Skip to main content
Log in

Protective Effects of Nigranoic Acid on Cerebral Ischemia–Reperfusion Injury and its Mechanism Involving Apoptotic Signaling Pathway

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

The goal of this study was to assess the expression of poly ADP-ribose polymerase (PARP) and apoptosis-inducing factor (AIF) in the hippocampal CA1 region, and to find out whether nigranoic acid treatment exhibits protective effects on brain through PARP/AIF signaling pathway in cerebral ischemia–reperfusion animal model. Rats were randomly divided into three groups: Sham-surgery, ischemia–reperfusion, and nigranoic acid-treated. Rat models of middle cerebral artery occlusion were prepared using a way of thread occlusion. Rats in the nigranoic acid group were administered with 1 mg/kg intragastric nigranoic acid 6 and 2 h before brain ischemia, respectively. Following reperfusion, samples were collected at different time-points (6, 24, and 72 h) and each group was further divided into three subgroups. Apoptosis was measured using the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling method. The protein expression levels of AIF and PARP were detected using Western blot and AIF mRNA quantity was evaluated using the reverse transcription-polymerase chain reaction. Apoptosis, levels of AIF and PARP protein expression, and levels of AIF mRNA expression were significantly increased in the ischemia–reperfusion group compared with the sham-surgery group. However, apoptosis and the expression levels of AIF protein, PARP protein, and AIF mRNA at different time-points were significantly decreased in the nigranoic acid-treated group compared with the model group. We can judge that nigranoic acid has a strong protective effect on rat cerebral ischemia–reperfusion injury, and acts by downregulating nerve cell apoptosis by preventing the overactivation of PARP and AIF nuclear translocation.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Peng, Z. G., Xu, L. J., Ye, W. C., et al. (2010). Effective components against HIV-1 replicative enzymes isolated from plants. Yao Xue Xue Bao, 45, 235–240.

    CAS  PubMed  Google Scholar 

  2. Yuan, X. X., Yang, L. P., Yang, Z. L., et al. (2014). Effect of nigranoic acid on Ca(2)(+) influx and its downstream signal mechanism in NGF-differentiated PC12 cells. Journal of Ethnopharmacology, 153, 725–731.

    Article  CAS  PubMed  Google Scholar 

  3. Ba, X. H., Cai, L. P., & Han, W. (2014). Effect of cilostazol pretreatment on the PARP/AIF-mediated apoptotic pathway in rat cerebral ischemia-reperfusion models. Experimental Therapeutic Medicine, 7, 1209–1214.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Fabian, R. H., & Kent, T. A. (2012). Hyperglycemia accentuates persistent “functional uncoupling” of cerebral microvascular nitric oxide and superoxide following focal ischemia/reperfusion in rats. Translational Stroke Research, 3, 482–490.

    Article  CAS  PubMed  Google Scholar 

  5. Wen, P. Y., Yang, F. Z., Wang, F., et al. (2012). Study on regulation of tanshinone II(A) on GFAP and ATPase and PDI of cerebral ischemia reperfusion injury in rats. Zhong Yao Cai, 35, 1628–1632.

    CAS  PubMed  Google Scholar 

  6. Kumari, S., Anderson, L., Farmer, S., et al. (2012). Hyperglycemia alters mitochondrial fission and fusion proteins in mice subjected to cerebral ischemia and reperfusion. Translational Stroke Research, 3, 296–304.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Urbanski, H. F., Kohama, S. G., West, G. A., et al. (2012). Changes in spontaneous activity assessed by accelerometry correlate with extent of cerebral ischemia-reperfusion injury in the nonhuman primate. Translational Stroke Research, 3, 442–451.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Ahmad, A., Khan, M. M., Raza, S. S., et al. (2012). Ocimum sanctum attenuates oxidative damage and neurological deficits following focal cerebral ischemia/reperfusion injury in rats. Neurological Sciences, 33, 1239–1247.

    Article  PubMed  Google Scholar 

  9. Bruning, C. A., Prigol, M., Luchese, C., et al. (2012). Protective effect of diphenyl diselenide on ischemia and reperfusion-induced cerebral injury: involvement of oxidative stress and pro-inflammatory cytokines. Neurochemical Research, 37, 2249–2258.

    Article  PubMed  Google Scholar 

  10. Buch, P., Patel, V., Ranpariya, V., et al. (2012). Neuroprotective activity of Cymbopogon martinii against cerebral ischemia/reperfusion-induced oxidative stress in rats. Journal of Ethnopharmacology, 142, 35–40.

    Article  CAS  PubMed  Google Scholar 

  11. Chen, A., Lin, Z., Lan, L., et al. (2012). Electroacupuncture at the Quchi and Zusanli acupoints exerts neuroprotective role in cerebral ischemia-reperfusion injured rats via activation of the PI3 K/Akt pathway. International Journal of Molecular Medicine, 30, 791–796.

    CAS  PubMed  Google Scholar 

  12. Chen, S. H., Sun, H., Xu, H., et al. (2012). Effects of acupuncture of “Baihui”(GV 20) and “Zusanli”(ST 36) on expression of cerebral IL-1beta and TNF-alpha proteins in cerebral ischemia reperfusion injury rats. Zhen Ci Yan Jiu, 37, 470–475.

    CAS  PubMed  Google Scholar 

  13. Chen, Y., Wu, X., Yu, S., et al. (2012). Neuroprotective capabilities of Tanshinone IIA against cerebral ischemia/reperfusion injury via anti-apoptotic pathway in rats. Biological &/and Pharmaceutical Bulletin, 35, 164–170.

    Article  CAS  Google Scholar 

  14. Chen, Y., Wu, X., Yu, S., et al. (2012). Neuroprotection of tanshinone IIA against cerebral ischemia/reperfusion injury through inhibition of macrophage migration inhibitory factor in rats. PLoS ONE, 7, e40165.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Chong, Y., Wang, T., Wang, W., et al. (2012). Down-regulation of P-glycoprotein expression contributes to an increase in Danshensu accumulation in the cerebral ischemia/reperfusion brain. Mol Med Rep, 5, 812–816.

    CAS  PubMed  Google Scholar 

  16. Chu, K., Yin, B., Wang, J., et al. (2012). Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus. Journal of Neuroinflammation, 9, 69.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Cui, D., Wang, L., Qi, A., et al. (2012). Propofol prevents autophagic cell death following oxygen and glucose deprivation in PC12 cells and cerebral ischemia-reperfusion injury in rats. PLoS ONE, 7, e35324.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Culman, J., Nguyen-Ngoc, M., Glatz, T., et al. (2012). Treatment of rats with pioglitazone in the reperfusion phase of focal cerebral ischemia: a preclinical stroke trial. Experimental Neurology, 238, 243–253.

    Article  CAS  PubMed  Google Scholar 

  19. Dai, Q. X., Wang, L. L., & Chao, J. (2012). Effects of injecting adenosine A1 receptor agonist into baihui (GV20) on the cerebral cortex in ischemia/reperfusion injury model rats. Zhongguo Zhong Xi Yi Jie He Za Zhi, 32, 390–393.

    CAS  PubMed  Google Scholar 

  20. Di Domenico, F., Casalena, G., Jia, J., et al. (2012). Sex differences in brain proteomes of neuron-specific STAT3-null mice after cerebral ischemia/reperfusion. Journal of Neurochemistry, 121, 680–692.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Fan, T., Jiang, W. L., Zhu, J., et al. (2012). Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation. Biological &/and Pharmaceutical Bulletin, 35, 2004–2009.

    Article  CAS  Google Scholar 

  22. Gaur, V., & Kumar, A. (2012). Effect of nonselective and selective COX-2 inhibitors on memory dysfunction, glutathione system, and tumor necrosis factor alpha level against cerebral ischemia reperfusion injury. Drug and Chemical Toxicology, 35, 218–224.

    Article  CAS  PubMed  Google Scholar 

  23. Gong, W. H., Zheng, W. X., Wang, J., et al. (2012). Coexistence of hyperlipidemia and acute cerebral ischemia/reperfusion induces severe liver damage in a rat model. World Journal of Gastroenterology, 18, 4934–4943.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Gu, J. H., Ge, J. B., Li, M., et al. (2012). Inhibition of NF-kappaB activation is associated with anti-inflammatory and anti-apoptotic effects of Ginkgolide B in a mouse model of cerebral ischemia/reperfusion injury. European Journal of Pharmaceutical Sciences, 47, 652–660.

    Article  CAS  PubMed  Google Scholar 

  25. Gu, Y., Zheng, G., Xu, M., et al. (2012). Caveolin-1 regulates nitric oxide-mediated matrix metalloproteinases activity and blood-brain barrier permeability in focal cerebral ischemia and reperfusion injury. Journal of Neurochemistry, 120, 147–156.

    Article  CAS  PubMed  Google Scholar 

  26. Guo, C., Tong, L., Xi, M., et al. (2012). Neuroprotective effect of calycosin on cerebral ischemia and reperfusion injury in rats. Journal of Ethnopharmacology, 144, 768–774.

    Article  CAS  PubMed  Google Scholar 

  27. Guo, Y., & Chen, Z. W. (2012). Effect of total flavones of Rhododendra simsii on the activation of ERK induced by cerebral ischemia-reperfusion in rats. Zhong Yao Cai, 35, 1108–1111.

    CAS  PubMed  Google Scholar 

  28. Han, J. Q., Yu, K. Y., & He, M. (2012). Effects of puerarin on the neurocyte apoptosis and p-Akt (Ser473) expressions in rats with cerebral ischemia/reperfusion injury. Zhongguo Zhong Xi Yi Jie He Za Zhi, 32, 1069–1072.

    CAS  PubMed  Google Scholar 

  29. He, F., Qu, F., & Song, F. (2012). Aspirin upregulates the expression of neuregulin 1 and survivin after focal cerebral ischemia/reperfusion in rats. Experimental Therapeutic Medicine, 3, 613–616.

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Hu, J., Chai, Y., Wang, Y., et al. (2012). PI3 K p55gamma promoter activity enhancement is involved in the anti-apoptotic effect of berberine against cerebral ischemia-reperfusion. European Journal of Pharmacology, 674, 132–142.

    Article  CAS  PubMed  Google Scholar 

  31. Kovalska, M., Kovalska, L., Pavlikova, M., et al. (2012). Intracellular signaling MAPK pathway after cerebral ischemia-reperfusion injury. Neurochemical Research, 37, 1568–1577.

    Article  CAS  PubMed  Google Scholar 

  32. Kuang, G., He, Q., Zhang, Y., et al. (2012). Modulation of preactivation of ppar-beta on memory and learning dysfunction and inflammatory response in the hippocampus in rats exposed to global cerebral ischemia/reperfusion. PPAR Research, 2012, 209794.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tianda Feng.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, T., Liu, Y., Li, C. et al. Protective Effects of Nigranoic Acid on Cerebral Ischemia–Reperfusion Injury and its Mechanism Involving Apoptotic Signaling Pathway. Cell Biochem Biophys 71, 345–351 (2015). https://doi.org/10.1007/s12013-014-0204-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-0204-1

Keywords

Navigation