Inhibition of Leukotriene Biosynthesis by Quinolone Alkaloids from the Fruits of Evodia rutaecarpa

Abstract

The n-hexane extract of the fruits of Evodia rutaecarpa showed a considerable inhibiting effect on leukotriene biosynthesis in human granulocytes. Bioassay-guided fractionation of the extract led to the isolation of the 5 quinolone alkaloids: 1-methyl-2-nonyl-4(1H)-quinolinone, 1-methyl-2-(6Z)-6-undecenyl-4(1H)-quinolinone, 1-methyl-2-(4Z,7Z)-4,7-tridecadienyl-4(1H)-quinolinone, evocarpine and 1-methyl-2-(6Z,9Z)-6,9-pentadecadienyl-4(1H)-quinolinone. The compounds exhibited inhibitory activity on leukotriene biosynthesis in a bioassay using human polymorphonuclear granulocytes, with IC₅₀ values of 12.1, 10.0, 10.1, 14,6 and 12.3 μM, respectively. Structure elucidation of the compounds was achieved by 1D and 2D NMR experiments and comparison of spectral data with literature data.

Key words

Evodia rutaecarpa - Rutaceae - leukotriene biosynthesis - quinolone alkaloids - traditional Chinese medicine (TCM)

References

• 1 Samuelsson B, Funk C D. Enzymes involved in the biosynthesis of leukotriene B4.  J Biol Chem. 1989;  264 19 469-72
• 2 Werz O. 5-Lipoxygenase: Cellular biology and molecular pharmacology.  Curr Drug Targets - Inflamm Allergy. 2002;  1 23-44
• 3 Bauer R. Cyclooxygenase and 5-lipoxygenase as targets of medicinal plant research.  In: Bioassay Methods in Natural Product and Drug Development. (Eds.: Bohlin, Bruhn JC) Kluwer Academic Publishers Dortrecht, Boston, London; 1999: 119-141
• 4 Pharmacopoeia of the People’s Republic of C hina. (English Edition). Chemical Industry Press Beijing, China; 2000: p 73
• 5 Seebacher W, Simic N, Weis R, Saf R, Kunert O. Complete assignments of ¹H and ¹³C NMR resonances of oleanic acid, 18α-oleanic acid, ursolic acid and their 11-oxo derivatives.  Magn Reson Chem. 2003;  41 636-8
• 6 Tang Y Q, Feng X Z, Huang L. Quinolone alkaloids from Evodia rutaecarpa .  Phytochemistry. 1996;  43 719-22
• 7 Sugimoto T, Miyase T, Kuroyanagi M, Ueno A. Limonoids and quinoline alkaloids from Evodia rutaecarpa Bentham.  Chem Pharm Bull. 1988;  36 4453-61
• 8 Oliva A, Meepagala K M, Wedge D E, Harries D, Hale A L, Aliotta G, Duke S O. Natural fungicides from Ruta graveolens L. leaves, including a new quinolinone alkaloid.  J Agr Food Chem. 2003;  51 890-6
• 9 Zalibera L, Milata V, Ilavsky D. ¹H and ¹³C NMR spectra of 3-substituted 4- quinolinones.  Magn Reson Chem. 1998;  36 681-4
• 10 Finney J D. Statistical Methods in Biological Assay. Charles Griffin London; 1978: pp 58-65
• 11 Moon T C, Murakami M, Kudo I, Son K H, Kim H P, Kang S S, Chang H W. A new class of COX-2 inhibitor, rutaecarpine from Evodia rutaecarpa .  Inflamm Res. 1999;  48 621-5
• 12 Sheu J R, Hung W C, Wu C H, Lee Y M, Yen M H. Antithrombotic effect of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, on platelet plug formation in in vivo experiments.  Brit J Haematol. 2000;  110 110-5
• 13 Sheu J R, Kan Y C, Hung W C. The antiplatelet activity of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, is mediated through inhibition of phospholipase C.  Thromb Res. 1998;  92 53-64
• 14 Hu C P, Xiao L, Deng H W, Li Y J. The cardioprotection of rutaecarpine is mediated by endogenous calcitonin related gene peptide through activation of vanilloid receptors in guinea-pig hearts.  Planta Med. 2002;  68 705-9
• 15 Kobayashi Y, Nakano Y, Hoshikuma K, Yokoo Y oshiharu, Kamiya T. The bronchioconstrictive action of evodiamine, an indoloquinazoline alkaloid isolated from the fruits of Evodia rutaecarpa, on guinea-pig isolated bronchus: Possible involvement of vanilloid receptors.  Planta Medica. 2000;  66 526-30
• 16 Lee H S, Oh W K, Choi H C, Lee J W, Kang D O, Park C S, Mheen T I, Ahn J S. Inhibition of angiotensin II receptor binding by quinolone alkaloids from Evodia rutaecarpa .  Phytother Res. 1998;  12 212-4
• 17 Jeong S K, Rho M C, Chung M Y, Song H Y, Kang J S, Kim K, Lee H S, Kim J K. Quinoline alkaloids, diacylglyceryl acyltransferase inhibitors from the fruits of Evodia rutaecarpa .  Planta Med. 2002;  68 1131-3
• 18 Rho T C, Bae E A, Kim D H, Oh W K, Kim B Y, Ahn J S, Lee H S. Anti-Helicobacter pyleri activity of quinolone alkaloids from Fructus Evodiae.  Biol Pharm Bull. 1999;  22 1141-3
• 19 Kim Y C, Kim N Y, Jeong S J, Sohn D H, Miyamoto T, Higuchi R. Biologically active chinolone alkaloids from Evodia rutaecarpa on Artemia salina .  Planta Med. 1998;  64 490
• 20 Yamahara J, Kobayashi G, Matsuda H, Fujimura H. The vasorelaxant effect of evocarpine in isolated aortic strips: mode of action.  Eur J Pharmacol. 1988;  155 139-43
• 21 Kano Y, Chen X F, Kanemaki S, Zong Q, Komatso K. Pharmakokinetics of a galenic preparation. XV. Pharmacokinetics study of evocarpine and its metabolites in rats.  Chem Pharm Bull. 1991;  39 3064-6
• 22 Chuang W C, Cheng C M, Chang H C, Chen Y P, Sheu S J. Contents of constituents in mature and immature fruits of Evodia species.  Planta Med. 1999;  65 567-71