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

• Main Authors: Feiya Sheng (Author), Mengting Chen (Author), Yuan Tan (Author), Cheng Xiang (Author), Mi Zhang (Author), Baocai Li (Author), Huanxing Su (Author), Chengwei He (Author), Jianbo Wan (Author), Peng Li (Author)
• Format: Book
• Published: Frontiers Media S.A., 2016-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2016.00224
• Keywords: Apoptosis; Epilepsy; pentylenetetrazol; Neuroprotective effect; Cynanchum otophyllum Schneid; Otophylloside N; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 7 (2016)

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.