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Front Pharmacol. 2016 Jul 25;7:224. doi: 10.3389/fphar.2016.00224. eCollection 2016.

Protective Effects of Otophylloside N on Pentylenetetrazol-Induced Neuronal Injury In vitro and In vivo.

Frontiers in pharmacology

Feiya Sheng, Mengting Chen, Yuan Tan, Cheng Xiang, Mi Zhang, Baocai Li, Huanxing Su, Chengwei He, Jianbo Wan, Peng Li

Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau Macau, China.
  2. Faculty of Life Science and Technology, Kunming University of Science and Technology Kunming, China.

PMID: 27504096 PMCID: PMC4959150 DOI: 10.3389/fphar.2016.00224

Abstract

Approximately 30% of epileptic patients worldwide are medically unable to control their seizures. In addition, repeated epileptic seizures generally lead to neural damage. Pentylenetetrazol (PTZ) is a clinical circulatory and respiratory stimulant that is experimentally used to mimic epileptic convulsion in epilepsy research. Here, we systematically explore the neuroprotective effects of a pure compound isolated from Cynanchum otophyllum Schneid (Qingyangshen), Otophylloside N (OtoN), against PTZ-induced neuronal injury. We used three models: in vitro primary cortical neurons, in vivo mice, and in vivo zebrafish. Our results revealed that OtoN treatment may attenuate PTZ-induced morphology changes, cell death, LDH efflux in embryonic neuronal cells of C57BL/6J mice, and convulsive behavior in zebrafish. Additionally, our Western blot and RT-PCR results demonstrated that OtoN may attenuate PTZ-induced apoptosis and neuronal activation in neuronal cells, mice, and zebrafish. OtoN may reduce PTZ-induced cleavage of poly ADP-ribose polymerase and upregulation of the Bax/Bcl-2 ratio and decrease the expression level of c-Fos. This study is the first investigation of the neuroprotective effects of OtoN, which might be developed as a novel antiepileptic drug.

Keywords: Cynanchum otophyllum Schneid; apoptosis; epilepsy; neuroprotective effect; otophylloside N; pentylenetetrazol

References

  1. J Comp Physiol B. 2008 Jan;178(1):77-92 - PubMed
  2. Epilepsy Behav. 2015 Apr;45:53-63 - PubMed
  3. Epilepsy Behav. 2010 Jul;18(3):207-10 - PubMed
  4. Neurosci Lett. 2006 Jan 9;392(1-2):145-9 - PubMed
  5. Neurosci Res. 2012 Jan;72(1):1-8 - PubMed
  6. Neurochem Res. 2012 Aug;37(8):1670-80 - PubMed
  7. J Neurosci. 1998 Oct 15;18(20):8382-93 - PubMed
  8. Adv Exp Med Biol. 2014;813:109-22 - PubMed
  9. J Tradit Chin Med. 1996 Mar;16(1):48-50 - PubMed
  10. Neurotoxicol Teratol. 2014 Nov-Dec;46:18-25 - PubMed
  11. Epilepsia. 2005 Apr;46(4):470-2 - PubMed
  12. Sci Sin B. 1986 Mar;29(3):295-301 - PubMed
  13. PLoS One. 2012;7(11):e50694 - PubMed
  14. PLoS One. 2013;8(1):e54166 - PubMed
  15. J Neurosci. 1997 Dec 15;17(24):9746-50 - PubMed
  16. Mol Brain. 2009 Jun 22;2:20 - PubMed
  17. Brain Res. 2015 Dec 2;1628(Pt A):157-73 - PubMed
  18. BMC Neurosci. 2006 Dec 01;7:78 - PubMed
  19. Pak J Pharm Sci. 2015 Jan;28(1 Suppl):319-24 - PubMed
  20. Epilepsia. 2014 Jan;55(1):3-16 - PubMed
  21. Sci Rep. 2014 Jul 17;4:5715 - PubMed
  22. Prog Brain Res. 2002;135:111-9 - PubMed
  23. Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):12096-101 - PubMed
  24. Behav Brain Res. 2011 Aug 1;221(1):75-82 - PubMed
  25. Epilepsy Res. 2002 Jun;50(1-2):21-32 - PubMed
  26. Neuropharmacology. 2009 Jun;56(8):1124-30 - PubMed
  27. Neuroscience. 2005;131(3):759-68 - PubMed
  28. PLoS One. 2014 Oct 13;9(10):e109091 - PubMed
  29. Curr Med Chem Anticancer Agents. 2005 Jan;5(1):65-71 - PubMed
  30. Nat Rev Drug Discov. 2013 Oct;12(10):757-76 - PubMed
  31. Aquat Toxicol. 2009 Jun 4;93(1):29-36 - PubMed
  32. Science. 1988 Jun 3;240(4857):1328-31 - PubMed
  33. Neurosci Lett. 2015 Jul 10;599:125-8 - PubMed
  34. Neurochem Int. 2008 May;52(6):1100-5 - PubMed
  35. Neuroscience. 2015 May 7;293:55-66 - PubMed
  36. Free Radic Biol Med. 2015 Jul;84:331-43 - PubMed
  37. Expert Opin Ther Targets. 2013 Apr;17 (4):461-72 - PubMed

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