Skip to main content

Advertisement

Log in

Antioxidant effect of salvianolic acid B on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objetive

To investigate the neuroprotective effects and underlying mechanisms of salvianolic acid B (Sal B) extracted from Salvia miltiorrhiza on hippocampal CA1 neurons in mice with cerebral ischemia reperfusion injury.

Methods

Forty male National Institute of Health (NIH) mice were randomly divided into 4 groups with 10 animals each, including the sham group, the model group, the SalB group (SalB 22.5 mg/kg) and the nimodipine (Nim) group (Nim 1 mg/kg). A mouse model of cerebral ischemia and reperfusion injury was established by bilateral carotid artery occlusion for 30 min followed by 24-h reperfusion. The malondialdehyde (MDA) content, the nitric oxide synthase (NOS) activity, the superoxide dismutase (SOD) activity and total antioxidant capability (T-AOC) of the pallium were determined by biochemistry methods. The morphologic changes and Bcl-2 and Bax protein expression in hippocampal CA1 neurons were observed by using hematoxylineosin staining and immunohistochemistry staining, respectively.

Results

In the SalB group, the MDA content and the NOS activity of the pallium in cerebral ischemia-reperfusion mice significantly decreased and the SOD activity and the T-AOC significantly increased, as compared with the model group (P<0.05 or P<0.01). The SalB treatment also rescued neuronal loss (P<0.01) in the hippocampal CA1 region, strongly promoted Bcl-2 protein expression (P<0.01) and inhibited Bax protein expression (P<0.05).

Conclusions

SalB increases the level of antioxidant substances and decreases free radicals production. Moreover, it also improves Bcl-2 expression and reduces Bax expression. SalB may exert the neuroprotective effect through mitochondria-dependent pathway on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury and suggested that SalB represents a promising candidate for the prevention and treatment of ischemic cerebrovascular disease.

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

References

  1. Taoufik E, Probert L. Ischemic neuronal damage. Curr Pharm Des 2008;14:3565᾿573.

    Article  CAS  PubMed  Google Scholar 

  2. Yu YM, Kim JB, Lee KW, Kim SY, Han PL, Lee JK. Inhibition of the cerebral ischemic injury by ethyl pyruvate with a wide therapeutic window. Stroke 2005;36:2238᾿243.

    Article  CAS  PubMed  Google Scholar 

  3. Maeda M, Furuichi Y, Ueyama N, Moriquchi A, Satoh N, Matsuoka N, et al. A combined treatment with tacrolimus (fk506) and recombinant tissue plasminogen activator for thrombotic focal cerebral ischemia in rats: increased neuroprotective efficacy and extended therapeutic time window. J Cereb Blood Flow Metab 2002;22:1205᾿211.

    Article  CAS  PubMed  Google Scholar 

  4. Hu P, Luo GA, Zhao ZZ, Jiang ZH. Quality assessment of Radix salviae miltiorrhizae. Chem Pharm Bull 2005;53:481᾿86.

    Article  CAS  PubMed  Google Scholar 

  5. Du GH, Qiu Y, Zhang JT. Salvianolic acid B protects the memory functions against transient cerebral ischemia in mice. J Asian Nat Prod Res 2000;2:145᾿52.

    Article  CAS  PubMed  Google Scholar 

  6. Wang Y, Jiang YF, Huang QF, Ge GL, Cui W. Neuroprotective effects of salvianolic acid B against oxygen-glucose deprivation/reperfusion damage in primary rat cortical neurons. Chin Med J 2010;123:3612᾿619.

    CAS  PubMed  Google Scholar 

  7. Tang M, Feng WH, Zhang Y, Zhong J, Zhang J. Salvianolic acid B improves motor function after cerebral ischemia in rats. Beav Pharmacol 2006;17:493᾿98.

    CAS  Google Scholar 

  8. Jiang YF, Wang QH, Liu ZQ, Wang Q, Cai DY, Liu SJ, et al. Effects of salvianolic acid B on cerebral energy charge and activity of ATPase in mice with cerebral ischemia. China J Chin Mater Med (Chin) 2007;32:1903᾿906.

    CAS  Google Scholar 

  9. Jiang YF, Luo XC, Wang XM, Fang L, Hang QF. Effect of salvianolic acid B on mitochondrial function of cerebral ischemia in mice. Tsinghua Sci Technol 2009;14:528᾿33.

    Article  CAS  Google Scholar 

  10. Liu SJ, Jiang YF, Wang XM, Liu ZQ, Cai DY, Wang WR, et al. Effects of salvianolic acid B on the secretion of endothelial cells in mice with cerebral ischemia reperfusion. J Beijing Univ Tradit Chin Med (Chin) 2008;31:456᾿59.

    CAS  Google Scholar 

  11. Salles FJ, Strickland S. Localization and regulation of the tissue plasminogen activator-plasmin system in the hippocampus. J Neurosci 2002;22:2125᾿134.

    CAS  PubMed  Google Scholar 

  12. Shi H, Liu KJ. Cerebral tissue oxygenation and oxidative brain injury during ischemia and reperfusion. Front Biosci 2007;12:1318᾿328.

    Article  CAS  PubMed  Google Scholar 

  13. Jiang YF, Pan YS, Huang QF, Yan YB, Luo XC, Zhang RQ. The effect of herbs on cerebral energy metabolism in cerebral ischemia reperfusion mice. Chin Med J 2001;114:881᾿83.

    CAS  PubMed  Google Scholar 

  14. Chan PH. Role of oxidants in ischemic brain damage stroke. Stroke 1996;27:1124᾿129.

    Article  CAS  PubMed  Google Scholar 

  15. Drummond JC, McKay LD, Cole DJ, Patel PM. The role of nitric oxide synthase inhibition in the adverse effects of etomidate in the setting of focal cerebral ischemia in rats. Anesth Analg 2005;100:841᾿46.

    Article  CAS  PubMed  Google Scholar 

  16. Burda J, Matiasová M, Gottlieb M, Danielisová V, Námethová M, Garcia L, et al. Evidence for a role of second pathophysiological stress in prevention of delayed neuronal death in the hippocampal CA1 region. Neurochem Res 2005;30:1397᾿405.

    Article  CAS  PubMed  Google Scholar 

  17. Du J, Zhu YJ, Chen X, Fei Z, Yang S, Yuan W, et al. Protective effect of bone morphogenetic protein-6 on neurons from H2O2 injury. Brain Res 2007;1163:10᾿0.

    Article  CAS  PubMed  Google Scholar 

  18. Chao DT, Korsmeyer SJ. Bcl-2 family: regulators of cell death. Annu Rev Immunol 1998;16:395᾿19.

    Article  CAS  PubMed  Google Scholar 

  19. Levine B, Sinha S, Kroemer G. Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 2008;4:600᾿06.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Tsukahara S, Yamamoto S, Tin-Tin-Win-Shwe, Ahmed S, Kunuqita N, Arashidani K, et al. Inhalation of low-level formaldehyde increases the Bcl-2/Bax expression ratio in the hippocampus of immunologically sensitized mice. Neuroimmunomodulation 2006;13:63᾿8.

    Article  CAS  PubMed  Google Scholar 

  21. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35:495᾿16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Kuwana T, Newmeyer DD. Bcl-2-family proteins and the role of mitochondriain apoptosis. Curr Opin Cell Biol 2003;15:691᾿99.

    Article  CAS  PubMed  Google Scholar 

  23. Brookes PS, Yoon Y, Robotham JL, Anders MW, Sheu SS. Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am J Physiol Cell Physiol 2004;287:c817–c833.

    Article  CAS  PubMed  Google Scholar 

  24. Papa L, Gomes E, Rockwell P. Reactive oxygen species induced by proteasome inhibition in neuronal cells mediate mitochondrial dysfunction and a caspase-independent cell death. Apoptosis 2007;12:1389᾿405.

    Article  CAS  PubMed  Google Scholar 

  25. Crompton M. On the involvement of mitochondrial intermembrane junctional complexes in apoptosis. Curr Med Chem 2003;10:1473᾿484.

    Article  CAS  PubMed  Google Scholar 

  26. Honda HM, Korge P, Weiss JN. Mitochondria and ischemia/reperfusion injury. Ann N Y Acad Sci 2005;1047:248᾿58.

    Article  CAS  PubMed  Google Scholar 

  27. Vempati UD, Diaz F, Barrientos A, Narisara S, Mian AM, Millán JL, et al. Role of cytochrome C in apoptosis: increased sensitivity to tumor necrosis factor alpha is associated with respiratory defects but not with lack of cytochrome C release. Mol Cell Biol 2007;27:1771᾿783.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Szewczyk A, Wojtczak L. Mitochondria as a pharmacological target. Pharmacol Rev 2002;54:101᾿27.

    Article  CAS  PubMed  Google Scholar 

  29. Dluzniewska J, Beresewicz M, Wojewódzka U, Gajkowska B, Zablocka B. Transient cerebral ischemia induces delayed proapoptotic Bad translocation to mitochondria in CA1 sector of hippocampus. Brain Res Mol Brain Res 2005;133:274᾿80.

    Article  CAS  PubMed  Google Scholar 

  30. Li X, NemotoM, Xu Z, Yu SW, Shimoji M, Andrabi SA. Influence of duration of focal cerebral ischemia and neuronal nitric oxide synthase on translocation of apoptosis-inducing factor to the nucleus. Neuroscience 2007;144:56᾿5.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Sobrado M, López MG, Carceller F, García AG, Roda JM. Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase bcl-2 expression after focal cerebral ischemia. Neuroscience 2003;118:107᾿31.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yu-feng Jiang  (蒋玉凤).

Additional information

Supported by the National Natural Science Foundation of China (No. 30472281)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, Yf., Liu, Zq., Cui, W. et al. Antioxidant effect of salvianolic acid B on hippocampal CA1 neurons in mice with cerebral ischemia and reperfusion injury. Chin. J. Integr. Med. 21, 516–522 (2015). https://doi.org/10.1007/s11655-014-1791-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-014-1791-1

Keywords

Navigation