Chemical Constituents of the Root of Dystaenia takeshimana and Their Anti-Inflammatory Activity

  • Kim, Ju-Sun (Natural Products Research Institute and College of Pharmacy, Seoul National University) ;
  • Kim, Jin-Cheul (College of Pharmacy, Yeungnam University) ;
  • Shim, Sang-Hee (Natural Products Research Institute and College of Pharmacy, Seoul National University) ;
  • Lee, Eun-Ju (Natural Products Research Institute and College of Pharmacy, Seoul National University) ;
  • Jin, Wen-Yi (College of Pharmacy, Chungnam National University) ;
  • Bae, Ki-Hwan (College of Pharmacy, Chungnam National University) ;
  • Son, Kun-Ho (Department of Food and Nutrition, Andong National University) ;
  • Kim, Hyun-Pyo (College of Pharmacy, Kangwon National University) ;
  • Kang, Sam-Sik (Natural Products Research Institute and College of Pharmacy, Seoul National University) ;
  • Chang, Hyeun-Wook (College of Pharmacy, Yeungnam University)
  • 발행 : 2006.08.01

초록

In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin $D_2\;(PGD_2)$ and leukotriene $C_4\;(LTC_4)$ in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with ${\beta}-sitosterol$ (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphenyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (10), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was isolated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)- marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids.

키워드

참고문헌

  1. Chang, I. M., Yun, H. S., and Kazuo, Y., Revision of $^{13}C$ NMR assignments of ${\beta}$-sitosterol and ${\beta}$-sitosterol 3-O-${\beta}$-D-glucopyranoside isolated from Plantago asiatica seed. Kor. J. Pharmacogn., 12, 12-14 (1981)
  2. Fiorucci, S., Meli, R., Bucci, M., and Cirino, G.., Dual inhibitors of cyclooxygenase and 5-lipoxygenase. A new avenue in anti-inflammatory therapy? Biochem. Pharmacol., 62, 1433- 1438 (2001) https://doi.org/10.1016/S0006-2952(01)00747-X
  3. Hagiwara, S.-Y., Takahshi, M., Shen, Y., Kaihou, S., Tomiyama, T., Yazawa, M., Tamai, Y., Sin, Y.-S., Kazusaka, A., and Terazawa, M., A Phytochemical in the Edible Tamogi-take Mushroom (Pleurotus cornucopiae), D-Mannitol, Inhibits ACE Activity and Lowers the Blood Pressure of Spontaneously Hypertensive Rats. Biosci. Biotechnol. Biochem., 69, 1603- 1605 (2005) https://doi.org/10.1271/bbb.69.1603
  4. Hisamoto, M., Kikuzaki, H., and Nakatani, N., Constituents of the Leaves of Peucedanum japonicum Thunb. and Their Biological Activity. J. Agric. Food Chem., 52, 445-450 (2004) https://doi.org/10.1021/jf0349127
  5. Jung, H. J., Min, B. S., Park, J. Y., Kim, Y. H., Lee, H. K., and Bae, K., Gymnasterkoreaynes A-F, Cytotoxic Polyacetylenes from Gymnaster koraiensis. J. Nat. Prod., 65, 897-901 (2002) https://doi.org/10.1021/np0104018
  6. Kayser, O. and Kolodziej, H., Highly Oxygenated Coumarins from Pelargonium sidoides. Phytochemistry, 39, 1181-1185 (1995) https://doi.org/10.1016/0031-9422(95)00166-5
  7. Kim, D. K., Antioxidative Components from the Aerial Parts of Lactuca scariloa L. Arch. Pharm. Res., 24, 427-430 (2001) https://doi.org/10.1007/BF02975189
  8. Kim, B. H., Kwon, Y. S., and Kim, C. M., A study on the chemical components from the roots of Dystaenia takeshimana. Saengyak Hakhoechi, 24, 296-298 (1993)
  9. Kim, Y., Min, H.-Y., Park, H. J., Lee, E.-J., Park, E.-J., Hwang, H.-J., Jin, C., Lee, Y.-S., and Lee, S. K., Suppressive effects of nitric oxide production and inducible nitric oxide synthase (iNOS) gene expression by Calystegia soldanella methanol extract on lipopolysaccharide-activated RAW 264.7 cells. Eur. J. Cancer Prevention., 13, 419-424 (2004) https://doi.org/10.1097/00008469-200410000-00010
  10. Kwon, Y. S., Kim, C. W., and Kim, C. M., A study on the chemical components from the roots of Dystaenia takeshimana. Saengyak Hakhoechi, 23, 218-220 (1992)
  11. Lee, Y. N., Flora of Korea, Kyo-Hak Publishing Co., Ltd., Seoul, (1996)
  12. Lee, S. H., Son, M. J., Ju, H. K., Lin, C. X., Moon, T. C., Choi, H. G., Son, J. K., and Chang, H.W., Dual inhibition of cyclooxygenases- 2 and 5-lipoxygenase by deoxypodophyllotoxin in mouse bone marrow-derived mast cells. Biol. Pharm. Bull., 27, 786-788 (2004) https://doi.org/10.1248/bpb.27.786
  13. Lin, C. X., Son, M. J., Ju, H. K., Moon, T. C., Lee, E. K., Kim, S. H., Kim, M. J., Son, J. K., Lee, S. H., and Chang, H. W., Deoxypodophyllotoxin (anthricin), a naturally occurring lignan, inhibits PCA reaction. Planta Med., 70, 474-476 (2004) https://doi.org/10.1055/s-2004-818981
  14. Matsumura, T., Ishikawa, T., and Kitajima, J., Water-soluble constituents of caraway: aromatic compound, aromatic compound glucoside and glucides. Phytochemistry, 61, 455- 459 (2002) https://doi.org/10.1016/S0031-9422(02)00288-1
  15. Murakami, M., Matsumoto, R., Austen, K. F., and Arm, J. P., Prostaglandin endoperoxide synthase-1 and -2 couple to different transmembrane stimuli to generate prostaglandin D2 in mouse bone marrow-derived mast cells. J. Biol. Chem., 269, 22269-22275 (1994)
  16. Murakami, M., Austen, K. F., and Arm, J. P., The immediate phase of c-kit ligand stimulation of mouse bone marrowderived mast cells elicits rapid leukotriene C4 generation through posttranslational activation of cytosolic phospholipase A2 and 5-lipoxygenase. J. Exp. Med., 182, 197-206 (1995) https://doi.org/10.1084/jem.182.1.197
  17. Nes, W. R., Norton, R. A., and Benson, M., Carbon-13 NMR studies on Sitosterol Biosynthesized from ($^{13}C$) Mevalonates. Phytochemistry, 31, 805-811 (1992) https://doi.org/10.1016/0031-9422(92)80165-B
  18. Park, J. Y., Min, B. S., Jung, H. J., Kim, Y. H., Lee, H. K., and Bae, K., Polyacetylene glycosides from Gymnaster koraiensis. Chem. Pharm. Bull., 50, 685-687 (2002) https://doi.org/10.1248/cpb.50.685
  19. Sasaki, H., Taguchi, H., Endo, T., and Yosioka, I., The Constituents of Glehnia littoralis FR. SCHMIDT et MIQ. Structure of a New Coumarin Glycoside, Osthenol 7-O-${\beta}$-gentiobioside. Chem. Pharm. Bull., 28, 1847-1852 (1980) https://doi.org/10.1248/cpb.28.1847
  20. Shin, K. H., Kang, S. S., Seo, E. A., and Shin, S. W., Isolation of Aldose Reductase Inhibitors from the Flowers of Chrysanthemum boreale. Arch. Pharm. Res., 18, 65-68 (1995) https://doi.org/10.1007/BF02979135
  21. Taniguchi, M., Yanai, M., Xiao, Y. Q., Kido, T., and Baba, K., Three Isocoumarins from Coriandrum sativum. Phytochemistry, 42, 843-846 (1996) https://doi.org/10.1016/0031-9422(95)00930-2
  22. Thuong, P. T., Na, M. K., Su, N. D., Seong, R. S., Lee, Y. M., Sok, D. E., and Bae, K., Inhibitory Effect of Coumarins from Weigela subsessilis on Low Density Lipoprotein Oxidation. Biol. Pharm. Bull., 28, 1095-1097 (2005) https://doi.org/10.1248/bpb.28.1095
  23. Tsukamoto, H., Hisada, S., Nishibe, S., Roux, D. G., and Rourke, J. P., Coumarins from Olea africana and Olea capensis. Phytochemistry, 23, 699-700 (1984) https://doi.org/10.1016/S0031-9422(00)80417-3