Korean Journal of Pharmacognosy (생약학회지)

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지

Inhibitory Effects of Natural Plant Extracts on Lipoprotein-Associated Phospholipase $A_2$, Platelet-Activating Factor Acetylhydrolase

자생식물 추출물의 Lipoprotein-Associated Phospholipase $A_2$, Platelet-Activating Factor Acetylhydrolase 저해활성

  • Yu, Ha-Na (Lipid Metabolism Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Kyung-Hyun (Lipid Metabolism Research Laboratory Korea Research Institute of Bioscience and Biotechnology) ;
  • Sok, Dai-Eun (College of Pharmacy, Chungnam National University) ;
  • Jeong, Tae-Sook (Lipid Metabolism Research Laboratory Korea Research Institute of Bioscience and Biotechnology)
  • 유하나 (한국생명공학연구원 지질대사연구실) ;
  • 조경현 (한국생명공학연구원 지질대사연구실) ;
  • 석대은 (충남대학교 약학대학) ;
  • 정태숙 (한국생명공학연구원 지질대사연구실)
  • Published : 2003.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

The regulation of plasma lipid level, particularly LDL cholesterol, represents the focus of current therapy for atherosclerosis. And $Lp-PLA_2$ is able to hydrolyse oxidized phosphatidylcholine within LDL into lyso-PC and oxidized fatty acids. $Lp-PLA_2$ is a potential biomarker of coronary heart disease and plays an important proinflammatory role in the progression of atherosclerosis. We investigated the inhibitory effects of methanol extracts of 224 natural plants on $Lp-PLA_2$ activity. Seven kinds of methanol extracts of tested plants showed above 50% inhibitory effect with the concentration of $100\;{\mu}g/ml$. The concentrated aqueous suspensions of each methanol extract were partitioned with n-hexane, $CHCl_3$, and EtOAc. Among them, EtOAc extracts of Astilbe chinensis var. davidii (root) and Pourthiaea villosa var. brunnea (leaf) significantly inhibited $Lp-PLA_2$ activity at the same concentration.

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$A_2$ in vascular disease. (2001) Circ. Res. 89: 298-304 https://doi.org/10.1161/hh1601.095598
  5. Paramo, J. A., Beloqui, O. and Diez, J. (2001) Atherosclerosis: Is it time for a new name? Circulation 104: e38 https://doi.org/10.1161/01.CIR.104.7.e38
  6. James, S., Stuart, M. C., Ian, E, Christopher, G. I., Peter, W.M. and James, H. M. (1995) Prevention of coronary heart disease with prevention in men with hypercholesterolemia N. Engl. J. Med. 333: 1301-1307 https://doi.org/10.1056/NEJM199511163332001
  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 $A_2$ as independent predictor of coronary heart disease. N. Engl. J. Med. 343: 1148-1155 https://doi.org/10.1056/NEJM200010193431603
  8. Dada, N., Kim, N. W.and Wolfert, R. L. (2002) $Lp-PLA_2$: an emerging biomarker of coronary heart disease. Expert Rev. Mol. Diagn. 2: 17-22 https://doi.org/10.1586/14737159.2.1.17
  9. Tew, D. G., Southan, C., Rice, S. Q., Lawrence, M. P., Li, H., Boyd, H. E, Moores, K, Gloger, I. S. and Macphee, C. H. (1996) Purification, properties, sequencing, and cloning of a lipoprotein associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins. Arterioscler. Thromb. Vase. BioI. 16: 591-599 https://doi.org/10.1161/01.ATV.16.4.591
  10. Macphee, C. H. (2001) Lipoprotein-associated phospholipase $A_2$: a potential new risk factor for coronary artery disease and a therapeutic target. Curr. Opin. Pharmacol. 1: 121-125 https://doi.org/10.1016/S1471-4892(01)00024-8
  11. Asano, K., Okamoto, S., Fukunaga, K, Shiomi, T, Mori, T, Iwata, M., Ikeda, Y. and Yamaguchi, K (1999) Cellular source(s) of platelet-activating-factor acethylhydrolase activity in plasma. Biochem. Biophys. Res. Commun. 261: 511-514 https://doi.org/10.1006/bbrc.1999.1066
  12. 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
  13. 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., Tew, D. G. and Hickey, D. M. (1999) Lipoprotein-associated phospholipase $A_2,$ platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor. Biochem. J. 338: 479-487 https://doi.org/10.1042/0264-6021:3380479
  14. Hakkinen, T.,Luoma, J. S., Hiltunen, M. O., Macphee, C. H., Milliner, K J., Patel, L., Rice, S. Q., Tew, D. G., Karkola, K. and Yla-Herttuala, S. (1999) Lipoprotein-associated $PLA_2,$ platelet-activating factor acetylhydrolase is expressed by macrophage in human and atherosclerotic lesion. Arterioscl. Thromb. Vase. BioI. 19: 2909-2917 https://doi.org/10.1161/01.ATV.19.12.2909
  15. Benson, G. M., Grimsditch. D., Milliner, K, Moores, K., Body, H., Tew, D., Hickey, D., Ife, R., Suckling, K, Macphee, C. (2000) Anti-atherosclerotic effect of SB-244323, a lipoprotein associated phospholipase $A_2$ inhibitor, in WHHL rabbits. Atherosclerosis 151: 166
  16. Suckling, E. S. and Macphee, C. H. (2002) Lipoprotein associated phospholipase $A_2$: a tagget directed at the atheroslcerotic plaque. Expert Opin. Ther. Targets 6: 309413 https://doi.org/10.1517/14728222.6.3.309
  17. Boyd, H. F, Fell, S. C. M., Flynn, S. T., Hickey, D. M. B., Ife, R. J., Leach, C. A, Macphee, C. H., Milliner, K. J., Moores, K E., Pinto, I. L., et al. (2000) N-l substituted pyrimidine-4-ones: novel, orally active inhibitors of lipoprotein-associated phospholipase $A_2$ Bioorg. Med. Chern. Lett. 10: 2557-2561 https://doi.org/10.1016/S0960-894X(00)00510-2
  18. Bligh E. G. and Dyer, W. J. (1959) A rapid method of total lipid extraction and purification. Can. J. Biochem. Physiol. 37: 912-917
  19. Caslake, M. J., Parkard, C. J., Suckling, K. E., Holmes, S. D., Chamberlain, R. and Macphee, C. H. (2000) Lipoproteinassociated phospholipase $A_2,$ platelet-activating factor acethylhydrolase: a potential new risk factor for coronary artery disease. Atherosclerosis 150: 413-419 https://doi.org/10.1016/S0021-9150(99)00406-2
  20. Thirkettle, J., Alvarez, E, Boyd, H., Brown, M., Diez, E., Hueso, J., Elson, S., Fulston, M., Gershater, C., Morata, M. L., et al. (2000) SB-253514 and analogues; novel inhibitors of lipoprotein-associated phospholipase $A_2$ produced by Pseudomonas fluorescens DSM 11579. I. Fermentation of producing strain, isolation and biological activity. J. Antibiot. 53: 664-669 https://doi.org/10.7164/antibiotics.53.664
  21. Busby, D. J., Copley, R. C., Hueso, J. A., Readshaw, S. A and Rivera, A (2000) SB-253514 and analogues: novel inhibitors of lipoprotein-associated phospholipase $A_2$ produced by Pseudomonas jluorescens DSM 11579. II. Physicochemical properties and structure elucidation. J. Antibiot. 53: 670-676 https://doi.org/10.7164/antibiotics.53.670
  22. Thirkettle, J. (2000) SB-253514 and analogues; novel inhibitors of lipoprotein-associated phospholipase $A_2$ produced by Pseudomonas jluorescens DSM 11579. III. Biotransformation using naringinase. J. Antibiot. 53: 733-735 https://doi.org/10.7164/antibiotics.53.733
  23. Blackie, J. A, Bloomer, J. C, Brown, M. J., Cheng, H. Y, Elliott, R. L., Hammond, B., Hickey, D. M., Ife, R. J., Leach, C. A, Lewis, V. A, et al. (2002) The discovery of SB435495. A potent, orally active inhibitor of lipoproteinassociated phospholipase $A_2$ for evaluation in man. Bioorg. Med. Chem. Lett. 12: 2603-2606 https://doi.org/10.1016/S0960-894X(02)00473-0