Tribulus terrestris Suppresses the Lipopolysaccharide-Induced Inflammatory Reaction in RAW264.7 Macrophages through Heme Oxygenase-1 Expressions

  • Kim, Jai Eun (Department of Pathology, College of Korean Medicine, Dongguk University)
  • Received : 2014.01.28
  • Accepted : 2014.01.29
  • Published : 2014.02.25

Abstract

The fruit of Tribulus terrestris L. (Zygophyllaceae) is an important source of traditional Korean and Chinese medicines. In this study, NNMBS223, consisting of the ethanol extract of T. terrestris, showed potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS223 in suppressing the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and production of iNOS-derived nitric oxide (NO), COX-2-derived prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated macrophages. In addition, NNMBS223 induced expression of heme oxygenase (HO)-1 through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. The effects of NNMBS223 on LPS-induced production of NO and PGE2 were partially reversed by the HO activity inhibitor tin protoporphyrin (SnPP). These findings suggest that Nrf2-dependent increases in expression of HO-1 induced by NNMBS223 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

Keywords

References

  1. Kostova, I., Dinchev, D., Rentsch, G.H., Dimitrov, V., Ivanova, A. Two new sulfated furostanol saponins from Tribulus terrestris. Z Naturforsch C 57: 33-38, 2002.
  2. Akram, M., Asif, H.M., Akhtar, N., Shah, P.A., Uzair, M., Shaheen, G., Shamim, T., Ali Shah, S.M., Ahmad, K. Tribulus terrestris Linn.: a review article. J Med Plants Res 5: 3601-3605, 2011.
  3. Vesilada, E., Honda, G., Sezik, E., Tabata, M., Fujita, T., Tanaka, T., Takeda, Y., Takaishi, Y. Traditional medicine in Turkey. V. Folk medicine in the Inner Taurus Mountains. J Ethnopharmacol 46: 133-152, 1995. https://doi.org/10.1016/0378-8741(95)01241-5
  4. Wu, T.S., Shi, L.S., Kuo, S.C. Alkaloids and other constituents from Tribulus terrestris. Phytochemistry 50: 1411-1415, 1999. https://doi.org/10.1016/S0031-9422(97)01086-8
  5. Kostova, I., Dinchev, D. Saponins in Tribulus terrestris - chemistry and bioactivity. Phytochem Rev 4: 111-137, 2005. https://doi.org/10.1007/s11101-005-2833-x
  6. Maines, M.D. The oxygenase system: a regular of second messenger gases. Annu Rev Pharmacol Toxicol 37: 517-554, 1997. https://doi.org/10.1146/annurev.pharmtox.37.1.517
  7. Zedler, S., Faist, E. The impact of endogenous triggers on trauma-associated inflammation. Curr Opin Crit Care 12: 595-601, 2006. https://doi.org/10.1097/MCC.0b013e3280106806
  8. Vane, J.R., Mitchell, J.A., Appleton, I., Tomlinson, A., Bishop-Bailey, D., Croxtall, J., Willoughby, D.A. Inducible isoforms of cyclooxygenase and nitric oxide synthase in inflammation. Proc Natl Acad Sci USA 91: 2046-2050, 1994. https://doi.org/10.1073/pnas.91.6.2046
  9. Cheon, H., Rho, Y.H., Choi, S.J., Lee, Y.H., Song, G.G., Sohn, J., Won, N.H., Ji, J.D. Prostaglandin E2 augments IL-10 signaling and function. J Immunol 15: 1092-1100, 2006.
  10. Wolf, A.M., Wolf, D., Rumpold, H., Ludwiczek, S., Enrich, B., Gastl, G., Weiss, G., Tilg, H. The kinase inhibitor imatinib mesylate inhibits TNF-alpha production in vitro and prevents TNF-dependent acute hepatic inflammation. Proc Natl Acad Sci USA 20: 13622-13627, 2005.
  11. Maines, M.D. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J 2: 2557-2568, 1988.
  12. Lee, T.S., Tsai, H.L., Chau, L.Y. Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflamatory effect of low dose 15-deoxy-delta-12,14-prostaglandin J2. J Biol Chem 278: 19325-19330, 2003. https://doi.org/10.1074/jbc.M300498200
  13. Wiesel, P., Foster, L.C., Pellacani, A., Layne, M.D. Hsieh, C.M. Huggins, G.S. Strauss, P., Yet, S.F., Perrella, M.A. Thioredoxin facilitates the induction of heme oxygenase-1 in response to inflammatory mediators. J Biol Chem 275: 24840-24846, 2000. https://doi.org/10.1074/jbc.M000835200
  14. Morse, D., Pischke, S.E., Zhou, Z., Davis, R.J., Flavell, R.A., Loop, T. Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem 278: 36993-36998, 2003. https://doi.org/10.1074/jbc.M302942200
  15. Poss, K.D., Tonegawa, S. Reduced stress defense in heme oxygenase- 1 deficient cells. Proc Natl Acad Sci USA 94: 10925-10930, 1997. https://doi.org/10.1073/pnas.94.20.10925
  16. Shen, G., Kong, A.N. Nrf2 plays an important role in coordinated regulation of Phase II drug metabolism enzymes and Phase III drug transporters. Biopharm Drug Dispos 30: 345-355, 2009. https://doi.org/10.1002/bdd.680
  17. Lee, D.S., Jeong, G.S., Li, B., Park, H., Kim, Y.C. Anti-inflammatory effects of sulfuretin from Rhus verniciflua Stokes via the induction of heme oxygenase-1 expression in murine macrophages. Int Immunopharmacol 10: 855-858, 2010.
  18. Hammoda, H.M., Ghazy, N.M., Harraz, F.M., Radwan, M.M., ElSohly, M.A., Abdallah, I.I. Chemical constituents from Tribulus terrestris and screening of their antioxidant activity. Phytochemistry 92: 153-159, 2013. https://doi.org/10.1016/j.phytochem.2013.04.005
  19. Heidari, M.R., Mehrabani, M., Pardakhty, A., Khazaeli, P., Zahedi, M.J., Yakhchali, M., Vahedian, M. The analgesic effect of Tribulus terrestris extract and comparison of gastric ulcerogenicity of the extract with indomethacine in animal experiments. Ann N Y Acad Sci 1095: 418-427, 2007. https://doi.org/10.1196/annals.1397.045
  20. Ehrman, T.M., Barlow, D.J., Hylands, P.J. In silico search for multitarget anti-inflammatories in Chinese herbs and formulas. Bioorg Med Chem 18: 2204-2218, 2010. https://doi.org/10.1016/j.bmc.2010.01.070
  21. Hong, C.H., Hur, S.K., Oh, O.J., Kim, S.S., Nam, K.A., Lee, S.K. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J Ethnopharmacol 83: 153-159, 2002. https://doi.org/10.1016/S0378-8741(02)00205-2
  22. Otterbein, L.E., Bach, F.H., Alam, J., Soares, M., Tao Lu, H., Wysk, M., Davis, R.J., Flavell, R.A., Choi, A.M. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6: 422-428, 2000. https://doi.org/10.1038/74680