行政院國家科學委員會補助專題研究計畫
行政院國家科學委員會補助專題研究計畫
行政院國家科學委員會補助專題研究計畫
行政院國家科學委員會補助專題研究計畫成果
成果
成果
成果報告
報告
報告
報告
※※※※※※※※※※※※※※※※※※※※※※※※※
※ 六種本土植物及三種中藥活性成分之研究 ※
※ (Chemical and Biological Studies of the Six ※
※ Native Plants and Three Chinese Herbs) ※
※※※※※※※※※※※※※※※※※※※※※※※※※
計畫類別：■個別型計畫 □整合型計畫
計畫編號：NSC －96－2113－M－039－001
執行期間：96 年 8 月 1 日至 97 年 7 月 31 日
計畫主持人：郭悅雄
共同主持人：
計畫參與人員：邱錫臨
成果報告類型(依經費核定清單規定繳交)：■精簡報告 □完整報告
本成果報告包括以下應繳交之附件：
□
赴國外出差或研習心得報告一份
□赴大陸地區出差或研習心得報告一份
■
出席國際學術會議心得報告及發表之論文各一份
□國際合作研究計畫國外研究報告書一份
執行單位：中國醫藥大學中國藥物研究所
中 華 民 國 97 年 9 月 22 日
行政院國家科學委員會專題研究計畫成果報
行政院國家科學委員會專題研究計畫成果報
行政院國家科學委員會專題研究計畫成果報
行政院國家科學委員會專題研究計畫成果報告
告
告
告
六種本土植物及三種中藥活性成分之研究
Chemical and Biological Studies of the Six
Native Plants and Three Chinese Herbs
計畫編號：NSC 96-2113-M-039-001
執行期限：96 年 8 月 1 日至 97 年 7 月 31 日
主持人：郭悅雄 中國醫藥大學中國藥物研究所
計畫參與人員：邱錫臨
一 一 一 一、、、、中文摘要中文摘要中文摘要中文摘要 台灣扁柏是最好的建材，由其材部分 離出二種新骨架化合物，其一且有抗癌活 性。水丁香是民間用藥，用於腎臟炎、水 腫及高血壓，由其全草分出二種新的三萜 化合物。由治療風濕症之黃心柿莖中找出 二種新的萘醌化合物。福杉被用為治療哮 喘、解熱及關節炎，由其心材有二種新的 木酚素化合物被發現。山藥含女性賀爾蒙 之代用品，其中發現二種新化合物及三種 已知化合物，被確認可活化女性荷爾蒙之 α 及 β 型。由可治療腹瀉及抗瘧疾之羅氏鹽 膚木之根找出六種新化合物，其中三種化 合物可以抗煙草之馬賽克病毒。台灣杉可 以抗腐蝕黴為有價值建材，由其根分七種 倍半萜化合物，其中六種為新化合物，另 外亦有找出九種木酚素，其中有六種被確 認為新化合物。 關鍵詞 關鍵詞 關鍵詞 關鍵詞：台灣扁柏；水丁香; 黃心柿；福 杉;山藥；羅氏鹽膚木；台灣杉；細胞毒； 病毒；植物女性荷爾蒙。 Abstract
Chamaecyparis obtusa var. formosana is an important building material, two novel skeleton compounds were isolated from its heartwood. One of two components exhibited strong cytotoxic activity.
Ludwigia octovalvis was used for the treatment of oedema, nephritis, and hypertension. And two new oleanane type derivatives were isolated and elucidated from the its whole plant. Two new naphthoquines were elucidated from the stem of Diospyros maritima, which has been used in a folk medicine as traditional treatments for rheumatic disease. Cunninghamia
lanceolata, a large evergreen tree, is culitivated at low altitude. It has long been used for treatment of asthma, as an analgesic, and of arthritis. Two new lignans were
purified from its heartwood. Yams (Dioscorea alata) have been implicated in the promotion of the health of postmenopausal women. The active components were isolated and purified by HPLC. Five compounds exhibited to activate ERα and β. The root of Rhus
javanica var. roxburghiana were traditionally used in Taiwan as a fold herbal remedy for diarrhea, spermatorrhea, and malaria. In preliminary test, its methanolic extraction showed anti-tobaco mosaic virus. Under the activity-guide, we have discovered three new lignans glycosides possessing this activity, and also purified eight new compounds. Taiwania
cryptomerioides , an important building material with high value in Taiwan. Its heartwood contains more than 6% of essential oil, and many interesting and different skeleton compounds have been reported. In order to survey the secondary metabolism compounds, we have found six new cadinane derivalives together with five new lignans.
Keywords: Chamaecyparis obtusa var.
formosana; Ludwigia octovalvis; Diospyros maritima;
Cunninghamia lanceolata; Dioscorea alata; Rhus javanica var. roxburghiana ; Taiwania cryptomerioides; Cytoxicity; Anti-Tobaco-Mosaic Virus; Phytoestrogen 二 二 二 二、、、、Purpose of Project
In this study, we try to find the biological components and search different compounds in order to understand the plants biosynthesis. The trunk of Chamaecyparis obtusa var. formosana is an important building material in Taiwan due to its decay-resistant characteristic. We have previously investigated many components of heartwood of this plant, and various monoterpenes, sesquiterpenenes, diterpenes,
and lignans. We also discovery many noble skeleton compounds. The purpose of this study continued the compound’s separation, and try to discover the noble skeletonal compounds. The crude extract of Ludwigia octovalvis has been reported possessing antidiabetic and immunosuppressive activity. In our previous reports that showed three new triterpene derivatives inhibiting significant cytotoxicity against KB and HT29 with IC50 in the rang of 1.2-3.6µM. The
genus Diospyros maritima exhibited cytotoxic, ichthyotoxic, germination inhibitory and antimicrobial activities. We try to find the biological active components and continued this chemical study. Cunninghamia lanceolata has long been used as a falk medicine. In order to study the biological isolate, the chemical study was studied in this time. Yams(Dioscorea alata) have been implicated in the promotion of the health of postmenopausal women. The crude extract of Dioscorea alata exhibited to activate ERα and β. The root of Rhus javanica var. roxburghiana are used in Taiwan as a folk herbal remedy for diarrhea, spermatorrhea, and malaria. The preliminary test, its methanolic extraction showed anti-tobaco mosaic virus. Under the activity guide, we have discovered the biological active compounds. Many components were isolated from the Taiwania cryptomerioides possessing many biological activities such as anti-wood decay fungi, cytotoxity, and anti-white ant. Therefore, the chemical investigation was continued.
三 三 三
三、、、、Content of Project
The separative procedure of every plant was achieved as following
plant
methanol methanol extract
partitioned with H2O / EtOAc
EtOAc soluble fraction H2O
Two novel skeleton compounds, 1 and 2 were isolated from the heartwood of C. obtusa var. formosana. The structure 1 was elucidated as a dimeric of monoterpene and norlignan , and structure 2 was elucidated as a norlignan. Compound 1 exhibits potent cytotoxic active against several human cancer cells with IC50 values ranging from
0.19 to 0.52µM. Two new oleanane-type triterpenes, 3 and 4, together with two know compounds, β-amyrin acetate and β-amyrin palmitate, have been isolated from the whole plant of L. octovalvis. We have purified from the stems of D. maritima and discovered two new napnthoquinones, 5 and 6, together with two knowns, 6-hydroxy-5-methoxy-2-methyl -1,4-napnthoquinon and bisisodiospyrin.
From the root of T. cryptomerioides, six new lignans, 7, 8, 9, 10, 11 and 12 were isolated and elucidated. The roots of Rhus javanica var. roxburghiana do folk herb for treating diarrhea, spermatorrhea and malaria. The methanalic extract of the roots of this plant was divided into three fractions, EtOAc soluble, n-BuOH soluble and water soluble fractions. Three new triterpene together with thirty-seven know were reported in the previous reports. In this time, the continuous studies on the n-BuOH fraction was achieved. Three new cyclolignans, 13, 14 and 15, four new lariciresinol-base lignan glycosides, 16,
17, 18 and 19. Four new diepoxylignan
glycoside, 20, 21, 22 and 23, together with eight known compounds were purified from n-BuOH soluble fraction. Meanwhile compounds 21-23 showed moderate inhibition of multiplication of the tobacco mosaic virus. The continuous studies on the roots of Taiwania cryptomerioides, six new cadinane-type sesquiterpenes, 24, 25, 26, 27,
28 and 29 were isolated. The structure of the
new constituents were essentially elucidated by spectral evidence. Two new compounds, hydro-Q9 chromene (30), and γ-tocopherol-9
(31), together with three know compounds were identified and shown to activate human ERα and β. These result provide basic evidence for the beneficial effect of yam for menopausal women. Two new lignans, lanceoline (32) and 5-methoxytrachelogenin (33), together with 5-methoxywikstromal were isolated from the low polar layer of
extract of C. lanceolata.
四、、、、Published papers
1. Chien, S. C., J. Y. Chang, C. C. Kuo, C. C. Hsieh, N. S. Yang, and Y. H. Kuo,* 2007. Cytotoxic and novel skeleton compounds from the heartwood of Chamaecyparis obtusa var. formosana , Tetrahedron Lett., 48, 1567-1569. 2. Chang, C. I. and Y. H. Kuo,* 2007.
Oleanane-type Triterpenes from
Ludwigia octovalvis, J. Asian Nat. Prod. Res., 9(1), 67-72.
3. Chang, C. I. and Y. H. Kuo,* 2007. Two New Naphthoquinones from the Stem of Diospyros maritime, J. Asian Nat. Prod. Res., 9(2), 153-158.
4. Chyu, C. F. and Y. H. Kuo,*2007. New Lignans from the Roots of Taiwania cryptomerioides Hayata. Helv. Chim. Acta., 90(4), 738-747.
5. Ouyang, M. A., Y. S. Wein, R. K. Su, and Y. H. Kuo,* 2007. Rhusemialins A-C, New Cyclolignan Esters from the Roots of Rhus javanica var.
roxburghiana, Chem. Pharm. Bull.,
55(5),804-807.
6. Ouyang, M. A., Y. S. Wein, and Y. H. Kuo,* 2007. Four New
Lariciresinol-based Lignan Glycosides from the Roots of Rhus javanica var. roxburghiana, Helv. Chim. Acta., 90(6), 1099-1105.
7. Ouyang, M. A., Y. S. Wein, Z. K. Zhang, and Y. H. Kuo,* 2007. Inhibitory
Activity against Tobacco Mosaic Virus (TMV) Replication of Pinoresinol and Syringaresinol Lignans and their glycosides from the Roots of Rhus javanica var. roxburghiana, J. Agric Food Chem., 55, 6460-6465.
8. Chyu, C. F., M. R. Ke, Y. S. Chang, S. C. Chien, and Y. H. Kuo,* 2007. New Cadinane-Type Sesquiterpenes from the Roots of Taiwana cryptomerioides Hayata, Helv. Chim. Acta., 90, 1514-1521.
9. Cheng, W. Y., Y. H. Kuo,* and C. J. Huang, 2007. Isolation and
Identification of Novel Estrogenic Compounds in Yam Tuber ( Dioscorea
alata cv. Tainung No 2 ) J. Agric Food Chem., 55, 7350-7358
10. Chao, W. W., Y. H. Kuo and B. F. Lin, 2008. Construction of Promotors Based Immunity Screening System and its Application on the study of Traditional Chinese Medicine Herbs Taiwanese, J. Agric. Chem. and Food Science., 45, 193-205.
OH OH OH O O 1 HO O OH OH 2 HO CH2OR COOH 3 4 R = O OH OMe OH OMe O R = OH 5 R1= OEt, R2= H 6 R1= H, R2= OEt O O H3C R2 R1 O OH HO H3C O R1 R2 OR4 OR3 O R5 H H O 7 R1+ R2 = OCH2 , R3 = R4 = R5 = H 8 R1= H, R2 = R5 = OH, R3 + R4 = CH2 9 R1= R5 = H, R2 = OH, R3 = R4 = CH3 12 O O OCH3 OCH3 OCH3 OH OH H3CO HO OCH3 H3CO OH OCH3 O O C OH OH 13 R2O R1O O O R3 O O 10 R1+ R2 = CH2 , R3 = OH 11 R1= R3 = H, R2 = CH3 14 OH OCH3 C O O OR2 OH OH O OH OH H3CO OH OCH3 H3CO OCH3 R1O R1= R2 = H 15 OH C O R1= R2 = OCH3 O OR2 OH OH R1O H3CO O O OCH3 OH OH 16 OH OCH3 C O R1= R2 = H 17 C OH O R1= R2 = OCH3
O OR2 OH OH R1O H3CO O O OCH3 OR3 OH H3CO OCH3 18 OH OCH3 C O R1= R2 = R3 = H 19 C OH O R1= R2 = R3 = OCH3 OCH3 OCH3 OCH3 HO OH O OR3 OH OR4 R2O O O O H H OCH3 OH R1 H3CO R1 20 OH OCH3 C O R1= R3 = R4 = H, R2 = 21 OH OCH3 C O R1 = R4 = H, R2 = R3 = 22 OH OCH3 C O R1 = R3 = H, R2 = R4 = 23 OH OCH3 C O R1 = OCH3, R2 = R3 = OH O H H 24 O OH 25 O 26 27 HO HO OH HO OH 28 OH 29 HO OH O O HO H3CO OCH3 7 30 O HO 7 31 H3CO HO OH O OH OCH3 H H 32 H3CO HO O OH OCH3 OH H 33 O OCH3
