Browse > Article

Acyl-CoA: Cholesterol Acyltransferase Inhibitors from llex macropoda  

Im Kyung-Ran (Korea Research Institute of Bioscience and Biotechnology)
Jeong Tae-Sook (Korea Research Institute of Bioscience and Biotechnology)
Kwon Byoung-Mog (Korea Research Institute of Bioscience and Biotechnology)
Baek Nam-In (Graduate School of Biotechnology & Plant Metabolism Research Center, Kyunghee University)
Kim Sung-Hoon (Graduate School of East-West Medical Science, Kyunghee University)
Kim Dae-Keun (College of Pharmacy, Woosuk University)
Publication Information
Archives of Pharmacal Research / v.29, no.3, 2006 , pp. 191-194 More about this Journal
Abstract
Twigs from llex macropoda were extracted with MeOH, and the concentrated extracts were partitioned with $CH_2Cl_2$, EtOAc, n-BuOH, and $H_2O$. Repeated column chromatography of the $CH_2Cl_2$ fraction ultimately resulted in the isolation of two compounds, via activity-guided fractionation, using ACAT inhibitory activity measurements. According to the physico-chemical data, the chemical structures of these isolated compounds were identified as lupeol (1) and betulin (2). Compounds 1 and 2 were shown to inhibit the activity of hACAT-1 and hACAT-2 in a dose-dependent manner, and compounds 1 and 2 inhibited hACAT-1 with $IC_{50}$ values of 48 and $83{\mu}M$, respectively.
Keywords
llex macropoda; ACAT inhibitory activity; Lupeol; Betulin;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 1  (Related Records In Web of Science)
Times Cited By SCOPUS : 2
연도 인용수 순위
1 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)   DOI   ScienceOn
2 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)   DOI   ScienceOn
3 Roth, B. D., Blankley, J., and Hoefle, M. L., Inhibitors of acyl- CoA:cholesterol acyltransferase. 1. Identification and structureactivity relationships of a novel series of fatty acid anillide hypocholesterolemic agents. J. Med. Chem., 35, 1609-1617 (1992)   DOI
4 Leon, C., Hill, J. S., and Wasan, K. M., Potential role of acylcoenzyme A: cholesterol transferase (ACAT) inhibitors as hypolipidemic and antiatherosclerosis drugs. Pharm Res., 10, 1578-1588 (2005)
5 Goodman, D. S., Deykin, D., and Shiratori, T., The formation of cholesterol esters with rat liver enzymes. J. Biol. Chem., 239, 1335-1345 (1964)
6 Ahmad, V. U. and Atta-ur-Rahman., Handbook of natural products data: pentacyclic triterpenoids. Vol. 2. Elsevier, New York, pp. 1038-1039, (1994)
7 Patra, A., Chaudhuri, S. K., and Panda, S. K., Betulin-3-caffeate from Quercus suber. $^{13}C-NMR$ spectra of some lupenes. J. Nat. Prod., 51, 217-220 (1988)   DOI
8 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)   DOI
9 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)   DOI   ScienceOn
10 Siddiqui, S., Hafeez, F., Begum, S., and Siddiqui, B. S., Oleanderol, a new pentacyclic triterpene from the leaves of Nerium oleander. J. Nat. Prod., 51, 229-233 (1988)   DOI
11 Kim, D. H., Jung, S. J., Chung, I-S., Lee, Y-Y., Kim, D. K., Kim, S., H., Kwon, B-M., Jeong, T-S., Park, M-H., Seoung, N-S., and Baek, N-I., Ergosterol peroxide from flowers of Erigeron annuus L. as an anti-atherosclerosis agent. Arch. Pharm. Res., 28, 541-545 (2005)   과학기술학회마을   DOI
12 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 flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP- 1 in high cholesterol-fed rabbits. Biochem. Biophys. Res. Commun., 284, 681-688 (2001)   DOI   ScienceOn
13 Brown, M. S., Dana, S. E., and Goldstein, J. L., Cholesterol ester formation in cultured human fibroblasts. J. Biol. Chem., 250, 4025-4027 (1975)
14 Jeong, T. S., Kim, J. R., Kim, K. S., Cho, K. H., Bae, K. H., and Lee, W. S., Inhibitory effects of multi-substituted benzylidenzethiazolidine- 2,4-diones on LDL oxidation. Bioorg. Med. Chem., 12, 4017-4023 (2004)   DOI   ScienceOn
15 Ito, K. and Lai, J., Studies on the constituents of Marsdenia formosana Masamune. I. Isolation of tirterpenoids and structure of marsformal. Yakugaku Zasshi, 98, 249-256 (1978)   DOI
16 Joyce, C. W., Sheiness, G. S., Davis, M. A., Lee, R. G., Skinner, K., Anderson, R. A., and 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)   DOI