生物活性導向分離土田七(Stahlianthus thorelii) 之抗癌代謝物

Nham-Linh Nguyen、Thanh-Hoa Vo、林玉麒、廖家慶、林志虎、陳美全、郭曜豪

衛福部國家中醫藥研究所 台北醫學大學 中國醫藥大學 嘉義大學

土田七(Stahlianthus thorelii)在民間為廣泛用於治療炎症、癌症、與退化性關節炎之草藥。我們將來自越南的土田七植物的地下莖部，經過乙醇萃取後利用生物活性導向分離法進行分離純化，獲得二個新的酚類化合物，thorechalcone 1與2，與八個已知類似化合物3-10。所有化合物以癌細胞株包含A549、MCF-7、WiDr、與HepG2，進行細胞毒活性篩選，發現化合物1和3對於WiDr, A549, 和HepG2具有抗癌作用。化合物1對肝癌細胞株 (HepG2) 具有最顯著之抑制細胞增生效果，接著進一步進行細胞週期測試，發現在濃度12.5 mM具有最佳效果。所有分離出的化合物皆以核磁共振儀(NMR)與質譜儀(MS)方法進行化學結構鑑定，而化合物1與3更加上以IR、UV、與X-ray方法進行化學結構解析。再者，利用主要成分4與5，以HPLC-DAD進行定量方法的探討，其簡單、精確與快速的 HPLC方法，有助於土田七植物發展為藥物時之有效品質管控。

Bioassay-guided isolation of anticancer metabolites from Stahlianthus thorelii

Nham-Linh Nguyen, Thanh-Hoa Vo, Yu-Chi Lin , Chia-Ching Liaw, Zhi-Hu Lin, Mei-Chuan Chen, and Yao-Haur Kuo

¹   Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei 11221, Taiwan

²   The Ph.D.program in Clinical Drug Development of Chinese Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan

³   Graduate Institute of Intergrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan

⁴   Department of Biochemical Science and Technology, National Chiayi University, Chiayi 60004, Taiwan

*   Correspondence: Prof. Yao-Haur Kuo, Email: kuoyh@nricm.edu.tw, Tel: +886-2-28201999#7061; Fax: +886-2-28236150; Assoc. Prof. Mei-Chuan Chen, E-mail:mcchen1250@tmu.edu.tw

In folk medicine, Stahlianthus thorelii Gagnep. has been used to treat diseases related to inflammation, ulcers, and cancer. This study aims to explore the phytochemicals, quantify the main compounds, and test the anti-cancer activity of isolates from S. thorelii.  Dried rhizomes were extracted with 95% ethanol and then partitioned, fractionated, isolated. Based on the result of the anticancer activity of the fractions, ten isolates were yielded and were identified by spectroscopic analyses. Seven compounds containing two new C-benzylated dihydrochalcone derivatives, thorechalcone A (1) and (2), and the known eight compounds were isolated from S. thorelii. In terms of the bioactivity, compounds 1 and 3 displayed promising anticancer activity (WiDr, A549, and HepG2), with IC₅₀ values < 40 µM. Thorechalcone A (1) showed the most anti-proliferative effect on HepG2 cells and was further evaluated its effect on cell cycle progression at 12.5 mM. The HPLC-UV method of quantification of two major compounds (3 and 4) was also validated. This study presented the isolations of anticancer potentials of new chalcone and known flavonoid derivatives from S. thorelii. The validated simple, accurate, and rapid HPLC method could be deployed for the quality control of herbal drugs.