YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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Screening of Cyclooxygenase-2 (COX-2) Inhibitors from Natural Products

천연물로부터 사이클로옥시게나제-2 저해제 검색

  • Published : 1998.04.01
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Abstract

Tissue distributions and association of cyclooxygenase-2 (COX-2) with inflammatory have led us to search for COX-2 selective inhibitors from natural products. Conceptually, COX- 2 selective inhibitors should be expected to retain anti-inflammatory efficacy by inhibition of PGs production while reducing or eliminating the gastric, renal and hemostatic side effects commonly associated with NSAIDs use. Thus, a logical approach to the treatment of inflammatory diseases should involve the inhibitors of COX-2. To develop new COX-2 inhibitors from natural products, two hundred crude drugs were screened by inhibiting PGD2 generation in bone marrow derived mast cells (BMMC). Among them, 6 methanol extracts of crude drugs such as, Bletillae rhizoma, Aconiti kgreani rhizoma, Belamcandae rhizoma, Nelumbinis semen, Gleniae radix, Aurantii immatri pericarpium inhibited more than 85% of BMMC COX-2 activity at a concentration 2.5${\mu}$g/ml.

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References

  1. Cell v.83 Yes, but do they still headaches DeWitt, D.;W.L. Smith
  2. J. Biol. Chem. v.262 Biological and immunological characterization of rat spleen prostaglandin D synthase Urade, Y.;Fujimoto, N.;Ujihara, M.;Hayaishi, O.
  3. J. Immunol. v.143 The major source of endogenous prostaglandin D2 production is likely antigen-presenting cells-localization of glutathione-requiring prostaglandin-D synthase in histiocytes, dendritic and kupffer cells in various rat-tissues Urade, Y.;Ujihara, M.;Horiguchi, Y.;Ikai, K.;Hayaishi, O.
  4. Proc. Natl. Acad. Sci. USA v.88 Expression of a moitogen-responsive gene encoding prostaglandin synthase is regulated by messenger RNA splicing Xie, W.;Chipman, J.G.;Robertson, L.L.;Erikson, R.L.;Simmons, D.L.
  5. J. Biol. Chem. v.267 Structure of the mitogen-inducible Tis 10 gene and demonstratin that the Tis10-encoded protein is a functional prostaglandin G/H synthase Fletcher, B.S.;Kujubu, D.A.;Perrin, D.M.;HerschMan, H.R.
  6. J. Biol. Chem. v.268 Molecular cloning of human prostaglandin endoperoxide synthase type-Ⅱ and demonstration of expression in response to cytokines Jones, D.A.;Cartton, D.P.;Mclntyre, T.M.;Zimmerman, G.A.;Prescott, S.M.
  7. J. Biol. Chem. v.269 The orientation of prostaglandin endoperoxide synthase-1 and synthase-2 in the endoplasmic reticulum Otto, J.C.;Smith, W.L.
  8. J. Biol. Chem. v.270 Different intracellular location for prostaglandin H synthase-1 and synthase-2 Morita, I.;Schindler, M.;Regier, M.K.;Otto, J.C.;Hori, T.;DeWitt, D.L.;Smith, W.L.
  9. Proc. Natl. Acad. Sci. USA v.85 Primary structure of proistaglandin-G/H synthase from sheep vascular gland determined from the complementary-DNA sequence DeWitt, D.L.;Smith, W.L.
  10. J. Biol. Chem. v.263 Isolation and characterization of the complementary-DNA for sheep seminal-vesicle prostaglandin endoperoxide synthasee (cyclooxygenase) Merlie, J.P.;Ragan, D.;Mudd, J.;Needleman, P.
  11. FASEB. J. v.5 Human platelet erythroleukemia cell prostaglandin G/H synthase-cDNA cloning expression and gene chromosomal assignment Funk, C.D.;Funk, L.B.;Kennedy, M.E.;Pong, A.S.;Fitzgerald, G.A.
  12. Arch. Biochem. Biophys v.293 Prostaglandin endoperoxide synthase gene structure-identification of the transcriptional start site and 5'-flanking regulatory sequences Kraemer, S.A.;Meadde, E.A.;DeWitt, D.L.
  13. J. Biol. Chem. v.268 Differential regulation of inducible and constitutive prostaglandin endoperoxide synthase in osteoblastic Mc 3T3-E1 cells Pilbram, C.C.;Kawaguchi, H.;Hakeda, Y.;Voznesensky, O.;Alander, C.B.;Raisz, L.G.
  14. J. Biol. Chem. v.269 Induction of cyclooxygenase-2 in rat vascular smooth-muscle cells in vitro and in-vivo Pritchard, K.A.;O'Banion, M.K.;Miano, J.M.;Vlasic, N.;Bhatia, U.G.;Young, D.A.;Stemerman, M.b.
  15. J. Biol. Chem. v.269 Ligand induced prostaglandin synthesis requires expression of the Tis10/Pgs-2 prostaglandin synthase gene in murine fibroblast and macrophages Reddy, S.T.;Herschman, H.R.
  16. J. Biol. Chem. v.269 Endothelin stimulates prostaglandin endoperoxide synthase-2 messenger-RNA expression and protein-synthesis through a tyrosine kinase signaling pathway in rat mesangial cells Kester, M.;Coroneos, E.;Thimas, P.J.;Dunn, M.J.
  17. J. Immunol. v.155 IgE-dependent activation of cytokine-primed mouse cultured mast cells induces a delayed phase of prostaglandin $D_2$ generation via prostaglandin endoperoxidase synthase-2 Murakami, M.;Bingham, C.O.;Matsumoto, R.;Austen, K.F.;Arm, J.P.
  18. J. Biological Chem. v.270 c-Kit ligand mediates increased expression of cytsolic phopholipase $A_2$, prostaglandin endoperoxide synthase-1, and gematopoietic prostaglandin $D_2$ synthesis and increased IgE-dependent prostaglandin $D_2$ in immature mouse mast cells Murakami, M.;Matsumoto, R.;Urade, Y.;Austen, K.F.;Arm, J.P.
  19. J. Biol. Chem. v.269 Acetylation of human prostaglandin endoperoxide synthase-2(cyclooxygenase-2) by aspirin Lecomte, M.;Kaneuville, O.;Ji, C.;DeWitt, D.L.;Smith, W.L.
  20. Nature v.367 Pharmacology-towards a better aspirin Vane, J.
  21. Prostaglandins v.31 Time dependent inhibition of platelet cyclo-oxygenase by indomethacin is slowly reversible Walenga, R.W.;Wall, S.F.;Setty, B.N.;Stuart, M.J.
  22. J. Biol. Chem. v.268 Different inhibition of prostaglandin endoperoxide synthse(cyclooxygenase) isozymes by aspirin and other non-steroidal antiinflammatory drugs Meade, E.A.;Smith, W.L.;De Witt, D.L.
  23. VEAOL v.47 NS-398, a new antiinflammatory agent, selectively inhibits prostaglandin G/H synthase cyclooxygenase02(COX-2) activity in-vitro Futaki, N.;Takahashi, S.;Yokoyama, M.;Arai, I.;Higuchi, S.;Otomo, S.
  24. Proc. Natl. Acad. Sci. USA v.91 Selective-inhibition of inducible cyclooxygenase-2 in-vivo is antiinflammatory and nonulcerogenic Masferrer, J.L.;Zweifel, B.S.;Manning, P.T.;Hauser, S.D.;Leahy, K.M.;Smith, W.G.;Leakson, P.C.;Seibert, K.