Banhabaikchulcheunma-tang Down-regulates LPS-induced Production of Pro-inflammatory Cytokines

  • Kim, Yun-Ha (Vestibulocochlear Research Center & Department of Microbiology, School of Medicine, Wonkwang University) ;
  • Cho, Kwang-Ho (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Moon, Byung-Soon (Professional Graduate School of Oriental Medicine, Wonkwang University)
  • Published : 2009.02.25


Banhabaikchulcheunma-tang (BBCT), a prescription composed of thirteen herbal mixtures, has been widely used in the treatment of brain disorders in Oriental Medicine. However, the mechanisms by which the formula affects on the production of pro-inflammatory cytokines in cerebral infarction (CI) patients remain unknown yet. The levels of secretory protein of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interlukin (IL)-1b, and IL-6, were significantly increased in lipopolysaccharide (LPS)-stimulated THP-1 differentiated macrophage-like (THP-1/M) cells and Peripheral blood mononuclear cells (PBMCs) from CI patients. However, pretreatment with BBCT significantly inhibited the secretion of pro-inflammatory cytokines, including TNF-a, IL-1b, and IL-6, in THP-1/M cells and PBMCs from CI patients with stimulus. Thus, these data indicate that BBCT may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression on the production of pro-inflammatory cytokines.


  1. Bemeur, C., Ste-Marie, L., Desjardins, P., Vachon, L., Butterworth, R.F., Hazell, A.S., Montgomery, J. Dehydroascorbic acid normalizes several markers of oxidative stress and inflammation in acute hyperglycemic focal cerebral ischemia in the rat. Neurochem Int. 46: 399-407, 2005
  2. Lee, J.C., Cho, G.S., Kim, H.J., Lim, J.H., Oh, Y.K., Nam, W., Chung, J.H., Kim, W.K. Accelerated cerebral ischemic injury by activated macrophages/microglia after lipopolysaccharide microinjection into rat corpus callosum. Glia 50: 168-181, 2005
  3. Kim, Y., So, H.S., Youn, M.J., Kim, H.J., Woo, W.H., Shin, S.H., Lee, I., Moon, B.S., Cho, K.H., Park, R. Anti-inflammatory effect of Sasim extracts in PHA-stimulated THP-1 and peripheral blood mononuclear cells from CI patients. J Ethnopharmacol. 112(1):32-39, 2007
  4. Barone, F.C., Schmidt, D.B., Hillegass, L.M., Price, W.J., White, R.F., Feuerstein, G.Z., Clark, R.K., Lee, E.V., Griswold, D.E., Sarau, H.M. Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia. Stroke 23: 1337-1347, 1992
  5. Kochanek, P.M., Hallenbeck, J.M. Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23: 1367-1379, 1992
  6. Wang, P.Y., Kao, C.H., Mui, M.Y., Wang, S.J. Leukocyte infiltration in acute hemispheric ischemic stroke. Stroke 24: 236-240, 1993
  7. Garcia, J.H., Liu, K.F., Yoshida, Y., Chen, S., Lian, J. Brain microvessels: factors altering their patency after the occlusion of a middle cerebral artery (Wistar rat). Am J Pathol. 145: 728-740, 1994
  8. Lucas, S.M., Rothwell, N.J., Gibson, R.M. The role of inflammation in CNS injury and disease. Br J Pharmacol. 1: S232-S240, 2006
  9. Kim, Y., So, H.S., Youn, M.J., Kim, E.S., Song, M.S., Chai, K.Y., Woo, W.H., Cho, K.H., Moon, B.S., Park, R. Anti-inflammatory effect of So-Pung-Tang, a Korean traditional prescription for cerebral infarction patients. J Ethnopharmacol. 114(3):425-431, 2007
  10. Castillo, J., Leira, R. Predictors of deteriorating cerebral infarct: role of inflammatory mechanisms. Would its early treatment be useful? Cerebrovasc Dis. 1: 40-48, 2001
  11. Nilupul, P.M., Ma, H.K., Arakawa, S., Howells, D.W., Markus, R., Rowe, C.C., Donnan, G.A. Inflammation following stroke. J Clin Neurosci. 13: 1-8, 2006
  12. Yamasaki, Y., Matsuo, Y., Zagorski, J., Matsuura, N., Onodera, H., Itoyama, Y., Kogure, K. New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats. Brain Res. 759: 103-111, 1997
  13. Kariko, K., Weissman, D., Welsh, F.A. Inhibition of toll-like receptor and cytokine signaling--a unifying theme in ischemic tolerance. J Cereb Blood Flow Metab. 24: 1288-1304, 2004
  14. Nakamura, K., Ueno, T., Yamamoto, H., Iguro, Y., Yamada, K., Sakata, R. Relationship between cerebral injury and inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass. Cytokine 29: 95-104, 2005
  15. Gao, N., Yu, S., Xu, J. Improving effect of rhizoma Gastrodiae on learning and memory of senile rats. Zhongguo Zhong Yao Za Zhi. 20(9):562-563, 1995
  16. Chang, Y.H., Kim, C., Jung, M., Lim, Y.H., Lee, S., Kang, S. Inhibition of melanogenesis by selina-4(14),7(11)-dien-8-one isolated from Atractylodis Rhizoma Alba. Biol Pharm Bull. 30(4):719-723, 2007
  17. Naval, M.V., G$\'{e}$mez-Serranillos, M.P., Carretero, M.E., Villar, A.M. Neuroprotective effect of a ginseng (Panax ginseng) root extract on astrocytes primary culture. J Ethnopharmacol. 112(2):262-270, 2007
  18. Kim, E.H., Jang, M.H., Shin, M.C., Shin, M.S., Kim, C.J. rotective effect of aqueous extract of Ginseng radix against 1-methyl-4-phenylpyridinium-induced apoptosis in PC12 cells. Biol Pharm Bull. 26(12):1668-1673, 2003
  19. Liou, C.J., Huang, W.C., Tseng, J. Long-term oral administration of ginseng extract modulates humoral immune response and spleen cell functions. Am J Chin Med. 33(4):651-661, 2005
  20. Liou, C.J., Huang, W.C., Tseng, J. Short-term oral administration of ginseng extract induces type-1 cytokine production. Immunopharmacol Immunotoxicol. 28(2):227-240, 2006
  21. Chang, H.K., Jang, M.H., Lim, B.V., Lee, T.H., Shin, M.C., Shin, M.S., Kim, H., Kim, Y.P., Kim, E.H., Kim, C.J. Administration of Ginseng radix decreases nitric oxide synthase expression in the hippocampus of streptozotocin-induced diabetic rats. Am J Chin Med. 32(4):497-507, 2004
  22. Zhao, P., Su, G., Xiao, X., Hao, E., Zhu, X., Ren, J. Chinese medicinal herb Radix Astragali suppresses cardiac contractile dysfunction and inflammation in a rat model of autoimmune myocarditis. Toxicol Lett. Aug 20, 2008. [Epub ahead of print]
  23. Ryu, M., Kim, E.H., Chun, M., Kang, S., Shim, B., Yu, Y.B., Jeong, G., Lee, J.S. Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk. J Ethnopharmacol. 115(2):184-193, 2008
  24. Huang, Y.T., Huang, D.M., Chueh, S.C., Teng, C.M., Guh, J.H. Alisol B acetate, a triterpene from Alismatis rhizoma, induces Bax nuclear translocation and apoptosis in human hormone-resistant prostate cancer PC-3 cells. Cancer Lett. 231(2):270-278, 2006
  25. Kim, H.J., Kong, M.K., Kim, Y.C. Beneficial effects of Phellodendri Cortex extract on hyperglycemia and diabetic nephropathy in streptozotocin-induced diabetic rats. BMB Rep. 41(10):710-715, 2008
  26. Stoll, G., Jander, S., Schroeter, M. Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol. 56: 149-171, 1998
  27. Zheng, Z., Yenari, M.A. Post-ischemic inflammation: molecular mechanisms and therapeutic implications. Neurol Res. 26: 884-892, 2004
  28. Bevilacqua, M.P., Pober, J.S., Wheeler, M.E., Cotran, R.S., Gimbrone, M.A. Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 76: 2003-2011, 1985
  29. Dihne, M., Block, F. Focal ischemia induces transient expression of IL-6 in the substantia nigra pars reticulata. Brain Res. 889: 165-173, 2001
  30. Park, Y.G., Kang, S.K., Kim, W.J., Lee, Y.C., Kim, C.H. Effects of TGF-beta, TNF-alpha, IL-beta and IL-6 alone or in combination, and tyrosine kinase inhibitor on cyclooxygenase expression, prostaglandin E2 production and bone resorption in mouse calvarial bone cells. Int J Biochem Cell Biol. 36: 2270-2280, 2004
  31. Hosomi, N., Ban, C.R., Naya, T., Takahashi, T., Guo, P., Song, X.Y., Kohno, M. Tumor necrosis factor-alpha neutralization reduced cerebral edema through inhibition of matrix metalloproteinase production after transient focal cerebral ischemia. J Cereb Blood Flow Metab. 25: 959-967, 2005
  32. Dawson, D.A., Martin, D., Hallenbeck, J.M. Inhibition of tumor necrosis factor-alpha reduces focal cerebral ischemic injury in the spontaneously hypertensive rat. Neurosci Lett. 218: 41-44, 1996
  33. Shohami, E., Bass, R., Wallach, D., Yamin, A., Gallily, R. Inhibition of tumor necrosis factor alpha (TNF alpha) activity in rat brain is associated with cerebroprotection after closed head injury. J Cereb Blood Flow Metab. 16: 378-384, 1996
  34. Loddick, S.A., Rothwell, N.J. Neuroprotective effects of human recombinant interleukin-1 receptor antagonist in focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab. 16: 932-940, 1996
  35. Relton, J.K., Martin, D., Thompson, R.C., Russell, D.A. Peripheral administration of Interleukin-1 Receptor antagonist inhibits brain damage after focal cerebral ischemia in the rat. Exp Neurol. 138: 206-213, 1996
  36. Stroemer, R.P., Rothwell, N.J. Cortical protection by localized striatal injection of IL-1ra following cerebral ischemia in the rat. J Cereb Blood Flow Metab. 17: 597-604, 1997