Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway

10.1016/j.jtcme.2019.11.005

Malihe Hassanzadeh；Niusha Sharifi；Shabnam Mahernia；Nastaran Rahimi；Ahmad Reza Dehpour；Massoud Amanlou

Onopordon acanthium ； Nitric oxide ； Nitric oxide synthase inhibitors ； Pentylenetetrazole ； Seizure ； Mice

Journal of Traditional and Complementary Medicine

11卷1期（2021 / 01 / 01）

22 - 26

英文

Epilepsy is identified as a brain disorder and characterized by unpredictable disruption of normal brain function. Due to adverse side effect associated with antiepileptic drugs and also resistance profile, improvement of antiepileptic medications with more beneficial anticonvulsant activity is essential. Natural products have demonstrated their therapeutic properties such as anxiolytic, antidepressant and anticonvulsant activities and a source for identification of novel lead compounds. Therefore, the purpose of this study was to evaluate the effects of Onopordon acanthium secondary metabolite, onopordia, on pentylenetetrazole (PTZ)-induced seizure in male mice and investigate the possible role of nitric oxide pathway. Different doses of onopordia (0.1, 1 and 10 mg/kg) and phenobarbital (20 mg/kg) were administered intraperitoneally (i.p., 30, 60 and 120 min) prior to induction of epileptic seizure and compared to control groups. Onopordia demonstrated anticonvulsant effects when administrated at dose of 10 mg/kg, i.p. and optimum time 60 min prior to induction of seizure. Anticonvulsant effect of onopordia was blocked by applying a single dose of a non-selective nitric oxide synthase (NOS) inhibitor, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME; 10 mg/kg, i.p.), and also a single dose of a selective neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI; 30 mg/kg, i.p.). Administration of ketamine as a N-Methyl-D-aspartic acid (NMDA) receptor antagonist (0.5 mg/kg; i.p.) with onopordia did not change the anticonvulsant effect of onopordia. The results of the present study demonstrated the anticonvulsant effect of onopordia as a new lead compound and also contribution of NO/nNOS pathway on PTZ-induced seizure in mice.

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