台灣檫樹根部及莖部化學成分與生物活性研究

Chemical constituents and their bioactivities from the root and stem of Sassafras randaiense

侯雅羚(Ya-Ling Hou)

指導教授 ： 陳益昇

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00002

摘要

台灣檫樹 (Sassafras randaiense (Hayata) Rehder)為台灣固有種，屬於樟科(Lauraceae)檫樹屬 (Sassafras)的中型落葉性喬木，分佈於嘉義以北900~2,400 公尺之闊葉林中。針對近1,400種台灣產之植物進行活性篩選，發現台灣檫樹根部及莖部具有抗結核、抗氧化及抗發炎活性，然而台灣檫樹根部及莖部過去少有徹底地天然物分離研究及其相關活性之研究，只有六個化合物從根部被分離；因此，本研究之目的為針對台灣檫樹根部及莖部進行化學成分及生物活性之探討。
利用活性導向試驗，從台灣檫樹根部乙酸乙酯層萃取物分離得到1個新dimeric neolignan化合物：(+)-sassarandailin (67)，1個天然首次分離flavonoid化合物：(R)-(+)-5,7,3',5'-tetrahydroxyflavanone (77)，以及15個已知化合物：magnolol (52)、β-sitosterol (48)、stigmasterol (68)、trans-docosanylferulate (69)、magnaldehyde D (70)、(2R,3R)-(–)-3-hydroxy-5,7-dimethoxy-3',4'-methylenedioxyflavan (71)、neolitacumone C (72)、(–)-5,3'-di-O-methylepicatechin (73)、(–)-taxifolin (74)、(±)-syringaresinol (75)、magnolignan A (76)、quercetin (78)、(+)-catechin (79)、(+)-9,9'-di-O-trans-feruloyl-5,5'-dimethoxysecoisolariciresinol (80)、(7R,8R,8'R)-(+)-
lyoniresinol (81)。從台灣檫樹莖部乙酸乙酯層萃取物分離得到1個新neolignan化合物：(R)-(–)-sassarandainol (52)，以及10個已知化合物：48、52、68、γ-tocopherol (83)、β-sitosterone (84)、subamolide B (85)、(+)-2β-methoxyclovan-9α-ol (86)、palmitic acid (87)、erythro-7'-hydroxy strebluslignanol (88)、threo-7'-hydroxy strebluslignanol (89)。以上化合物之結構皆以光譜分析決定。
活性實驗中，主量的化合物52對標準菌種 (Mycobacterium tuberculosis H37Rv)顯示具有體外抗結核菌活性，其MIC值為45.0 μg/mL。在抗氧化活性方面，化合物67、75、79、81其ABTS radical scavenging之SC50值分別為28.9、14.0、13.9、19.9 µM，化合物75、79、81其DPPH radical scavenging之SC50值分別為19.2、15.3、28.7 µM。在抗發炎活性方面，化合物80、83、84、85其Emax值分別為77.4、69.5、83.0、71.3 %，可有效抑制NO的生長。

關鍵字

台灣檫樹 ； 樟科 ； 根部 ； 莖部 ； 抗結核病 ； 抗氧化 ； 抗發炎

並列摘要

Sassafras randaiense (Hay.) Rehd. (Lauraceae) is a medium-sized deciduous tree endemic to Taiwan and grows in broad-leaved forests from 900 to 2,400 m through the Island. Approximately over 1,400 species of Formosan plants have been screened for biological activities. The methanolic extract of the root and stem of this plant showed potent anti-tubercular, anti-oxidant, and anti-inflammatory activities. The chemistry and biological activities of Taiwan sassafras was not extensively studied, and only six compounds were isolated from root part. The aims of this study were the isolation of chemical constituents from the root and the stem, and the evaluation of their biological activities.
Firstly, bioassay-guided fractionation of active EtOAc layer from the root of this species led to the isolation of 17 compounds, including one new dimeric neolignan: (+)-sassarandailin (67), one first isolated from nature: (R)-(+)-5,7,3',5'-
tetrahydroxyflavanone (77), along with 15 known compounds including magnolol (52), β-sitosterol (48), stigmasterol (68), trans-docosanylferulate (69), magnaldehyde D (70), (2R,3R)-(–)-3-hydroxy-5,7-dimethoxy-3',4'-methylenedioxyflavan (71), neolitacumone C (72), (–)-5,3'-di-O-methylepicatechin (73), (–)-taxifolin (74), (±)-
syringaresinol (75), magnolignan A (76), quercetin (78), (+)-catechin (79), (+)-9,9'-di-O-trans-feruloyl-5,5'-dimethoxysecoisolariciresinol (80), (7R,8R,8'R)-(+)-
lyoniresinol (81). Second, from the stem of this species led to the isolation of 11 compounds, including one new neolignan: (R)-(–)-sassarandainol (82), along with 10 known compounds including 48, 52, 68, γ-tocopherol (83), β-sitosterone (84), subamolide B (85), (+)-2β-methoxyclovan-9α-ol (86), palmitic acid (87), erythro-7'-
hydroxy strebluslignanol (88), and threo-7'-hydroxy strebluslignanol (89). The structures of these isolates were elucidated by spectral analysis.
Among the isolates, the major compound 52 exhibited anti-tubercular activity against Mycobacterium tuberculosis H37Rv in vitro with the MIC value of 45.0 μg/mL. Compounds 67, 75, 79, and 81 exhibited anti-oxidant activity with the SC50 values of 28.9, 14.0, 13.9 µM in ABTS radical scavenging assay, and 75, 79, and 81 with the SC50 values of 19.2, 15.3, and 28.7 µM in DPPH radical scavenging assay, respectively. Compounds 80, 83, 84, and 85 exhibited anti-inflammatory activity with the Emax values of 77.4, 69.5, 83.0, and 71.3 % in inhibitory effect of nitrite production, respectively.

並列關鍵字

Sassafras randaiense ； Lauraceae ； root ； stem ； anti-tubercular activity ； anti-oxidant activity ； anti-inflammatory activity

參考文獻

1. Liao JC. Lauraceae in Flora of Taiwan. 2nd. Ed. Editorial Committee of the Flora of Taiwan: Taipei, Taiwan; 1996: Vol.Ⅱ: pp. 433–99.

2. Nie ZL, Wen J, Sun H. Phylogeny and biogeography of Sassafras (Lauraceae) disjunct between eastern Asia and eastern North America. Plant Syst Evol 2007; 267: 191–203.

3. Wolfe JA, Wehr, W. Middle Eocene dicotyledonous plants from Republic, northeastern Washington. U S Geol Surv Bull 1597; 13.

4. Lin SL, Guan BT, Hu YW. Leaves attributes of reproductive shoots of Taiwan sassafras (Sassafras randaiense Rehder) at Chilan Shan, northeastern Taiwan. Quar J Chinese For 2013; 46: 27–36.

5. 張峰義、施文儀、周志浩、陳穎慧、莊人祥、楊靖慧. 台灣結核病防治年報 2012. 行政院衛生署疾病管制局 2012; 1–216.