石栗葉化學成份及生物活性之研究

Studies on the Chemical Constituents and Bioactivities from Leaves of Aleurites moluccana

許宸泓(Chen-Hung Hsu)

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(2016年)

摘要

石栗(Aleurites moluccana)為一種傳統藥用植物，屬於大戟科(Euphorbiaceae)，用於治療疼痛，發熱，哮喘，肝炎，胃潰瘍和發炎等疾病。在現代藥理研究中，經由動物模式發現石栗葉的含水乙醇萃取物對老鼠具有顯著的抗發炎效果。
在本研究中，以活性導向方式進行石栗枝葉95%乙醇萃取物的分離純化，石栗枝葉之粗萃取物和正己烷層、乙酸乙酯層、正丁醇層和水層，藉超氧陰離子和彈性蛋白酶釋放的試驗來評估其體外抗發炎的活性，其中，乙酸乙酯層與正丁醇層表現出顯著的抗發炎活性。經由一系列管柱層析的純化過程，由乙酸乙酯層得到十六個化合物，包括三個casbane-類型雙萜類，其中兩個新的casbane化合物命名為aleucasbanes A‒B （1‒2）和6,9-dihydroxy-casba-3E,7E,11E-trien-5-one (3), 原名為1,4-dihydroxy-2E,6E,12E-trien-5-one-casbane、十個C13 nor-isoprenoids 4‒13、一個podocarpane化合物aleuritane A （14）和兩個新的ethyl phenylpropanoates 15和16。其中，化合物1‒2和16，經由各種光譜分析確定為新化合物，而15為首次於天然物中發現。另外，三個casbane-類型雙萜類1‒3和兩個新的ethyl phenylpropanoates 15和16進一步進行A-549、HepG2和MDA-MB-231等癌細胞毒殺活性的測試，而十個C13 nor-isoprenoids 4‒13與aleuritane A (14) 進行細胞毒殺與抗纖維化等活性的測試。化合物1‒3、15與16均沒有癌細胞毒殺效果，而6、10、11和14具有抑制纖維母細胞纖維化的潛力。

關鍵字

石栗 ； 抗發炎 ； 抗纖維化

並列摘要

Aleurites moluccana belonging to the Euphorbiaceae family is a traditional medicinal plant used to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammation. In modern clinical studies, the aqueous ethanolic extract of A. moluccana leaves was found to possess anti-inflammatiory effect on rat ear in an animal model.
In the present study, 95% ethanol extract of A. moluccana twigs and leaves were isolated and separated according to bioactive-guided fractionation. The crude extract, n-hexane, ethyl acetate, n-butanol and aqueous layers were evaluated for their anti-inflammatory activity by superoxide anion and elastase release releasation assays. Of which, n-butanol and ethyl acetate layers showed significal anti-inflammatory activity. After separation via a serious column chromatography, 16 compounds were purified form the EtOAc layer, including five casbane-type diterpenoids, two new casbanes (1‒2) and 6,9-dihydroxy-casba-3E,7E,11E-trien-5-one (3), original nane 1,4-dihydroxy-2E,6E,12E-trien-5-one-casbane, ten C13 nor-isoprenoids 4‒13, one podocarpane aleuritane A (14), and two new ethyl phenylpropanoates 15 and 16. Among these isolates, 1–2 and 16 are identified as new compounds by dervise spectroscopic analyses whereas 15 is firstly occurred in nature. Futhermore, three casbane-type diterpenoids 1–3, ethyl phenylpropanoates 15 and 16 were assaed for cytotoxicity against A-549, HepG2, and MDA-MB-231 cancer cells, whereas C13 nor-isoprenoids 4‒13, and aleuritane A (14) were conduced the cytotoxicity and anti-fibrosis testes. 1‒3、15 and 16 showed no cytotoxicity while 6, 10, 11, and 14 demonstrated the inhibitory effects on anti-fibrosis and anti-migration.

並列關鍵字

Aleurites moluccana ； anti-inflammatory ； anti-fibrosis

參考文獻

1. World Health Organization., 2014.

2. Wynn, T. A.；Ramalingam, T. R. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat. Med. 2012, 18, 1028‒1040.

3. Canady, J.；Karrer, S.；Fleck, M. Bosserhoff AK.Bosserhoff, Fibrosing connective tissue disorders of the skin: molecular similarities and distinctions. J Dermatol Sci. 2013, 70, 151‒158.

4. Samuele De, M.；Marco, M.；Stefania, S.；Chiara, R.；Laura, A.；Luciano, T.；Antonio, B.；Gianluca, S. B. Cellular and molecular mechanisms of hepatic fibrogenesis leading to liver cancer. Transl Gastrointest Cancer, 2012, 1, 88‒94.

5. Mendes Hoepers, S.；Tolentino de Souza, H. G.；Meira Quintão, N. L.；Roberto Santin, J.；Cechinel Filho, V.；Silva, R. M.；Garcia Couto, A.；Simão da Silva, K. A. Topical anti-inflammatory activity of semisolid containing standardized Aleurites moluccana L. Willd (Euphorbiaceae) leaves extract. Journal of Ethnopharmacology. 2015, 173, 251‒255.