Triterpenoids from the Flower of Campsis grandiflora K. Schum. As Human Acyl-CoA: Cholesterol Acyltransferase Inhibitors

  • Kim, Dong-Hyun (Graduate School of Biotechnology & Plant Metabolism Research Center, Kyung Hee University) ;
  • Han, Kyung-Min (Graduate School of Biotechnology & Plant Metabolism Research Center, Kyung Hee University) ;
  • Chung, In-Sik (Graduate School of Biotechnology & Plant Metabolism Research Center, Kyung Hee University) ;
  • Kim, Dae-Keun (Department of Pharmacy, Woosuk University) ;
  • Kim, Sung-Hoon (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kwon, Byoung-Mog (Korea Research Institute of Bioscience and Biotechnology) ;
  • Jeong, Tae-Sook (Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Mi-Hyun (Erom life Co. Ltd.) ;
  • Ahn, Eun-Mi (Scigenic Co. Led.) ;
  • Baek, Nam-In (Graduate School of Biotechnology & Plant Metabolism Research Center, Kyung Hee University)
  • Published : 2005.01.01

Abstract

The flower of Campsis grandiflora K. Schum. Was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and H$_2$O. From the EtO Ac fraction, seven triterpenoids were isolated through the repeated silica gel, ODS column chromatographies and preparative HPLC. From the result of physico- chemical data including NMR, MS and IR, the chemical structures of the compounds were determined as 3${\beta}$-hydroxyolean-12-en-28-oic acid (oleanolic acid, 1), 3${\beta}$-hydroxyurs-12-en-28-oic acid (ursolic acid, 2), 3${\beta}$-hydroxyurs-12-en-28-al (ursolic aldehyde, 3), 2${\alpha}$,3${\beta}$-dihydroxyolean-12-en-28-oic acid (maslinic acid, 4), 2${\alpha}$,3${\beta}$-dihydroxyurs-12-en-28-oic acid (corosolic acid, 5), 3${\beta}$,23-dihydroxyurs-12- en-28-oic acid (23-hydroxyursolic acid ,6) and 2${\alpha}$,3${\beta}$,23-trihydroxyolean-12-en-28- oic acid (arjunolic acid, 7). These teriterpenoids were isolated for the first time from this plant. Also, compounds 4, 5, 6, and 7 revealed relatively high hACAT-1 inhibitory activity with the value of 46.2${\pm}$1.1, 46.7${\pm}$0.9, 41.5${\pm}$1.3 and 60.8${\pm}$1.1% at the concentration of 100${\mu}$g/mL, respectively.

Keywords

References

  1. Abdullahi, H., Nyandat, E., Galeffi, C., Messana, I., Nicoletti, M., and Bettolo, G. B., Cyclohexanols of Halleria lucida. Phytochemistry, 25, 2821-2823 (1986) https://doi.org/10.1016/S0031-9422(00)83749-8
  2. Accad, M., Smith, S. J., Newland, D. L., Sanan, D. A., King, L. E. Jr., Linton, M. F., Fazio, S., and Farese, R., Jr., Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA: cholesterol acyltransferase 1. J. Clin. Invest., 105, 711-719 (2000) https://doi.org/10.1172/JCI9021
  3. Anderson, R. A., Joyce, C., Davis, M., Reagan, J. W., Clark, M., Shelness, G. S., and Rudel L. L., Identification of a form of Acyl-CoA: Cholesterol acyltransferase specific to liver and intestine in nonhuman primates. J. Biol. Chem., 273, 26747- 26754 (1998) https://doi.org/10.1074/jbc.273.41.26747
  4. Brecher, P. and Chan, C. T., Properties of acyl-CoA:Cholesterol O-acyltransferase in aortic microsomes from atherosclerotic rabbits. Biochem. Biophys. Acta, 617, 458-471 (1980) https://doi.org/10.1016/0005-2760(80)90012-0
  5. Brown, M. S., Dana, S. E., and Goldstein, J. L., Cholsterol ester formation in cultured human fibroblasts. J. Biol. Chem., 250, 4025-4027 (1975)
  6. Buhman, K. K., Accad, M., Novak, S., Choi, R. S., Wong, J. S., Hamilton, R. L., Turley, S., and Farese, R. V., Jr., Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nat. Med., 6, 1341-1347 (2000) https://doi.org/10.1038/82153
  7. Coses, S., Novak, S., Zheng, Y., Myers, H. M., Lear, S. R., Sande, E., Welch, C. B., Lusis, A. J., Spancer, T. A., Krouse, B. R., Erickson, S. K., Jr., and Farese, R. V., Jr., ACAT-2, a second mammalian acyl-CoA: Cholesterol acyltransferase. J. Biol. Chem., 273, 26755-26764 (1998) https://doi.org/10.1074/jbc.273.41.26755
  8. Dommick, M. A., Mcguire, E. J., Reindel, J. F., Bobrowski, W. F., Bocan, T. M., and Gough, A. W., Subacute toxicity of a novel inhibitor of acyl-CoA: cholesterol acyltransferase in beagle dogs. Fundam. Appl. Toxicol., 20, 217-224 (1993) https://doi.org/10.1006/faat.1993.1029
  9. Houghton, P. J. and Lian, L. M., Triterpenoids from Desfontainia spinosa. Phytochemistry, 25, 1939-1944 (1986) https://doi.org/10.1016/S0031-9422(00)81179-6
  10. Imakura, Y., Kobayashi, S., Kida, K., and Kido, M., Iridoid glucosides from Campsis chinensis. Phytochemistry, 23, 2263-2269 (1984) https://doi.org/10.1016/S0031-9422(00)80532-4
  11. Imakura, Y., Kobayashi S., and Mima, A., Bitter phenyl propanoid glycosides from Campsis chinensis. Phytochemistry, 24, 139-146 (1985) https://doi.org/10.1016/S0031-9422(00)80823-7
  12. Imakura, Y., Kobayashi, S., Yamahara, Y., Kihara, M., Tagawa, M., and Murai, F., Studies on constituents of Bignoniaceae plants. IV. Isolation and structure of a new iridiod glucoside, campsiside from Campsis chinensis. Chem. Pharm. Bull., 33, 2220-2227 (1985) https://doi.org/10.1248/cpb.33.2220
  13. Jeong, T. S., Kim, S. U., Son, K. H., Kwon, B. M., Kim, Y. K., Choi, M. U., and Bok, S. H., GERI-BP001 compounds, new inhibitors of acyl-CoA:Cholesterol acytransferase from Aspergillus fumigatus F37. J. Antibiot., 48, 751-756 (1995) https://doi.org/10.7164/antibiotics.48.751
  14. Joyce, C. W., Shelness, G. S., Davis, M. A., Lee, R. G., Skinner, K., Anderson, R. A., Rudel, L. L., ACAT1 and ACAT2 membrane topology segregates a serine residue essential for activity to opposite sides of the endopasmic reticulum membrane. Mol. Biol. Cell, 11, 3675-3687 (2000) https://doi.org/10.1091/mbc.11.11.3675
  15. Kim, Y. K., Tomoda, H., and Nishida, H., Pyripyropenes, novel inhibitors of acyl-CoA:Cholesterol acyltransferase produced by Aspergillus fumigatus. J. Antibiot., 47, 154-162 (1994) https://doi.org/10.7164/antibiotics.47.154
  16. Kuang, H. X., Kasai, R., Ohtani, K., Liu, Z. S., Yuan, C. S., and Tanaka, O., Chemical constituents of pericarps of Rosa davurica Pall., a Traditional Chinese medicine. Chem. Pharm. Bull., 37, 2232-2233 (1989) https://doi.org/10.1248/cpb.37.2232
  17. Lee, C. H., Jeong, T. S., Choi, Y. K., Hyun, B. W., Oh, G. T., Kim, E. H., Kim, J. R., Han, J. I., and Bok, S. H., Anti-atherogenic effect of citrus flanonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP- 1 in high cholesterol-fed rabits. Biochem. Biophys. Res. Commun., 284, 681-688 (2001) https://doi.org/10.1006/bbrc.2001.5001
  18. Matsuo, M., Hashimoto, M., Suzuki, J., Iwanami, K., Tomoi, M., and Shimomura, K., Difference between normal and WHHL rabbits in susceptibility to the adrenal toxicity of an Acyl-CoA: Cholesterol acyltransferase inhibitor, FR145237. Toxicol. Appl. Pharmacol., 140, 387-392 (1996) https://doi.org/10.1006/taap.1996.0235
  19. Roth, B. D., Blankley, J., and Hoefle, M. L., Inhibitors of acyl- CoA: Cholesterol acyltransferase. 1. Identification and structure-activity relationships of a novel series of fatty acid anilide hypocholesterolemic agents. J. Med. Chem., 35, 1609-1617 (1992) https://doi.org/10.1021/jm00087a016
  20. Rudel, L. L., Lee, R. G., and Cockman, T. L., Acyl coenzyme A: cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis. Curr. Opin. Lipidol., 12, 121-127 (2001) https://doi.org/10.1097/00041433-200104000-00005
  21. Shim, J. T., Park, K. M., Chung, J. Y., and Hwang, J. K., Antibacterial activity of oleanolic acid from Physalis angulata against oral pathogens. Nutraceuticals & Food, 7, 215-218 (2002)
  22. Sliskovic, D. R., Picard, J. A., and Krause, B. R., 3 ACAT inhibitors: The search for a novel and effective treatment of hypercholesterolemia and atherosclerosis. Prog. Med. Chem., 39, 121-171 (2002) https://doi.org/10.1016/S0079-6468(08)70070-5
  23. Soka, T., Encyclopedia of Chinese Medicines, In Shanghai Science and Technology Publishing Co. (1st Ed.), Sogakukan, Tokyo, pp. 2706-2707 (1985)
  24. Srivastava, S. K. and Jain, D. C., Triterpenoid saponins from plants of Araliaceae. Phytochemistry, 28, 644-647 (1989) https://doi.org/10.1016/0031-9422(89)80074-3
  25. Takemoto, T., Arihara, S., Yoshikawa, K., Kusumoto, K., Yamo, I., and Hayashi, T., Studies on the constituents of Cucurbitaceae plants. VI. On the saponin constituents of Luffa cylindrica Roem. Yakugaku Zasshi, 104, 246-255 (1984) https://doi.org/10.1248/yakushi1947.104.3_246
  26. Ueyama, Y., Hashimoto, S., and Furukawa K., The essential oil from the flowers of Campsis grandiflora (Thumb.) K. Schum. from China. Flavour and Fragrance J., 4, 103-107 (1989) https://doi.org/10.1002/ffj.2730040304
  27. Yagyu, H., Kitamine, T., Osuga, J., Tozawa, R., Chen, Z., Kaji, Y., Oka, T., Perry, S., Tamura, Y., Ohashi, K., Okazaki, H., Yahagi, N., Shionori, F., Iizuka, Y., Harada, K., Shimano, H., Yamashita, H., Gotoda, T., Yamamda, N., and Ishibashi, S. J., Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia. J. Biol. Chem., 275, 21324-21330 (2000) https://doi.org/10.1074/jbc.M002541200