Frontiers in Pharmacology (Jul 2016)

Protective effects of Otophylloside N on pentylenetetrazol-induced neuronal injury in vitro and in vivo

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

DOI
https://doi.org/10.3389/fphar.2016.00224
Journal volume & issue
Vol. 7

Abstract

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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 (PARP) 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.

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