Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
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Screening of Anti-atherogenic Substances from Insect Resources

곤충자원으로부터 항동맥경화 활성물질 탐색

  • Park, Doo-Sang (Insect Resources Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Yoon, Mi-Ae (Insect Resources Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Xu, Ming-Zhe (Insect Resources Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Yu, Ha-Na (Lipid Metabolism Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Ju-Ryoung (Lipid Metabolism Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jeong, Tae-Sook (Lipid Metabolism Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Ho-Yong (Insect Resources Laboratory, Korea Research Institute of Bioscience and Biotechnology)
  • 박두상 (한국생명공학연구원 곤충자원연구실) ;
  • 윤미애 (한국생명공학연구원 곤충자원연구실) ;
  • 서명철 (한국생명공학연구원 곤충자원연구실) ;
  • 유하나 (한국생명공학연구원 지질대사연구실) ;
  • 김주령 (한국생명공학연구원 지질대사연구실) ;
  • 정태숙 (한국생명공학연구원 지질대사연구실) ;
  • 박호용 (한국생명공학연구원 곤충자원연구실)
  • Published : 2004.09.30
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Abstract

Lipoprotein-associated phospholipase $A_2\;(Lp-PLA_2)$ is a potential biomarker of coronary heart disease and plays an important proinflammatory role in the progression of atherosclerosis. Also acyl-CoA: cholesterol acyltransferase (ACAT) and oxidized low-density lipoprotein (LDL) playa key role in atherosclerosis, respectively. And so, the inhibitory activities of the methanol extracts of 42 insect resources were examined on $Lp-PLA_2$, ACAT, and LDL oxidation for screening of anti-atherogenic substances. Among them, the methanol extracts of Eurydema rugosa significantly inhibited all of upper three activities. Several kinds of tested insects having high inhibitory effect with the methanol extracts were extracted with n-hexane, ethyl acetate, and acetone, and their inhibitory activities were tested.

Keywords

References

  1. Glass, C. K. and Witztum, J. L. (2001) Atherosclerosis: The road ahead. Cell 104: 503-516 https://doi.org/10.1016/S0092-8674(01)00238-0
  2. Lusis, A. J. (2000) Atherosclerosis. Nature 407: 233-241 https://doi.org/10.1038/35025203
  3. Ross, R. (1999) Atherosclerosis-an inflammatory disease. N. Engl. J. Med. 340: 233-241
  4. Hurt-Camejo, E., Camejo, G., Peilot, H., Oomi, K., and Kovanen, P. Phospholipase $A_2$ in vascular disease. (2001) Circ. Res. 89: 298-304 https://doi.org/10.1161/hh1601.095598
  5. Bays, H. and Stein, E. A. Pharmacotherapy for dyslipidemia - current therapies and future agents. (2003) Expert Opin. Pharmacother. 4: 1901-1938 https://doi.org/10.1517/14656566.4.11.1901
  6. Prescott, S. M., Zimmerman, G. A, Stafforini, D. M., and Mcintyre, T. M. (2000) Platelet activating factor and related lipid mediators. Ann. Rev.' Biochem. 69: 419-445 https://doi.org/10.1146/annurev.biochem.69.1.419
  7. Packard, C. J., O'Reilly, S. J., Caslake, M. J., McMahon, A. D., Ford, I., Cooney, J., Macphee, C. H., Suckling, K E., Krishna, M., Wilkinson, F. E., Rumley, A. and Lowe. G. D. O. (2000) Lipoprotein associated phospholipase A2 asindependent predictor of coronarY heart disease. N. Engl. 1. Med. 343: 1148-1155 https://doi.org/10.1056/NEJM200010193431603
  8. MacPhee, C. H., Moores, K. E., Boyd, H. F., Dhanak, D., Ife, R. J., Leach, C. A, Leake, D. S., Milliner, K. J., Patterson, R. A, Suckling, K. E., 'few, D. G., and Hickey, D. M. (1999) Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor. J. Biochem. 338: 479-487 https://doi.org/10.1042/0264-6021:3380479
  9. Macphee, C. H. (2001) Lipoprotein-associated phospholipase $A_2$: a potential new risk factor for coronary qrtery disease and a therapeutic target. Curro Opin. Pharmacol. 1: 121: a potential new risk factor for coronary qrtery disease and a therapeutic target. Curro Opin. Pharmacol. 1: 121-125 https://doi.org/10.1016/S1471-4892(01)00024-8
  10. Suckling, E. S. and Macphee, C. H. (2002) Lipoproteinassociated phospholipase $A_2$: a tagget directed at the atheroslcerotic plaque. Expert Opin. Ther. Targets 6: 309-413 https://doi.org/10.1517/14728222.6.3.309
  11. Chang, T. Y., Chang, C. C. Y., and Cheng, D. (1997) Acylcoenzyme A : cholesterol acyltransferase. Annu. Rev. Biochem. 66: 613-638 https://doi.org/10.1146/annurev.biochem.66.1.613
  12. Rudel, L. L. (2001) Acyl coenzyme A:cholesterol acyltransferade type 1 and 2 : structure and function in atherosclerosis. Curro opin. lipidol. 12: 121-127 https://doi.org/10.1097/00041433-200104000-00005
  13. Accad, M., Smith S. J., Newland, D. L., Sanan, D. A, King, L. E. Jr, Linton, M. F, Fazio, S., and Farese, R. V. Jr. (2000) Massive xanthomatosis and altered composition of atherosclerotic lesions in hyperlipidemic mice lacking acyl CoA:cholesterol acyltransferase 1. J. Clin. Invest. 105: 711-719 https://doi.org/10.1172/JCI9021
  14. Buhman, K. K., Accad, M., Novak, S., Choi, R. S., Wong, J. S., Hamilton, R. L., Turley, S., and Farese, R. V. Jr. (2000) Resistance to diet-induced hypercholesterolemia and gallstone formation in ACAT2-deficient mice. Nautre Med. 6: 1341-1347 https://doi.org/10.1038/82153
  15. Steinberg, D.; Parthasarathy, S.; Carew, T. E.; Khoo, J. C.; Witztum, J. L. (1989) Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N. Engl. J. Med. 1989, 320, 915-924 https://doi.org/10.1056/NEJM198904063201407
  16. Jessup, W. and Kritharides L. (2000) Metabolism of oxidized LDL by macrophages. Curro Opin. lipidol., 11: 473-481 https://doi.org/10.1097/00041433-200010000-00005
  17. Bjorkhem, I., Henriksson-Freyschuss, A, Breuer, O., Diczfalusy, U. Berglund, L., and Henriksson, P. (1991) The antioxidant butylated hydroxytoluene protects against atherosclerosis. Arterioscler. Thromb. 11: 15-22 https://doi.org/10.1161/01.ATV.11.1.15
  18. Erickson, S. K., Shrewsbury, M. A, Brooks, C., and Meyer, D. J. (1980) Rat liver acyl coemzyme A:cholesterol acyltransferase: its regulation in vivo and some of its properties in vitro. J. Lipid Res. 21: 930-941
  19. Bradford, M. M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72: 248254 https://doi.org/10.1016/0003-2697(76)90527-3
  20. Brecher, P. and Chan, C. (1980) Properties of Acyl-CoA : Chdlesteml acyltransflitase in aortic rrlittosomcs froth atherosclerotic rabbit. Biochim. Biophys. Acta 617: 458-471 https://doi.org/10.1016/0005-2760(80)90012-0
  21. Jeong, T. S., Kim, S. U., Son, K. H., Kwon, B. M., Kim, Y. K., Choi, M. D., a,nd Bok, S. H. (1995) GERI-BPOOI compounds, new inhibitors of Acyl-CoA:cholesterol acyltransferase from Aspergillus fumigatus F37. I. Production, isolation, and physico-chemical and biological properties. J. Antibiotics 48: 751-756 https://doi.org/10.7164/antibiotics.48.751
  22. Cho, K H., An, S. J., Lee, W. S., Paik, Y. K, Kim, Y. K., and Jeong. T. S. (2003) ;Mass-production of human ACAT-l and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation. Biochem. Biophysic. Res. Comm. 309: 864-872 https://doi.org/10.1016/j.bbrc.2003.08.077
  23. Havel, R. J., Edger, H. A, and Bradgon, J. H. (1955) The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest. 34: 1345-1353 https://doi.org/10.1172/JCI103182
  24. Boyd, H. F, Fell, S. C. M., Flynn, S. T., Hickey, D. M. B., life, R. J., Leach, C. A, Macphee, C. H., Milliner, K J., Moores, K. E., Pinto, I. L. (2002) N-l substituted pyrimidine-4-ones: novel, orally active inhibitors of lipoprotein-associated phospholipase $A_2$Bioorg. Med. Chem. Lett., 10: 2557-2561 https://doi.org/10.1016/S0960-894X(00)00510-2
  25. Yu, H. N., Sok, D. E., and Jeong, T. S. (2003) Inhibitory effects of natural plant extracts on lipoprotein-associated phospholipase Az inhibitor. Kor. J. Pharmacogn. 34: 100-108
  26. Bloomer, J. C., Boyd, H. F, Hickey, D. M. B., Ife, R. J., Leach, C. A, Macphee, C. H., Miller, K J., Pinto, I. L., Rawlings, D. A, Smith, S. A., et al. (2001) 1-(arylpiperazinylarnidoalkyl)-pyrimidones: orally active inhibitors of lipoprotein-assiciated phospholipase $A_2$. Bioorg. Med. Chem. Lett., 11:1925-1929 https://doi.org/10.1016/S0960-894X(01)00346-8
  27. Ahn, B. T., Lee, S., Lee, S. B., Lee, E. S., Kim, J. G., Bok, S. H., and Jeong, T. S. (2001) Low-density lipoprotein-antioxidant constituents of Saururus chinensis. J. Nat. Prod. 64: 1562-1564 https://doi.org/10.1021/np0006061
  28. Xu, M.-Z., Lee, W. S., Kim, M. J., Park, D.-S., Yu, H., Tian, G.-R., Jeong, T.-S., and Park, H.-Y. (2004) Acyl-CoA: cholesterol acyltransferase inhibitory activities of fatty acid arnides isolated from Mylabris phalerate Pallas Bioorg. Med. Chem. Lett., 14: 4277-4280 https://doi.org/10.1016/j.bmcl.2004.05.086