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Effect of Tetramethylpyrazine on Pro-Inflammatory Cytokine Expressions in Mouse Brain Tissue following Intracerebroventricular Lipopolysaccharide Treatment

Tetramethylpyrazine이 LPS의 뇌실주입에 따른 생쥐 뇌조직의 Pro-Inflammatory Cytokines 발현에 미치는 영향

  • Choi, Yong-Seok (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Won, Jong-Woo (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Yoo, Inwoo (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Shin, Jung-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kim, Seong-Joon (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Sohn, Nak-Won (Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
  • 최용석 (경희대학교 동서의학대학원 한의과학전공) ;
  • 원종우 (경희대학교 동서의학대학원 한의과학전공) ;
  • 유인우 (경희대학교 동서의학대학원 한의과학전공) ;
  • 신정원 (경희대학교 동서의학대학원 한의과학전공) ;
  • 김성준 (경희대학교 동서의학대학원 한의과학전공) ;
  • 손낙원 (경희대학교 동서의학대학원 한의과학전공)
  • Received : 2012.12.24
  • Accepted : 2013.01.12
  • Published : 2013.01.30

Abstract

Objectives : Tetramethylpyrazine (TMP) is an active ingredient in Ligusticum wallichii and has a wide range of neuroprotection effects. This study investigated anti-neuroinflammatory effect of TMP on brain regions in intracerebroventricular (i.c.v.) lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : TMP was administered intraperitoneally at doses of 10, 20, and 30 mg/kg at 1 h prior to LPS (3 mg/kg) i.c.v. injection. mRNA level of pro-inflammatory cytokines, including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$ and IL-6, was measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Cyclooxygenase-2 (COX-2) positive cells in the hypothalamus was also observed using immunohistochemistry at 24 h after the LPS injection. Results : At a dose of 30 mg/kg TMP significantly attenuated up-regulation of TNF-${\alpha}$ and IL-$1{\beta}$ mRNA in the cerebral cortex and IL-$1{\beta}$ mRNA in the hippocampus. In the hypothalamus, doses of 20 mg/kg and 30 mg/kg TMP significantly attenuated up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 mRNA induced by the LPS injection. In addition, TMP (30 mg/kg) significantly reduced the number of COX-2 positive cells in the hypothalamus. Conclusion : These results indicate that TMP has an anti-inflammatory effect on neuroinflammation, especially in the hypothalamus, induced by LPS i.c.v. injection and suggest that TMP-containing Ligusticum wallichii may play a modulatory role on the systemic responses following hypothalamic inflammation.

Keywords

References

  1. Szelenyi J. Cytokines and the central nervous system. Brain Res Bull. 2001 ; 54 : 329-38. https://doi.org/10.1016/S0361-9230(01)00428-2
  2. Banks WA, Kastin AJ. Relative contributions of peripheral and central sources to levels of IL-1 alpha in the cerebral cortex of mice: Assessment with species-specific enzyme immunoassays. J Neuroimmunol. 1997 ; 79 : 22-8. https://doi.org/10.1016/S0165-5728(97)00103-3
  3. Sternberg EM. Neural-immune interactions in health and disease. J Clin Invest. 1997 ; 100 : 2641–7. https://doi.org/10.1172/JCI119807
  4. Rosenberg PB. Clinical aspects of inflammation in Alzheimer's disease. Int Rev Psychiatry. 2005 ; 17 : 503-14. https://doi.org/10.1080/02646830500382037
  5. Shih YH, Wu SL, Chiou WF, Ku HH, Ko TL, Fu YS. Protective effects of tetramethylpyrazine on kainate-induced excitotoxicity in hippocampal culture. Neuroreport. 2002 ; 13 : 515-9. https://doi.org/10.1097/00001756-200203250-00032
  6. Zhang Z, Wei T, Hou J, Li G, Yu S, Xin W.Iron-induced oxidative damage and apoptosis in cerebellar granule cells: attenuation by tetramethylpyrazine and ferulic acid. Eur J Pharmacol. 2003 ; 467 : 41-7. https://doi.org/10.1016/S0014-2999(03)01597-8
  7. Cheng XR, Zhang L, Hu JJ, Sun L, Du GH. Neuroprotective effects of tetramethylpyrazine on hydrogen peroxide-induced apoptosis in PC12 cells. Cell Biol Int. 2007 ; 31 : 438-43. https://doi.org/10.1016/j.cellbi.2006.10.001
  8. Li SY, Jia YH, Sun WG, Tang Y, An GS, Ni JH, Jia HT.Stabilization of mitochondrial function by tetramethylpyrazine protects against kainateinduced oxidative lesions in the rat hippocampus. Free Radic Biol Med. 2010 ; 48 : 597-608. https://doi.org/10.1016/j.freeradbiomed.2009.12.004
  9. Liao SL, Kao TK, Chen WY, Lin YS, Chen SY, Raung SL, Wu CW, Lu HC, Chen CJ. Tetramethylpyrazine reduces ischemic brain injury in rats. Neurosci Lett. 2004 ; 372 : 40-5. https://doi.org/10.1016/j.neulet.2004.09.013
  10. Kao TK, Ou YC, Kuo JS, Chen WY, Liao SL, Wu CW, Chen CJ, Ling NN, Zhang YH, Peng WH. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats. Neurochem Int. 2006 ; 48 : 166-76. https://doi.org/10.1016/j.neuint.2005.10.008
  11. Hsiao G, Chen YC, Lin JH, Lin KH, Chou DS, Lin CH, Sheu JR. Inhibitory mechanisms of tetramethylpyrazine in middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Planta Med. 2006 ; 72 : 411-7. https://doi.org/10.1055/s-2005-917242
  12. Chang Y, Hsiao G, Chen SH, Chen YC, Lin JH, Lin KH, Chou DS, Sheu JR. Tetramethylpyrazine suppresses HIF-1alpha, TNF-alpha, and activated caspase-3 expression in middle cerebral artery occlusion-induced brain ischemia in rats. Acta Pharmacol Sin. 2007 ; 28 : 327-33. https://doi.org/10.1111/j.1745-7254.2007.00514.x
  13. Zhu XL, Xiong LZ, Wang Q, Liu ZG, Ma X, Zhu ZH, Hu S, Gong G, Chen SY. Therapeutic time window and mechanism of tetramethylpyrazine on transient focal cerebral ischemia/ reperfusion injury in rats. Neurosci Lett. 2009 ; 449 : 24-7. https://doi.org/10.1016/j.neulet.2008.09.007
  14. Xiao X, Liu Y, Qi C, Qiu F, Chen X, Zhang J, Yang P. Neuroprotection and enhanced neurogenesis by tetramethylpyrazine in adult rat brain after focal ischemia. Neurol Res. 2010 ; 32 : 547-55. https://doi.org/10.1179/174313209X414533
  15. Yang J, Li J, Lu J, Zhang Y, Zhu Z, Wan H. Synergistic protective effect of astragaloside IV-tetramethylpyrazine against cerebral ischemic-reperfusion injury induced by transient focal ischemia. J Ethnopharmacol. 2012 ; 140 : 64-72. https://doi.org/10.1016/j.jep.2011.12.023
  16. Sun Y, Yu P, Zhang G, Wang L, Zhong H, Zhai Z, Wang L, Wang Y. Therapeutic effects of tetramethylpyrazine nitrone in rat ischemic stroke models. J Neurosci Res. 2012 ; 90 : 1662-9. https://doi.org/10.1002/jnr.23034
  17. Tang Q, Han R, Xiao H, Shen J, Luo Q, Li J. Neuroprotective effects of tanshinone IIA and/or tetramethylpyrazine in cerebral ischemic injury in vivo and in vitro. Brain Res. 2012 ; 1488 : 81-91. https://doi.org/10.1016/j.brainres.2012.09.034
  18. Gao C, Liu X, Liu W, Shi H, Zhao Z, Chen H, Zhao S. Anti-apoptotic and neuroprotective effects of Tetramethylpyrazine following subarachnoid hemorrhage in rats. Auton Neurosci. 2008 ; 141 : 22-30. https://doi.org/10.1016/j.autneu.2008.04.007
  19. Fan LH, Wang KZ, Cheng B, Wang CS, Dang XQ. Anti-apoptotic and neuroprotective effects of Tetramethylpyrazine following spinal cord ischemia in rabbits. BMC Neurosci. 2006 ; 7 : 48. https://doi.org/10.1186/1471-2202-7-48
  20. Liang Y, Yang QH, Yu XD, Jiang DM. Additive effect of tetramethylpyrazine and deferoxamine in the treatment of spinal cord injury caused by aortic cross-clamping in rats. Spinal Cord. 2011 ; 49 : 302-6. https://doi.org/10.1038/sc.2010.113
  21. Fan L, Wang K, Shi Z, Die J, Wang C, Dang X. Tetramethyl- pyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury. J Vasc Surg. 2011 ; 54 : 192-200. https://doi.org/10.1016/j.jvs.2010.12.030
  22. Hu JZ, Huang JH, Xiao ZM, Li JH, Li XM, Lu HB. Tetramethyl- pyrazine accelerates the function recovery of traumatic spinal cord in rat model by attenuating inflammation. J Neurol Sci. 2013 ; 324 : 94-9. https://doi.org/10.1016/j.jns.2012.10.009
  23. Fu X, Zunich SM, O'Connor JC, Kavelaars A, Dantzer R, Kelley KW. Central administration of lipopolysaccharide induces depressive-like behavior in vivo and activates brain indoleamine 2,3 dioxygenase in murine organotypic hippocampal slice cultures. J Neuroinflammation. 2010 ; 7 : 43. https://doi.org/10.1186/1742-2094-7-43
  24. Harry GJ, Kraft AD. Neuroinflammation and microglia: considerations and approaches for neurotoxicity assessment. Expert Opin Drug Metab Toxicol. 2008 ; 4 : 1265-77. https://doi.org/10.1517/17425255.4.10.1265
  25. Konat GW, Kielian T, Marriott I. The role of Toll-like receptors in CNS response to microbial challenge. J Neurochem. 2006 ; 99 : 1–12.
  26. Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT. Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia. 2007 ; 55 : 453-62. https://doi.org/10.1002/glia.20467
  27. Jeong HK, Jou I, Joe EH. Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra. Exp Mol Med. 2010 ; 42 : 823-32. https://doi.org/10.3858/emm.2010.42.12.085
  28. Cai D, Liu T. Hypothalamic inflammation: a double-edged sword to nutritional diseases. Ann NY Acad Sci. 2011 ; 1243 : E1-39. https://doi.org/10.1111/j.1749-6632.2011.06388.x
  29. Granger JI, Ratti PL, Datta SC, Raymond RM, Opp MR. Sepsis-induced morbidity in mice: Effects on body temperature, body weight, cage activity, social behavior and cytokines in brain. Psychoneuroendocrinology. 2012 ; doi :10.1016/j.psyneuen.2012.10.010.
  30. Harden LM, du Plessis I, Roth J, Loram LC, Poole S, Laburn HP. Differences in the relative involvement of peripherally released interleukin (IL)-6, brain IL-$1\beta$ and prostanoids in mediating lipopolysaccharide-induced fever and sickness behavior. Psychoneuroendocrinology. 2011 ; 36 : 608-22. https://doi.org/10.1016/j.psyneuen.2010.09.003
  31. Mancuso C, Navarra P, Preziosi P. Roles of nitric oxide, carbon monoxide, and hydrogen sulfide in the regulation of the hypothalamic-pituitary-adrenal axis. J Neurochem. 2010 ; 113 : 563-75. https://doi.org/10.1111/j.1471-4159.2010.06606.x
  32. Grinevich V, Ma XM, Herman JP, Jezova D, Akmayev I, Aguilera G. Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats. J Neuroendocrinol. 2001 ; 13 : 711-23. https://doi.org/10.1046/j.1365-2826.2001.00684.x
  33. Kim HC. Herbal Pharmacology. Seoul Gipmoon-Dang. 2001 : 318-20.
  34. Choi SH, Aid S, Bosetti F. The distinct roles of cyclooxygenase-1 and –2 in neuroinflammation: implications for translational research. Trends Pharmacol Sci. 2009 ; 30 : 174-81. https://doi.org/10.1016/j.tips.2009.01.002
  35. Zheng CY, Xiao W, Zhu MX, Pan XJ, Yang ZH, Zhou SY. Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis. Int J Oncol. 2012 ; 40 : 2029-37.
  36. He X, Zheng Z, Yang X, Lu Y, Chen N, Chen W. Tetramethylpyrazine attenuates PPAR-$\gamma$ antagonist-deteriorated oxazolone-induced colitis in mice. Mol Med Report. 2012 ; 5 : 645-50.
  37. Liang SD, Gao Y, Xu CS, Xu BH, Mu SN. Effect of tetramethylpyrazine on acute nociception mediated by signaling of P2X receptor activation in rat. Brain Res. 2004 ; 995 : 247-52. https://doi.org/10.1016/j.brainres.2003.09.070