on the Chemical Constituents and Cytotoxicity of Farfugium japonicum (L.) Kitam. var. formosanum (Hayata) Kitam

謝菘斐(Sung-Fei Hsieh)

指導教授 ： 張芳榮

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2004年)

摘要

中文摘要

台灣山菊(Farfugium japonicum (L.) Kitam. var. formosanum (Hayata) Kitam)屬於菊科(Compositae)植物，為台灣特有變種，主要分佈於在海拔約100-2000m。在台灣本植物全草被視為民間用藥(folk medicine)治療風熱感冒；根部用水煎服治療咽喉炎；根部搗爛外敷亦可治療跌打損傷；其新鮮全葉治療疔瘡潰瘍；其葉柄可供食用，主治膀胱炎。由於台灣山菊屬於台灣特有植物，因而選擇台灣山菊，做為研究題材，探討其化學成分與其生物活性作用。
本研究自台灣山菊植物中共分離得到二十九個化合物，包括五個eremophilanes：farformolide B (1)、8??,10??-dihydroxy-6??-methoxy- eremophilenolide (2)、6??,8???z10??-trihydroxyeremophilenoalide (3)、3??-acetoxyl-8??-hydroxy-6??-methoxyeremophil-7(11),9-dien-8,12-olide (4)、8??-hydroxy-6??-methoxyeremophil-7(11),9-dien-8,12-olide (5)；四個furanoereomophilanes：10??-hydroxy-6??-methoxyfuranoeremophilane (6)、furanoeremophilan-6??,10??-diol (7)、6??-ethoxy-10??-hydroxyfurano eremophilane (8)、farfugin A (9)；一個norsesquiterpene：liguhodgsonal (10)；三個diterpenes: phytol (11)、phytan-3-methoxy-1,2-diol (12)、phytan-1,2,3-triol (13)；一個phenolic：petasiphenol (18)；一個 quinol：4-acetonyl-3,5-dimethoxy-p-quinol (14)；六個benzenoids：caffeic acid (15)、methyl caffeate (16)、methyl 4-hydroxy-3-methoxycinnamate (17)、p-hydroxybenzaldehyde (19)、4-hydroxy phenyl methyl ketone (20)、p-hydroxybenzoic acid (21)；五個triterpenes：friedelin (22)、friedelan-3??-ol (23)、ursolic acid (24)、??-amyrin (25)、??-amyrin acetate (26)；二個steroids：??-sitosterol (27) 與stigmasterol (28)混合物 、??-sitosteryl-3-O-??-D-glucoside (29) 與 stigmasteryl-3-O-??-D-glucoside (30) 混合物；一個fatty acid：palmitic acid (31)。
其中化合物3、4與8為新化合物；2、5、7、10、12~24、29與30為第一次自山菊屬植物中分離得到，所有化合物都經由光譜及質譜分析加以證明。
上述化合物在細胞毒殺試驗中，化合物2與8對乳癌細胞(MDA-MB-231)、(MCF 7)、肝癌細胞(Hep G2)、(Hep 3B)具有顯弱的細胞毒殺效果。化合物6、7、16對肺癌細胞(NCH460)具有顯弱的細胞毒殺效果。
在生物活性試驗方面，化合物16、17能刺激嗜中性白血球產生超氧自由基，進而達到抗發炎的效果。

關鍵字

抗發炎 ； 細胞毒殺試驗 ； 倍半帖類 ； 台灣山菊

並列摘要

Abstract

Farfugium japonicum (L.) Kitam. var. formosanum (Hayata) Kitam is the variation of Compositae family. The plant is indigenous to Taiwan and distributes through sea-level about 100-2,000 m. The whole plant can be used as antipyretic and the roots are used to treat pharyngitis. The ground plants are used to cure wound or hurt. Besides, the fresh leaves are also used to treat furuncle and ulcer. Some people would like to eat the petioles which are usefulness for cystitis treatment. Since the plant is indigenous to Taiwan and unique in Compositae family, we chosen the plant as our research topic. We try to discover the active components from the plant of Farfugium japonicum (L.) Kitam. var. formosanum (Hayata) Kitam and investigated their bioactivity.
Twenty-nine compounds isolated in this study belong to nine classes of natural products, which are listed as follows 1) eremophilanes (5)：farformolide B (1), 8??,10??-dihydroxy-6??-methoxyeremophilenolide (2), 6??,8???z10??-trihydroxyeremophilenoalide (3), 3??-acetoxyl-8??-hydroxy- 6??-methoxyeremophil-7(11),9-dien-8,12-olide (4) and 8??-hydroxy-6??- methoxyeremophil-7(11),9-dien-8,12-olide (5); 2) furanoereomophilanes (4)：10??-hydroxy-6??-methoxyfuranoeremophilane (6), furano- eremophilan-6??,10??-diol (7), 6??-ethoxy-10??-hydroxyfurano- eremophilane (8), and farfugin A (9); 3) norsesquiterpene (1)：liguhodgsonal (10); 4) diterpenes (3)：phytol (11), phytan-3-methoxy-1,2- diol (12), phytan-1,2,3-triol (13); 5) phenolic (1)：petasiphenol (18); 6) quinol (1)：4-acetonyl-3,5-dimethoxy-p-quinol (14); 7) benzenoids (6)：caffeic acid (15), methyl caffeate (16), methyl 4-hydroxy-3-methoxy- cinnamate (17), p-hydroxybenzaldehyde (19), 4-hydroxy phenyl methyl ketone (20), and p-hydroxybenzoic acid (21); 8) triterpenes (5)：friedelin (22), friedelan-3??-ol (23), ursolic acid (24), ??-amyrin (25), and ??-amyrin acetate (26); 9) steroids (2)：the mixture of ??-sitosterol (27) and stigmasterol (28), and the mixture of ??-sitosteryl-3-O-??-D-glucoside (29) and stigmasteryl-3-O-??-D-glucoside (30); 10) fatty acid (1)：palmitic acid (31).
The structures of the compounds were elucidated by modern spectral and mass analyses. Among 3, 4 and 8 are new compounds. Compound 2, 5, 7, 10,12~24, 29 and 30 are isolated from the genus Farfugium for the first time.
Compounds 2 and 8 showed unapparent cytotoxicity against MDA-MB-231, MCF 7, Hep G2 and Hep 3B cell lines. Compounds 6, 7 and 16 exhibit cytotoxicity for NCH460 cell line. Furthermore, Compounds 16 and 17 also can achieves anti-inflammation effect by the superoxide free radical which are stimulate by human neutraphils.

並列關鍵字

cytotoxicity ； anti-inflammation ； eremophilane ； furanoeremophilane ； sesquiterpene ； Farfugium japonicum

參考文獻

第七章? 參考文獻

1. 楊遠波，劉和義，彭鏡毅，施炳霖，呂勝由，「台灣維管束植物簡誌」，中華民國行政院農業委員會，2000，p.256-257, 380。

2. Peng, C.-I.; Chang, K.-F.; Li, H.-L. In compositae: Flora of Taiwan Volume 4; Hung, Tseng-Chieng, Ed.; the Editorial Committee of the Flora of Taiwan; the Republic of Taiwan, 1998, 807-1101.

3. 張光雄，邱年永，「原色臺灣藥用植物圖鑑 (1)」，南天書局，1992，p. 219-233。

4. 張光雄，邱年永，「原色臺灣藥用植物圖鑑 (2)」，南天書局，1995，p. 240-256。