DOI QR코드

DOI QR Code

Isolation and Characterization of Constituent Compounds from Leaves and Stems of Chrysanthemum boreale Makino

산국 잎과 줄기의 유효성분 분리 및 특성 연구

  • Park, Sook Jahr (Department of Pharmaceutical Engineering, Daegu Haany University) ;
  • Park, Moon Ki (Department of Pharmaceutical Engineering, Daegu Haany University) ;
  • Lee, Jong Rok (Department of Pharmaceutical Engineering, Daegu Haany University)
  • 박숙자 (대구한의대학교 제약공학과) ;
  • 박문기 (대구한의대학교 제약공학과) ;
  • 이종록 (대구한의대학교 제약공학과)
  • Received : 2019.10.18
  • Accepted : 2019.11.15
  • Published : 2019.11.30

Abstract

Chrysanthemum boreale Makino (C. boreale) is widely distributed in Asian countries, and has traditionally been used to treat various inflammatory diseases including bronchitis. In this study, we aimed to isolate biologically active compounds from leaves and stems of C. boreale. Chemical components were purified by column chromatograpy and recyclic HPLC, and characterized from their spectral data (IR, MS, NMR). Biological activity experiments were conducted for Farnesyl-protein transferase (FPTase) activity, apoptosis and nitirc oxide (NO) release. As a results, three sesquiterpene lactones were isolated. Compound 1 (4-methoxy-8-O-acetyl-10-hydroxy-2,11(13)-guaiadiene-12,6-olide) showed strong cytotoxic activities having an average growth inhibition of 50% ($GI_{50}$) value of $1.89{\mu}g/m{\ell}$ against human colon adenocarcinoma cells. Compound 1 also showed a low half maximal inhibitory concentration ($IC_{50}$) value of $10{\mu}g/m{\ell}$ for NO release. In the caspase 3 activity, compound 1 and compound 2 (8-O-(2-carbonyl-2-butyl)-3,10-dihydroxy-4,11(13) -guaiadiene-12,6-olide) exhibited 94% and 90% apoptosis inhibition activity, respectively. Compound 3 (4,8-O-diacetyl -10-hydroxy-2(3),11(13)-guaiadiene-12,6-olide) showed a strong inhibitory effect on FPTase activity with 90% inhibitory activity at a concentration of $100{\mu}g/m{\ell}$. These results clearly show the presence of lactone compounds in the leaves and stems, which may partially contribute to the pharmacological activity of C. boreale.

References

  1. Ahn, B. Z., Sok, D. E., 1996, Michael acceptor as a tool for anticancer drug design, Curr. Pharm. Design., 2, 247-262.
  2. Barnes, P. J., Liew, F. Y., 1995, Nitric oxide and asthmatic inflammation, Immunol. Today, 16(3), 128-130. https://doi.org/10.1016/0167-5699(95)80128-6
  3. Bensky, D., Gamble, A., Kaptchuk, T., 1986, Chinese herbal medicine: Materia Medica, Eastland press, Seattle, 59.
  4. Elmore, S., 2007, Apoptosis: a review of programmed cell death, Toxicol. Pathol., 35(4), 495-516. https://doi.org/10.1080/01926230701320337
  5. Fink, S. L., Cookson, B. T., 2005, Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells, Infect. Immun., 73(4), 1907-1916. https://doi.org/10.1128/IAI.73.4.1907-1916.2005
  6. Fraga, B. M., 2012, Natural sesquiterpenoids, Nat. Prod. Rep., 29(11), 1334-1366. https://doi.org/10.1039/c2np20074k
  7. Grivennikov, S. I., Greten, F. R., Karin, M., 2010, Immunity, inflammation, and cancer, Cell, 140(6), 883-899. https://doi.org/10.1016/j.cell.2010.01.025
  8. Giordano, O. S., Querreiro, E., Pestchanker, M. J., Guzman, J., Pastor, D., Guardia, T., 1990, The gastric cytoprotective effect of several sesquiterpene lactones, J. Nat. Prod., 53(4), 803-809. https://doi.org/10.1021/np50070a004
  9. Han, W. S., 2003, Isolation and structure elucidation of radical scavengers from Chrysanthemum boreale Makino, Kor. J. Med. Crop. Sci., 11(1), 1-4.
  10. Jang, D. S., Park, K. H., Ko, H. L., Lee, H. S., Kwon, B. M., Yang, M. S., 1998, Biological activities of sesquiterpene lactones isolated from several compositae plants. Part 3. Inhibitory activity on nitric oxide release and ACAT, Kor. J. Pharmacogn., 29(3), 243-247.
  11. Jang, D. S., Park, K. H., Yang, M. S., 1998a, Germacranolides from flowers of Chrysanthemum boreale Makino, Kor. J. Pharmacogn., 29(2), 67-70.
  12. Janice, E. B., James, C. M., 1995, Farnesyl transferase inhibitors: the successes and surprises of a new class of potential cancer chemotherapeutics, Chem. Biol., 2(12), 789-791.
  13. Kang, S. S., Kim, J. S., Son, K. H., Lee, C. O., Kim, Y. H., 1996, Isolation of handelin from Chrysanthemum boreale, Arch. Pharm. Res., 19(5), 406-410. https://doi.org/10.1007/BF02976387
  14. Kim, B. S., Park, S. J., Kim, M. K., Kim, Y. H., Lee, S. B., Lee, K. H., Choi, N. Y., Lee, Y. R., Lee, Y. E., You, Y. O., 2015, Inhibitory effects of Chrysanthemum boreale essential oil on biofilm formation and virulence factor expression of Streptococcus mutans, Evid. Based Complement. Altern. Med., 2015, 616309.
  15. Kim, D. Y., Hwang, D. I., Yoon, M. S., Choi, I. H., Lee, H. M., 2016, Effect of hydrosol extracted from Chrysanthemum boreale Makino flower on proliferation and migration in human skin keratinocyte, J. Soc. Cosmet. Sci. Korea, 42(1), 95-101. https://doi.org/10.15230/SCSK.2016.42.1.95
  16. Kim, D. Y., Won, K. J., Yoon, M. S., Hwang, D. I., Yoon, S. W., Park, J. H., Kim, B., Lee, H. M., 2015a, Chrysanthemum boreale Makino essential oil induces keratinocyte proliferation and skin regeneration, Nat Prod Res., 29(6), 562-564. https://doi.org/10.1080/14786419.2014.952231
  17. Kim, D. Y., Won, K. J., Yoon, M. S., Yu, H. J., Park, J. H., Kim, B., Lee, H. M., 2015b, Chrysanthemum boreale flower floral water inhibits platelet-derived growth factor-stimulated migration and proliferation in vascular smooth muscle cells, Pharm. Biol., 53(5), 725-734. https://doi.org/10.3109/13880209.2014.941882
  18. Kim, K. J., Kim, Y. H., Yu, H. H., Jeong, S. I., Cha, J. D., Kil, B. S., You, Y. O., 2003, Antibacterial activity and chemical composition of essential oil of Chrysanthemum boreale, Planta Med., 69(3), 274-277. https://doi.org/10.1055/s-2003-38479
  19. Kim, T. J., 1996, Korean resources plants IV, Seoul National Univ. Press, Seoul, 259.
  20. Kim, T. K., Ock, C. Y., Lee, J. S., Hahm, K. B., 2009, Implication of TGF-${\beta}$ in pathway connecting inflammation and carcinogenesis, Cancer Prev. Res., 14, 177-187.
  21. Kim, Y. H., Sung, J. H., Sung, M. S., Choi, Y. M., Jeong, H. S., Lee, J. S., 2010, Involvement of heme oxygenase1 in the anti-inflammatory activity of Chrysanthemum boreale Makino extracts on the expression of inducible nitric oxide synthase in RAW264.7 macrophages, J. Ethnopharmacol., 131(3), 550-554. https://doi.org/10.1016/j.jep.2010.07.030
  22. Ko, K. S., 1991, Coloured wild plants of Korea. Academy Press., Seoul, 32.
  23. Lee, C. H., 1985, Illustrated encyclopedia of flora in Korea. Hyangmoonsa, Seoul, 648.
  24. Lee, J. R., Park, M. K., 2017, Isolation of guaianolides with ACAT inhibitory activity from the leaves and stems of Chrysanthemum boreale Makino, J. Environ. Sci. Int., 26(11), 1275-1284. https://doi.org/10.5322/JESI.2017.26.11.1275
  25. Lee, J. R., Park, M. K., 2017a, Structural analysis and biological activities of sesquiterpene lactones isolated from the leaves and stems of Chrysanthemum boreale Makino, J. Environ. Sci. Int., 26(11), 1285-1295. https://doi.org/10.5322/JESI.2017.26.11.1285
  26. Lowenstein, C. J., Dinerman, J. L., Synder, S. H., 1994, Nitric oxide: a physiologic messenger, Ann. Intern. Med., 120(3), 227-237. https://doi.org/10.7326/0003-4819-120-3-199402010-00009
  27. Matthias, H., Kurt, H., 1991, Bioactivity in plant: The link between phytochemistry and medicine, Phytochemistry, 30(12), 3864-3874. https://doi.org/10.1016/0031-9422(91)83425-K
  28. Sporel, J., Becker, H., Allen, N. S., Gupta, M. P., 1991, Spiroterpenoids from Plagiochila moritziana, Phytochemistry, 30(9), 3043-3047. https://doi.org/10.1016/S0031-9422(00)98249-9
  29. Yang, G., Lee, K., An, D. G., Lee, M. H., Ham, I. H., Choi, H. Y., 2012, Effect of Chrysanthemi borealis flos on atopic dermatitis induced by 1-chloro 2,4-dinitrobenzene in NC/Nga mouse, Immunopharmacol. Immunotoxicol., 34(3), 413-418. https://doi.org/10.3109/08923973.2011.613401