Skip to main content
Log in

The inhibitory effects of cholalic acid and hyodeoxycholalic acid on the expression of TNFα and IL-1β after cerebral ischemia in rats

  • Research Article
  • Drug Efficacy and Safety
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Previous studies have shown that Qing Kai Ling, a traditional Chinese medicine, was able to effectively prevent the inflammation from cerebral ischemia (Chen et al., 2002). The cholalic acid and hyodeoxycholalic acid (cholalic acid mixture) was major active components in Qing Kai Ling. To study the effects of cholalic acid mixture on the damage cascade of cerebral ischemia, rat model of focal cerebral ischemia was established by permanent occlusion of left middle cerebral artery. We found that the administration of cholalic acid mixture could reduce the ischemic infarct size after 24 h of ischemia, and cholalic acid mixture could be detected in cerebrospinal fluid after 2h of administration. We also found that the concentrations of tumor necrosis factor-alpha and interlukin-1beta in rat brain were significantly lower when compared to the untreated animals after 12 h and 24 h of ischemia. The concentrations of von Willebrand factor and neuron specific enolase in the plasma were remarkably decreased in cholalic acid mixture treated animals than in the untreated ones after 12h of ischemia. Our results suggested that cholalic acid mixture is able to decrease the expression of inflammation factors including tumor necrosis factor-alpha and interlukin-1beta after focal cerebral ischemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

(TNF-α):

tumor necrosis factor-alpha

(IL-1β):

interlukin-1 beta

(NMDA):

N-methyl-D-aspartate

(ICAM-1):

intercellular adhensive molecular-1

(vWF):

von Willebrand factor

(NSE):

neuron-specific enolase

(QKL):

Qing Kai Ling

(MCAO):

middle cerebral artery occlusion

(ECA):

external carotid artery

(ICA):

internal carotid artery

(RIA):

Radioimmunoassay

(ip.):

intra-peritoneally

(BBB):

brain blood barrier

References

  • Barber, P. A., Auer, R. N., Buchan, A. M., and Sutherland, G. R., Understanding and managing ischemic stroke. Can. J. Physiol. Pharmacol., 79, 283–296 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Barone, F. C., Clark, R. K., Price, W. J., White, R. F., Feuerstein, G. Z., Storer, B. L., and Ohlstein, E. H., Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia. Brain Res., 623, 77–82 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Barone, F. C., Arvin, B., White, R. F., Miller, A., Webb, C. L., Willette, R. N., Lysko, P. G., and Feuerstein, G. Z., Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke, 28, 1233–1244 (1997).

    PubMed  CAS  Google Scholar 

  • Botker, H. E. and Ingerslev, J., Plasma concentrations of von Willebrand factor in patients with anginapectoris secondary to coronary atherosclerosis or cardiac syndrome. Thromb. Res., 97, 519–523 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Chen, X., Howard, O. M., Yang, X., Wang, L., Oppenheim, J. J., and Krakauer, T., Effects of Shuanghuanglian and Qingkailing, two multi-components of traditional Chinese medicinal preparations, on human leukocyte function. Life Sci., 70, 2897–2913 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Clemens, J. A., Stephenson, D. T., Dixon, E. P., Smalstig, E. B., Mincy, R. E., Rash, K. S., and Little, S. P., Global cerebral ischemia activates nuclear factor-kappa B prior to evidence of DNA fragmentation. Brain Res. Mol. Brain Res., 48, 187–196 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Dai, K., Gao, W., and Ruan, C., The Sma I polymorphism in the von Willebrand factor gene associated with acute ischemic stroke. Thromb. Res., 104, 389–395 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Emsley, H. C. and Tyrrell, P. J., Inflammation and infection in clinical stroke. J. Cereb. Blood Flow Metab., 22, 1399–1419 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Gong, C., Qin, Z., Betz, A. L., Liu, X. H., and Yang, G. Y., Cellular localization of tumor necrosis factor alpha following focal cerebral ischemia in mice. Brain Res., 801, 1–8 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Hatfield, R. H. and McKernan, R. M., CSF neuron-specific enolase as a quantitative marker of neuronal damage in a rat stroke model. Brain Res., 577, 249–252 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Hua, Q., Zhu, X-L., Li, P-T., Tang, H-L., Cai, D-Y., Xu, Y., Jia, X., Chen, J., and Shen, Y., Refined qing kai ling, traditional chinese medicinal preparation, reduces ischemic stroke-induced infarct size and neurological deficits and increases expression of endothelial nitric oxide synthase. Biol. Pharm. Bull., 31, 633–637 (2008).

    Article  PubMed  CAS  Google Scholar 

  • Jean, W. C., Spellman, S. R., Nussbaum, E. S., and Low, W. C., Reperfusion injury after focal cerebral ischemia: The role of inflammation and the therapeutic horizon. Neurosurgery, 43, 1382–1396 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Jing, Y., The effect of QingKaiLing on the treatment of stroke. J. Beijing Univ. Chin. Med., 4, 77–79 (2001).

    Google Scholar 

  • Kim, Y. O., Leem, K., Park, J., Lee, P., Ahn, D. K., Lee, B. C., Park, H. K., Suk, K., Kim, S. Y., and Kim, H., Cytoprotective effect of Scutellariascutellarin baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia. J. Ethnopharmacol., 77, 183–188 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Kumari, M., Marmot, M., and Brunner, E., Social determinants of von willebrand factor: the Whitehall II study. Arterioscler. Thromb. Vasc. Biol., 20, 1842–1847 (2000).

    PubMed  CAS  Google Scholar 

  • Lavine, S. D., Hofman, F. M., and Zlokovic, B. V., Circulating antibody against tumor necrosis factor-alpha protects rat brain from reperfusin injury. J. Cereb. Blood Flow Metab., 18, 52–58 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Li, C.-Y., Pan, Y.-S., Jia, X., Li, K.-L., Liu, C.-M., Wang, X., and Li, P.-T., Effect of Huang qin (dried root of scutell-ariabaicalensis) and Zhizi (dried fruit of gardenia jasminoides) used in combination on ischemic cascade reaction in the rat model of focal cerebral ischemia and reperfusion. J. Beijing Univ. Chin. Med., 25, 31–33 (2002).

    CAS  Google Scholar 

  • Longa, E. Z., Weinstein, P. R., Carlson, S., and Cummins, R., Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke, 20, 84–91 (1989).

    PubMed  CAS  Google Scholar 

  • Ma, Q. C., Ma, J. S., and Sun, N. L., Clinical observation on effect of intervention therapy with anticoagulant in treating patients of hypertension complicated with acute ischemic cerebrovascular disease. Chin. J. Integ. Trad. Western Med., 21, 257–259 (2001).

    CAS  Google Scholar 

  • Nawashiro, H., Tasaki, K., Ruetzler, C. A., and Hallenbeck, J. M., TNF-alpha pretreatment induces protective effects against focal cerebral ischemia in mice. J. Cereb. Blood Flow Metab., 17, 483–490 (1997a).

    Article  PubMed  CAS  Google Scholar 

  • Nawashiro, H., Martin, D., and Hallenbeck, J. M., Neuroprotective effects of TNF binding protein in focal cerebral ischemia. Brain Res., 778, 265–271 (1997b).

    Article  PubMed  CAS  Google Scholar 

  • Ran, X., Liang, Q., Luo, G., Liu, Q., Pan, Y., Wang, B., and Pang, C. Simultaneous determination of geniposide, baicalin, cholic acid and hyodeoxycholic acid in rat serum for the pharmacokinetic investigations by high performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci., 842, 22–27 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Schaarschmidt, H., Prange, H. W., and Reiber, H., Neuronspecific enolase concentrations in blood as a prognostic parameter in cerebrovascular diseases. Stroke, 25, 558–565 (1994).

    PubMed  CAS  Google Scholar 

  • Tang, Y-H., Zhang, S-P., Liang, Y., and Deng, C-Q., Effects of Panax notoginseng saponins on mRNA expressions of interleukin-1β, its correlative factors and cysteinyl-aspartate specific protease after cerebral ischemia-reperfusion in rats. J. Chin. Integ. Med., 5, 328–332 (2007).

    Article  CAS  Google Scholar 

  • Tartaglia, L. A., Ayres, T. M., Wong, G. H., and Goeddel, D. V., A novel domain within the 55 kd TNF receptor signals cell death. Cell, 74, 845–853 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Tasaki, K., Ruetzler, C. A., Ohtsuki, T., Martin, D., Nawashiro, H., and Hallenbeck, J. M., Lipopolysaccharide pre-treatment induces resistance against subsequent focal cerebral ischemic damage in spontaneously hypertensive rats. Brain Res., 748, 267–270 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Uno, H., Matsuyama, T., Akita, H., Nishimura, H., and Sugita, M., Induction of tumor necrosis factor-alpha in the mouse hippocampus following transient forebrain ischemia. J. Cereb. Blood Flow Metab., 17, 491–499 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Wang, C. X. and Shuaib, A., Involvement of inflammatory cytokines in central nervous system injury. Prog. Neurobiol., 67, 161–172 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Ware, C. F., VanArsdale, S., and VanArsdale, T. L., Apoptosis mediated by the TNF-related cytokine and receptor families. J. Cell Biochem., 60, 47–55 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Williams, A. J., Berti, R., Dave, J. R., Elliot, P. J., Adams, J., and Tortella, F. C., Delayed treatment of ischemia/reperfusion brain injury: extended therapeutic window with the proteosome inhibitor MLN519. Stroke, 35, 1186–1191 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Yang, G.-Y., Liu, X.-H., Kadoya, C., Zhao, Y.-J., Mao, Y., Davidson, B. L., and Betz, A. L., Attenuation of ischemic inflammatory response in mouse brain using an adenoviral vector to induce overexpression of interleukin-1 receptor antagonist. J. Cereb. Blood Flow Metab., 18, 840–847 (1998a).

    Article  PubMed  CAS  Google Scholar 

  • Yang, G.-Y., Gong, C., Qin, Z., Ye, W., Mao, Y., and Bertz A. L. Inhibition of TNF-alpha attenuates infarct volume and ICAM-1 expression in ischemic mouse brain. Neuroreport, 9, 2131–2134 (1998b).

    Article  PubMed  CAS  Google Scholar 

  • Zhang, F. and Li, X-H., The influence of total saponion of panax notoginseng on the expression of TNF-α in rats with focal cerebral ischemia and reperfusion. Chin. J. Integ. Med. Cardio/Cerebrovas. Dis., 5, 597–599 (2007).

    Google Scholar 

  • Zhang, Y., Zhang, X., Park, T. S., and Gidday, J. M., Cerebral endothelial cell apoptosis after ischemia-reperfusion: role of PARP activation and AIF translocation. J. Cereb. Blood Flow Metab., 25, 868–877 (2005).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peng-tao Li.

Additional information

These two authors contribute equally to the paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hua, Q., Zhu, Xl., Li, Pt. et al. The inhibitory effects of cholalic acid and hyodeoxycholalic acid on the expression of TNFα and IL-1β after cerebral ischemia in rats. Arch. Pharm. Res. 32, 65–73 (2009). https://doi.org/10.1007/s12272-009-1119-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-009-1119-z

Key words

Navigation