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

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 esse...

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Main Authors: Malihe Hassanzadeh, Niusha Sharifi, Shabnam Mahernia, Nastaran Rahimi, Ahmad Reza Dehpour, Massoud Amanlou
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:Journal of Traditional and Complementary Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2225411018309003
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author Malihe Hassanzadeh
Niusha Sharifi
Shabnam Mahernia
Nastaran Rahimi
Ahmad Reza Dehpour
Massoud Amanlou
author_facet Malihe Hassanzadeh
Niusha Sharifi
Shabnam Mahernia
Nastaran Rahimi
Ahmad Reza Dehpour
Massoud Amanlou
author_sort Malihe Hassanzadeh
collection DOAJ
description 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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spelling doaj.art-bf25d06d312a400bb2561af338ad91dd2022-12-21T19:02:36ZengElsevierJournal of Traditional and Complementary Medicine2225-41102021-01-011112226Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathwayMalihe Hassanzadeh0Niusha Sharifi1Shabnam Mahernia2Nastaran Rahimi3Ahmad Reza Dehpour4Massoud Amanlou5Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranThe Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, IranExperimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranExperimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Corresponding author. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box: 14155-6451, Tehran, Iran. Tel.: +98 21 66959067; fax: +98 21 64121111.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.http://www.sciencedirect.com/science/article/pii/S2225411018309003Onopordon acanthiumNitric oxideNitric oxide synthase inhibitorsPentylenetetrazoleSeizureMice
spellingShingle Malihe Hassanzadeh
Niusha Sharifi
Shabnam Mahernia
Nastaran Rahimi
Ahmad Reza Dehpour
Massoud Amanlou
Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway
Journal of Traditional and Complementary Medicine
Onopordon acanthium
Nitric oxide
Nitric oxide synthase inhibitors
Pentylenetetrazole
Seizure
Mice
title Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway
title_full Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway
title_fullStr Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway
title_full_unstemmed Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway
title_short Effects of onopordia, a novel isolated compound from Onopordon acanthium, on pentylenetetrazole-induced seizures in mice: Possible involvement of nitric oxide pathway
title_sort effects of onopordia a novel isolated compound from onopordon acanthium on pentylenetetrazole induced seizures in mice possible involvement of nitric oxide pathway
topic Onopordon acanthium
Nitric oxide
Nitric oxide synthase inhibitors
Pentylenetetrazole
Seizure
Mice
url http://www.sciencedirect.com/science/article/pii/S2225411018309003
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