Anti-inflammatory Effect of Bear's Gall in Rat Microglia

  • Joo, Seong-Soo (Department of Immunology, College of Pharmacy, Chung-Ang University) ;
  • Yoo, Yeong-Min (Department of Oriental Pathology, College of Oriental Medicine, Sangji University) ;
  • Lee, Seon-Goo (Department of Oriental Pathology, College of Oriental Medicine, Sangji University) ;
  • Lee, Do-Ik (Department of Immunology, College of Pharmacy, Chung-Ang University)
  • Published : 2005.02.25

Abstract

We hypothesize that bear's gall may have a certain role in anti-inflammation through a preventive effect of pro-inflammatory potentials. Secondly, we tried to connect the experimental results to Alzheimer's disease (AD), which chronic inflammation is a main cause of the disease. For this theme, we designed to elucidate the efficacy of bear's gall in suppressing the pro-inflammatory mediators, such as nitric oxide (NO) and $interleukin-1{\beta}\;(IL-1{\beta})$ in rat microglia. From the study, we concluded that bear's gall plays a positive role in suppressing such pro-inflammatory repertoire from rat microglia comparing to normal and positive control, such as culture media and cyclosporine. Interestingly, bear's gall showed a prolonged effect of anti-inflammation comparing with cyclosporine when time goes by up to 48h with a significant suppression at $1.2\;mg/m{\ell}$. Therefore, we can consider that bear's gall in part can be applied to AD therapy in that it suppresses the expression of pro-inflammatory mediators as well as its continued effect.

Keywords

References

  1. Lue, L.F., and Walker, D.G., Modeling Alzheimer's disease immune therapy mechanisms; interaction of human postmortem microglia with antibody-opsonized amyloid beta peptide. J Neurosci Res., 70, 599-610, 2002.
  2. Dickson, D.W., Lee, S.C, Mattiace, L.A., Yen, S.H., and Brosnan, C., Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia, 7,75-83, 1993.
  3. Selkoe, D.J., The molecular pathology of Alzheimer's disease. Neuron, 6, 487-498, 1991.
  4. Bayer, T.A., Wirths, O., Majtenyl, K., Hartmann, T., Multhaup, G., Beyreuther, K., and Czech, C., Key factors in Alzheimer's disease: $\beta$-amyloid precursor protein processing, metabolism, and intraneuronal transport. Brain Pathology, 11, 1-11, 2001.
  5. Banati, R.B., Gehrmann, J., Schubert, P., Kreutzberg, G.W., Cytotoxicity of microglia. Glia, 7, 111-118, 1996.
  6. Giulian, D., Ameboid microglia as effectors of inflammation in the central nervous system. J. Neuroscience. Res., 18, 155-171, 1987.
  7. Giulian, D., Baker, T.J., Shih, L., and Lachman, L.B., Interleukin-1 of the central nervous system is produced by ameboid microglia. J. Exp. Med, 164, 594, 1986.
  8. Rodrigues, C.M.P., Ma, X., Kren, B.T., and Streer, C.J., A novel role for ursodeoxycholic acid in inhibiting apotosis by modulating mitochondrial membrane perturbation. J. clin. Invest., 101(12), 2790-2799, 1998.
  9. Kim, W.G., Mohney, R.P., Wilson, B., Heohn, G.H., Liu, B., and Hong, J.S., Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: Role of microglia. J. Neurosci., 20, 6309-6316, 2000.
  10. Yanker, B.A., Duffy, L.K., and Kirschner, D.A., Neurotrophic and neurotoxic effects of amyloid $\beta$ protein: Reversal by tachykinin neuropeptide. Science, 250, 279-282, 1990.
  11. Gouras, G.K., Current theories for the molecular and cellular pathogenesis of Alzheimer's disease. Expert review in molecular medicine. Cambridge University Press, 2001.
  12. Chao, C.C.. Hu, S., Molitor, T.W., Shaskan, E.C., and Peterson, P.K., Activated microglia mediated neuronal cell injury via a nitric oxide mechanism. J. Immunol, 149, 2736-2741, 1992.
  13. Tanaka, H., Makino, Y., Miura, T., Hirano, F., Okamoto, K., Komura, K., Sato, Y., Makino, I., Ligand-independent activation of the glucocorticoid receptor by ursodeoxycholic acid. Repression of the IFN- gamma-induced MHC class II gene expression via a glucocorticoid receptor-dependent pathway. J. Immunology, 156,1601-1608, 1996.
  14. Calmus, Y.P., Podevin, P., Poupun, R., Dirrefntial effects of chenodeoxycholic and ursodeoxycholic acid on interleukin-1, interleukin-6, and tumor necrosis factor-$\alpha$ production by monocytes. Hepatology, 16,719-723, 1992.
  15. Lacaille, F., K Paradis, K., The immunosuppressive effect of ursodexycholic, a comparative in vitro study on human peripheral blood mononuclear cells. Hepatology, 18, 165-172, 1993.
  16. Ljubuncic, P., Fuhrman, B., Oiknine, J., Aviram, M., and Bomzon, A., Effect of deoxycholic acid and ursodeoxycholic acid on lipid peroxidation in cultured macrophages. Gut., 39(3), 475-478, 1996.
  17. Paresce, D.M., H, Chung, and Maxfield., Slow degradation of aggregates of the Alzheimer's disease amyloid beta-protein by microglial cells. J. Biol. Chem. 272, 29390-29397, 1997.
  18. Lin, T.J., Hirji, N., Stenton, G.R., Gilchrist, M., Grill, B.J., Schreiber, A.D., and Befus, A.D., Activation of Macropharge CD8: Pharmacological Studies of TNF and IL-I$\beta$ Production. J. Immunol., 164, 1783-1792, 2000.
  19. Possel, H., Noack, H., Putzke, J., Wolf, G., and Sies, H., Selective upregulation of inducible Nitric Oxide Synthase (iNOS) by lipopolysaccharide(LPS) and cytokines in microglia. Glia, 32, 51-59, 2000.
  20. Meda, L., Cassatella, M.A., Szendrei, G.I., Baron, P., Villalba, M., Ferrari, D., and Rossi, F., Activation of microglia cell by $\beta$-amyloid protein and interferon-$\gamma$. Nature, 374, 647-650, 1995.
  21. Benveniste, E.N., Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am. J. Physiol, 263, C1-16, 1992.
  22. Strijbos, P.J., and Rothwell, N.J., Interleukin-1beta attenuates excitatory amino acid-induced neurodegeneration in vitro: involvement of nerve growth factor. J. Neurosci., 153, 3468-3474, 1995.
  23. Lue, L., Rydel, R., Brigham, E.F., Yang, L., Hampek, H., Murphy, G.M., Brachova, L., Yan, S., Walker, D.G., Shen, Y., and Rogers, J., Imflammatory receptories of Alzheimer's disease and non demented elderly microglia in vitro. Glia., 35, 72-79, 2001.
  24. Mrak, R.E., Sheng, J.G., Griffin, W.S.T., Glial cytokines in Alzheimer's disease: reveiwand pathogenic implication. Hum. Pathol., 26, 816-823, 1995. https://doi.org/10.1016/0046-8177(95)90001-2
  25. Forloni, G., Demichelli, F., Giorgi, S., Bendotti, C., and Angeretti, N., Expression of amyloid precursor protein mRNAs in endothelial, neuronal, and glial cell: modulation by interleukin-1, Brain. Res., 16, 128-134, 1992.
  26. Mrak, R.E., Sheng, J.G., Griffin, W.S.T., Glial cytokines in Alzheimer's disease: reveiwand pathogenic implication. Hum. Pathol., 26, 816-823, 1995.
  27. Sheng, J.G., Ito, K., Skinner, R.D., Mrak, C.R., Van Eldik, L.J., Griffin, W.S.T., In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis. Neurobiol. Aging.,17, 761-766, 1996.
  28. Jaffrey, S.R., and Snyder, S.H., Nitric oxide: a nral messenger. Annu. Rev. Cell. Dev., 11, 417-440, 1995.
  29. Varadarajan, S., Yatin, S., Aksenova, M., and Butterfield, D.A., Review: Alzheimer's amyloid beta-peptide associated free radical oxidative stress and neurotoxicity. J. Structural Biol., 130, 184-208, 2000.
  30. Bowie, A., and O'Neill, L.A.J., Oxidative stress and nuclear Pactor-$\kappa$B activation; a reassessment of the evidence in the light of recent discoveries. Biochemical Pharmacology, 59, 13-23, 2000. https://doi.org/10.1016/S0006-2952(99)00296-8