题名

苦蘵有效成分化學製備與分析

并列篇名

Chemical Preparation and Analyses of Active Principles from Physalis angulata

作者

柯泓瑋

关键词

苦蘵 ; Physalin ; Physalis angulata ; Physalin

期刊名称

高雄醫學大學天然藥物研究所碩士班學位論文

卷期/出版年月

2017年

学位类别

碩士

导师

張芳榮

内容语文

繁體中文

中文摘要

本研究探討從不同溶媒萃取方式,建立苦蘵活性指標化合物 physalins產率最佳化之萃取及製程。利用最有效的溶媒萃取、濃縮、快速分離,進一步研究萃取物中四種活性指標成分physalin B、physalin C、physalin F與physalin U之定性、定量評估,及探討在不同保存條件下化合物physalins成分之安定性。此研究提供一個具代表性的化學指紋圖譜、建立苦蘵活性成分品質管理平台,及其有效的保存方法,在未來可應用於苦蘵相關產品之管控。 透過核磁共振(NMR)光譜數據分析以及比對文獻上四個已知physalins,並將四個化合物分別進行A549、MDA-MB-231和HepG2人類細胞株之細胞毒殺篩選。其中化合物physalin F (3)對上述細胞株最具有細胞毒殺作用(IC50 = 0.56‒0.67 μg/mL) 。

英文摘要

In this investigation, we report a convenient method for concentrating the physalin-rich fraction, from different kinds of the solvent extraction design on Physalis angulata. The concentrate of four major active ingredients in optimization preparation was identified. Efficient extraction, concentration, and rapid analyses methods provide necessary information for quality control assessment of physalins B, physalin C, physalin F, and physalin U. In addition, the stability for qualitative changes of the components is further explored for the advance management for mass production of this plant material. The structures of the isolated compounds were elucidated by the analyses of NMR spectral data. The four major components 1−4 of P. angulata were tested for their cytotoxicity against A549, MDA-MB-231, and HepG2 cell lines. Among all tested compounds, physalin F (3) is the most potent compound with the IC50 values ranged from 0.56 to 0.67 μg/mL against aforementioned cancer cell lines.

主题分类 醫藥衛生 > 藥理醫學
藥學院 > 天然藥物研究所碩士班
参考文献
  1. 1. Khan, I. and T. Smillie, Implementing a 'quality by design' approach to assure the safety and integrity of botanical dietary supplements. J. Nat. Prod,, 2012. 28, 1665-1673.
    連結:
  2. 2. Molinari, G., Natural products in drug discovery: present status and perspectives. . Adv. Exp. Med. Biol., 2009. 655, 13–27.
    連結:
  3. 3. Newman, D.J. and G.M. Cragg, Natural products as sources of new drug over the last 25 years. J. Nat. Prod., 2007. 70, 461–477.
    連結:
  4. 4. Newman, D.J. and G.M. Cragg, Natural products as sources of new drug over the 30 years from 1981 to 2010. J. Nat. Prod., 2007. 75, 311–335.
    連結:
  5. 7. Lin, Y.S., H.C. Chiang, W.S. Kan, E. Hon, S.J. Shih, and M.H. Won, Immunomodulatory activity of various fractions derived from Physalis angulata L extract. Am J Chin Med., 1992. 20, 233–243.
    連結:
  6. 8. 許嘉純, 苦蘵抗黑色素瘤及抗血小板活性之研究. 2016. 高雄醫學大學天然藥物研究所.
    連結:
  7. 11. Sun, C.P., C.Y. Qiu, T. Yuan, X.F. Nie, and H.X. Sun, Antiproliferative and anti-inflammatory withanolides from Physalis angulata. J. Nat. Prod., 2016. 79, 1586–1597.
    連結:
  8. 12. Jin, Z., M.S. Mashuta, and N.J. Stolowich, Physangulidines A, B, and C: Three new antiproliferative withanolides from Physalis angulata L. Org. Lett., 2012. 14, 1230−1233.
    連結:
  9. 13. Shingu, Yahara, Nohara, and Okabe., Three new withanolides, physagulins A, B and D from physalis angulata L. Chem. Pharm. Bull., 1992. 40, 2088−2091.
    連結:
  10. 14. Nagafuji, Shinya, Okabe, Hikaru, and Akahane, Fumiko. Trypanocidal constituents in Plants 4. Withanolides from the Aerial Parts of Physalis angulata. . Biol. Pharm. Bull., 2004. 27, 193−197.
    連結:
  11. 15. Ting, M., N.Z. Wen, and Y. Lei, Cytotoxic withanolides from Physalis angulata var. villosa and the apoptosis-inducing effect via ROS generation and the activation of MAPK in human osteosarcoma cells. RSC Adv., 2016. 6, 53089−53100
    連結:
  12. 16. Chen, C.M., Z.T. Chen, C.H. Hsieh, W.S. Li, and S.Y. Wen, Withangulatin A, a New Withanolide from Physalis angulata. Chem. Pharm. Bull., 1992. 40, 2088−2091.
    連結:
  13. 17. Ankrag, N.A., A.K. Nyarko, P.G. Addo, M. Ofosuhene, C. Dzokoto, E. Marley, M.M. Addae, and F.A. Ekuban, Evaluation of efficacy and safety of a herbal medicine used for the treatment of malaria. Phytother Res. , 2003. 17, 697–701.
    連結:
  14. 18. Damu, A.G., P.C. Kuo, C.R. Su, T.H. Kuo, T.H. Chen, K.F. Bastow, K.H. Lee, and T.S. Wu, Isolation, structures, and structure-cytotoxic activity relationships of withanolides and physalins from Physalis angulata. J. Nat. Prod., 2007. 70, 1146−1152.
    連結:
  15. 19. Gottlieb, H.E., M. Cojocaru, S.C. Sinha, M. Saha, and A. Bagchi, Withaminimin, a withanolide from physalis minima. Phytochemistry., 1987. 26, 1801−1804.
    連結:
  16. 20. Maldonado, E., N.E. Hurtado, A.L. Pérez-Castorena, and M. Martínez, Cytotoxic 20,24-epoxywithanolides from Physalis angulata. Steroids., 2015. 104, 72–78.
    連結:
  17. 21. Vasina, O.E., N.D. Abdullaev, and N.K. Abubakirov, Withasteroids of Physalis. VIII. Vamonolide. Chem. Nat. Compd. , 1987. 23, 712 −714.
    連結:
  18. 22. Matsuura, T., M. Kawai, R. Makashima, and Y. Butsugan, Structures of physalin A and physalin B, 13,14-seco-16,24-cyclo-steroids from Physalis alkekengi var. Francheti. . J. Chem. SOC., 1970. 5, 664 −670.
    連結:
  19. 23. Kawai, M., M. Taga, and F. Yamamoto, Crystal structures of 5α,6α-epoxy and 2,3-dihydro derivatives of physalin b, a 13,14-seco-16,24-cyclosteroid, and their 1h nmr spectral analysis. Bull. Chem. Soc. Jpn, 1994. 67, 222−226.
    連結:
  20. 24. Jacobo-Herrera, N.J., P. Bremner, N. Marquez, M.P. Gupta, S. Gibbons, E. Munoz, and M. Heinrich, Physalins from Witheringia solanacea as modulators of the NF-κB cascade. J. Nat. Prod., 2006. 69, 328−331.
    連結:
  21. 25. Row, L.R., N.S. Sarma, T. Matsuura, and R. Nakashima, Physalins E and H, new physalins from Physalis angulata and P. lancifolia. . Phyochemrstry., 1978. 17, 1641−1645.
    連結:
  22. 26. Makino, B., M. Kawai, Y. Iwata, H. Yamamura, Y. Butsugan, K. Ogawa, and M. Hayashi, Physalins possessing an endoperoxy structure from Physalis alkekengi var. francheti. structural revision of physalin K. . Bull. Chem. Soc. Jpn., 1995. 68, 219−226.
    連結:
  23. 27. Cheng, P.S., T. Yuan, L. Wang, N. Kang, F. Zhao, L.X. Chen, and Q. Feng, Anti-inflammatory labdane-type diterpenoids from Physalis angulata. RSC Adv. , 2016. 6, 76838–76847.
    連結:
  24. 28. Ismail, N. and M. Alam, A novel cytotoxic flavonoid glycoside from Physalis angulata. Fitoterapia, 2001. 72, 676−679.
    連結:
  25. 29. Fumiko, A., N. Shinya, O. Masafumi, and K. Junei, Trypanocidal constituents in plants minor withanolides from the aerial parts of Physalis angulata. Chem. Pharm. Bull., 2006. 54, 1226−1228.
    連結:
  26. 30. Asano, N., A. Kato, H. Kizu, and K. Matsui, 1β-Amino-2α,3β,5β-trihydroxy- cycloheptane from Physalis alkekengi var. francheti. . Phytochemistry., 1996. 42, 719−721.
    連結:
  27. 31. Ramachandra, R.L., S.N. Subrahmanya, M. Teruo, and N. Ruka, Physalins E and H, new physalins from Physalis angualra and P. lancifolia. Phyochemistry., 1978. 17, 1641−1645.
    連結:
  28. 32. Freiburghaus, F., R. Kaminsky, M.H. Nkunya, and R. Burn, Evaluation of African medicine plants for their in vitro trypanocidal activity. J Ethnopharmacol., 1996. 55, 1–11.
    連結:
  29. 33. Pietro, R.C., S. Kashima, D.N. Sato, A.H. Januario, and S.C. Franca, In vitro antimycobacterial activities of Physalis angulata L. Phytomedicine., 2000. 7, 335–338.
    連結:
  30. 35. Wu, S.J., L.T. Ng, C.H. Chen, D.L. Lin, S.S. Wang, and C.C. Lin, Antihepatoma activity of Physalis angulata and P. peruviana extract and their effects on apoptosis in human Hep G2 cells. Life Sci., 2004. 74, 2061–2073.
    連結:
  31. 36. Hsieh, W.T., K.Y. Huang, H.Y. Lin, and J.G. Chang, Physalis angulata induced G2/M phase arrest in human breast cancer cells. Food Chem Toxicol., 2006. 44, 974–983.
    連結:
  32. 37. Hsu, C.C., Y.C. Wu, L. Farh, Y.C. Du, W.K. Tseng, C.C. Wu, and F.R. Chang, Physalin B from Physalis angulata triggers the NOXA-related apoptosis pathway of human melanoma A375 cells. Food Chem. Toxicol., 2012. 50, 619–624.
    連結:
  33. 38. Wu, S.Y., Y.L. Leu, Y.L. Chang, T.S. Wu, P.C. Kuo, Y.R. Liao, C.M. Teng, and S.L. Pan, Physalin F induces cell apoptosis in human renal carcinoma cells by targeting NF-kB and generating reactive oxygen species. PLOS ONE, 2012. 7, e40727.
    連結:
  34. 41. 黃乙欣, 超臨界、超音波及微波萃取法在生物資源之應用與差異化比較. 2014. 南台科技大學生物科技系.
    連結:
  35. 5. Heish, C.F. and T.C. Huang, Flora of Taiwan. 4, 535.
  36. 6. Kambuou, R.N., Country report to the FAO international technical conference on plant genetic resources. 1996, Konedobu.
  37. 9. 徐瑞成, 燈籠草(Physalis angulata L.)所含Physalins之結構研究. 1998. 國立清華大學化學所.
  38. 10. 黃寬裕, 苦蘵引起人類乳癌細胞G2/M期停滯和細胞凋亡. 2004. 中國醫藥大學醫學研究所.
  39. 34. Chiang, H.C., S.M. Jaw, C.F. Chen, and W.S. Kan, Antitumor agent, physalin F from Physalis angulata L. . Anticancer Res., 1992. 12, 837–843.
  40. 39. 張楠, 儲小琴, and 蔣建勤, 錦燈籠醋酸乙酯部位化學成分的研究. Chin. Tradit. Herb. Drugs., 2015. 46, 1120-1124.
  41. 40. Makino, B., M. Kawai, H. Yamamura, S. Araki, and Y. Butsugan, Tautomerism between exomethylene type physalins and oxymethylene-bridged physalins. . Pharmazie., 2002. 57, 215−216.
  42. 42. 衛署藥字第87041838號.
  43. 43. 郭俊宏, 利用高效能液相層析質譜法鑑定六種桑寄生科植物之研究. 2008. 朝陽科技大學應用化學系.