Lipids

, Volume 40, Issue 11, pp 1171–1177 | Cite as

Inhibition of 12- and 15-lipoxygenase activities and protection of human and tilapia low density lipoprotein oxidation by I-Tiao-Gung (Glycine tomentella)

Articles

Abstract

I-Tiao-Gung, Glycine tomentella, has been used extensively as a traditional herbal medicine to relieve physical pain, but its bioactivity has not been studied systematically. Ninety-five percent ethanol extracts of G. tomentella (GT-E) showed antioxidant activity in human plasma by prolonging the lag phase (+Tlag) of Cu2+-induced, LDL oxidation and were dose dependent. The+Tlag of LDL combined with 3.2 μg/mL GT-E was similar to that with 2.0 μM (ca. 0.5 μg/mL) Trolox. A similar inhibitory effect was found toward tilapia plasma LDL. In addition, GT-E inhibited tilapia thrombocyte (nucleated platelet), 5-, 12-, and 15-lipoxygenase (LOX). The IC50 values were 0.43, 0.72, and 0.42 μg/mL, respectively, whereas the IC50 values for nordihydroguaiaretic acid (NDGA) on 5-, 12-, and 15-LOX were 2.3, 1.6, and 1.7 μg/mL, respectively. The IC50 value for cyclooxygenase-2 (COX-2) inhibition by GT-E was 42.0 μg/mL, whereas the IC50 value by indomethacin as a positive control was 0.61 μg/mL. The prevention of LDL oxidation and the dual inhibition of LOX and COX-2 are indicative of the possible roles of I-Tiao-Gung in antiatherosclerosis and anti-inflammation.

Abbreviations

COX

cycloxygeanse

GT

Glycine tomentella Hayata

GTE

95% ethanol extracts of Glycine tomentella

hCOX-2

human recombinant COX-2

HETE

hydroxyl eicosatetraenoic acid

LOX

lipoxygenase

LTB4

leukotrine B4

NDGA

nordihydroguaiaretic acid

+Tlag

lag phase of LDL oxidation

Trolox

6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ross, R. (1999) Atherosclerosis: An Inflammatory Disease, N. Engl. J. Med. 340, 115–126.PubMedCrossRefGoogle Scholar
  2. 2.
    Steinberg, D. (1997) Low Density Lipoprotein Oxidation and Its Pathobiological Significance, J. Biol. Chem. 272, 20963–29066.PubMedCrossRefGoogle Scholar
  3. 3.
    Schumacher, M., Eber, B., Tatzber, F., Kaufmann, P., Esterbauer, H., and Klein, W. (1992) LDL Oxidation and Coronary Atherosclerosis, Lancet 16, 1183–1186.Google Scholar
  4. 4.
    Mertens, A., and Holvoet, P. (2001) Oxidized LDL and HDL: Antagonists in Atherothrombosis, FASEB J. 15, 2073–2084.PubMedCrossRefGoogle Scholar
  5. 5.
    Ross, R. (1993) The Pathogenesis of Atherosclerosis: A Perspective for 1990s, Nature 362, 801–809.PubMedCrossRefGoogle Scholar
  6. 6.
    Belkner, J., Stender, H., and Kuhn, H. (1998) The Rabbit 15-Lipoxygenase Preferentially Oxygenates LDL Cholesterol Esters, and This Reaction Does Not Require Vitamin E, J. Biol. Chem. 273, 23225–23232.PubMedCrossRefGoogle Scholar
  7. 7.
    Cyrus, T., Witztum, J.L., Rader, D.J., Tangirala, R., Fazio, S., Linton, M.F., and Funk, C.D. (1999) Disruption of the 12/15-Lipoxygenase Gene Diminishes Atherosclerosis in Apo E-Deficient Mice, J. Clin. Invest. 103, 1597–1604.PubMedCrossRefGoogle Scholar
  8. 8.
    Fujita, H., Saito, F., Sawada, T., Kushiro, T., Yagi, H., and Kanmatsuse, K. (1999) Lipoxygenase Inhibition Decreases Neointimal Formation Following Vascular Injury, Atherosclerosis 147, 69–75.PubMedCrossRefGoogle Scholar
  9. 9.
    Yamashita, H., Nakamura, A., Noguchi, N., Niki, E., and Kuhn, H. (1999) Oxidation of Low Density Lipoprotein and Plasma by 15-Lipoxygenase and Free Radicals, FEBS Lett. 445, 287–290.PubMedCrossRefGoogle Scholar
  10. 10.
    Harats, D., Shaish, A., George, J., Mulkins, M., Kurihara, H., Levkovitz, H., and Sigal, E. (2000) Overexpression of 15-Lipoxygenase in Vascular Endothelium Accelerates Early Atherosclerosis in LDL Receptor-Deficient Mice, Arterioscler, Thromb. Vasc. Biol. 20, 2100–2105.Google Scholar
  11. 11.
    Bocan, T.M., Rosebury, W.S., Mueller, S.B., Kuchera, S., Welch, K., Daugherty, A., and Cornicelli, J.A. (1998) A Specific 15-Lipoxygenase Inhibitor Limits the Progression and Monocyte-Macrophage Enrichment of Hypercholesterolemia-Induced Atherosclerosis in the Rabbit, Atherosclerosis 136, 203–216.PubMedCrossRefGoogle Scholar
  12. 12.
    Seibert, K., Zhang, Y., Leahy, K., Hauser, S., Masferrer, J., Perkins, W., Lee, L., and Isakson, P. (1994) Pharmacological and Biochemical Demonstration of the Role of Cyclooxygenase-2 in Inflammation and Pain, Proc. Natl. Acad. Sci. USA 91, 12013–12017.PubMedCrossRefGoogle Scholar
  13. 13.
    Harada, Y., Hatanaka, K., Kawamura, M., Saito, M., Ogino, M., Majima, M., Ohno, T., Yamamoto, K., Taketani, Y., Yamamoto, S., et al. (1996) Role of Prostaglandin H Synthase-2 in Prostaglandin E2 Formation in Rat Carrageenan-Induced Pleurisy, Prostaglandins 51, 19–33.PubMedCrossRefGoogle Scholar
  14. 14.
    Kurumbail, R.G., Stevens, A.M., Gierse, J.K., McDonald, J.J., Stegeman, R.A., Pak, J.Y., Gildehaus, D., Miyashiro, J.M., Penning, T.D., Seibert, K., et al. (1996) Structural Basis for Selective Inhibition of Cyclooxygenase-2 by Anti-Iinflammatory Agents, Nature 384, 644–648.PubMedCrossRefGoogle Scholar
  15. 15.
    Bertolini, A., Ottani, A., and Sandrini, M. (2001) Dual Acting Anti-inflammatory Drugs: A Reappraisal, Pharmacol. Res. 44, 437–450.PubMedCrossRefGoogle Scholar
  16. 16.
    Bonnet, C., Bertin, P., Trèves, R., and Rigaud, M. (1995) Lipoxygenase Products and Expression of 5-LOX and FLAP in Human Synovial Cells, Prostaglandins 50, 127–135.PubMedCrossRefGoogle Scholar
  17. 17.
    Sharon, P., and Stenson, W.F. (1984) Enhanced Synthesis of Leukotriene B-4 by Colonic Mucosa in Inflammatory Bowel Disease, Gastroenterology 86, 453–460.PubMedGoogle Scholar
  18. 18.
    Chisolm, G.M., and Steinberg, D. (2000) The Oxidation Modification Hypothesis of Atherogenesis: An Overview, Free Radic. Biol. Med. 28, 1815–1826.PubMedCrossRefGoogle Scholar
  19. 19.
    Chen, C.R. (1979) Dictionary of Chinese Medicine, p. 46, World Book, Taipei, Taiwan.Google Scholar
  20. 20.
    Ko, Y.J., Wu, Y.W., and Lin, W.C. (2004) Hypolipidemic Effect of Glycine tomentella Root Eextract in Hamsters, Am. J. Chin. Med. 32, 57–63.PubMedCrossRefGoogle Scholar
  21. 21.
    Pan, B.S., Kuo, Y.Y., Chen, T.S., and Liu, Y.C. (2005) Anti-oxidative and Anti-inflammatory Activities of Two Different Species of a Chinese Herb I-Tiao-Gung, Life Sci. 77, 2830–2839.CrossRefGoogle Scholar
  22. 22.
    Pan, B.S., Hsu, H.H., Chen, S., and Chen, H.M. (1999) Effects of α-Tocopherol on Lipoxygenase-Catalyzed Oxidation of Highly Unsaturated Fatty Acid, in Proceedings of the 3rd International Conference on Food Science & Technology, pp. 76–85. Institute of Food Technologists, Chicago.Google Scholar
  23. 23.
    Stokes, E.E., and Firkin, B.G. (1971) Studies of the Peripheral Blood of the Port Jackson Shark (Heterodontus portusjacksoni) with Particular Reference to the Thrombocyte, Br. J. Haematol. 20, 427–435.PubMedGoogle Scholar
  24. 24.
    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, 744–748.CrossRefGoogle Scholar
  25. 25.
    Berger, M., Schwarz, K., Thiele, H., Reimann, I., Huth, A., Sabine Borngraber, S., Kuhn, H., and Thiele, B.J. (1998) Simultaneous Expression of Leukocyte-Type 12-Lipoxygenase and Reticulocyte-Type 15-Lipoxygenase in Rabbits, J. Mol. Biol. 278, 935–948.PubMedCrossRefGoogle Scholar
  26. 26.
    Kleinveld, H.A., Hak-Lemmers, H.L.M., Stalenhoef, A.F.H., and Demacker, P.N.M. (1992) Improved Measurement of Low-Density-Lipoprotein Susceptibility to Copper-Induced Oxidation: Application of a Short Procedure for Isolating Low Density Liporptein, Clin. Chem. 38, 2066–2072.PubMedGoogle Scholar
  27. 27.
    Lloyd-Evans, P., Barrow, S.E., Hill, D.J., Bowden, L.A., Rainger, G.E., Knight, J., and Rowly, A.F. (1994) Eicosanoid Generation and Effects on the Aggregation of Thrombocytes from the Rainbow Trout, Oncorhynchus mykiss, Biochim. Biophys. Acta 1215, 291–299.PubMedGoogle Scholar
  28. 28.
    Kikugawa, K., Beppu, M., Sato, A., and Kasai, H. (1997) Separation of Multiple Yellow Fluorescent Lipofusin Components in Rat Kidney and Their Characterization, Mech. Ageing Dev. 97, 93–107.PubMedCrossRefGoogle Scholar
  29. 29.
    Bombardier, C., Laine, L., Reicin, A., Shapiro, D., Burgos-Vargas, R., Davis, B., Day, R., Ferraz, M.B., Hawkey, C.J., Hochberg, M.C., et al. (2000) Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis, N. Engl. J. Med. 343, 1520–1528.PubMedCrossRefGoogle Scholar
  30. 30.
    Singh, V.P., Patil, C.S., and Kulkarni, S.K. (2005) Differential Effect of Zileuton, a 5-Lipoxygenase Inhibitor, Against Nociceptive Paradigms in Mice and Rats, Pharmacol. Biochem. Behav. 81, 433–439.PubMedCrossRefGoogle Scholar
  31. 31.
    Hatley, M.E., Strinvasan, S., Reilly, K.B., Bolick, D.T., and Hedrick, C.C. (2003) Increased Production of 12/15 Lipoxygenase Eicosanoids Accelerates Monocyte/Endothelial Interactions in Diabetic db/db Mice, J. Biol. Chem. 278, 25369–25375.PubMedCrossRefGoogle Scholar
  32. 32.
    Wong, B.C.U., Wang, W.P., Cho, C.H., Fan, X.M., Lin, M.C.M., Kung, H.F., and Lam, S.K. (2001) 12-Lipoxygenase Inhibition Induced Apoptosis in Human Gastric Cancer Cells, Carcinogensis 22, 1349–1354.CrossRefGoogle Scholar
  33. 33.
    Kuhn, H., and Thiele, B.J. (1999) The Diversity of the Lipoxygenase Family, FEBS Lett. 449, 7–11.PubMedCrossRefGoogle Scholar
  34. 34.
    Schewe, T., Sadik, C., Klotz, L.O., Yoshimoto, T., Kuhn, H., and Sies, H. (2001) Polyphenols of Cocoa: Inhibition of Mammalian 15-Lipoxyogenase, Biol. Chem. 382, 1687–1696.PubMedCrossRefGoogle Scholar
  35. 35.
    Bolis, C.L., Piccolella, M., Valle, A.Z.D., and Rankin, J.C. (2001) Fish as Model in Pharmacological and Biological Research, Phamacological Res. 44, 265–280.Google Scholar
  36. 36.
    Froystad, M.K.M., Volden, V., Berg, T., and Gjoen, T. (2002) Metabolism of Oxidized and Chemically Modified Low Density Lipoproteins in Rainbow Trout-Clearance via Scavenger Receptors, Dev. Comp. Immunol. 26, 723–733.PubMedCrossRefGoogle Scholar
  37. 37.
    Wu, U.J., Hong, C.Y., Lin, S.J., Wu, P., and Shiao, M.S. (1998) Increase of Vitamin E Content in LDL and Reduction of Atherosclerosis in Cholesterol-Fed Rabbits by a Water-Soluble Antioxidant-Rich Fraction of Salvia miltiorrhiza, Arterioscler. Thromb. Vasc. Biol. 18, 481–486.PubMedGoogle Scholar
  38. 38.
    Sadik, C.D., Sies, H., and Schewe, T. (2003) Inhibition of 15-Lipoxygenases by Flavonoids: Structure-Activity Relations and Mode of Action, Biochem. Pharmacol. 65, 773–781.PubMedCrossRefGoogle Scholar

Copyright information

© AOCS Press 2005

Authors and Affiliations

  • Tsui-Yao Chen
    • 1
    • 2
  • Ming-Shi Shiao
    • 3
  • Bonnie Sun Pan
    • 1
  1. 1.Food Science DepartmentNational Taiwan Ocean UniversityKeelungRepublic of China Taiwan
  2. 2.Food Science DepartmentNational I-Lan UniversityI-LanTaiwan, Republic of China
  3. 3.Department of Medical Research and EducationVeterans General Hospital-TaipeiTaiwan, Republic of China

Personalised recommendations