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Novel Effect of Arthrocen (Avocado/Soy Unsaponifiables) on Pentylenetetrazole-Induced Seizure Threshold in Mice: Role of Gabaergic Pathway Publisher Pubmed



Goudarzi R1 ; Zamanian G2 ; Partoazar A3 ; Dehpour A2, 3
Authors
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Authors Affiliations
  1. 1. Division of Research and Development, Pharmin USA, LLC, SanJose, CA, United States
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Epilepsy and Behavior Published:2020


Abstract

Arthrocen, an avocado/soy unsaponifiable (ASU)-containing agent, is now used in the clinic and has potentially to decrease joint inflammation and pain associated with mild to severe osteoarthritis. Phytosterols are the major component of Arthrocen with documented anti-inflammatory properties, antioxidant, and analgesic effects. Here, we evaluated ASU anticonvulsant effect by its oral administration in pentylenetetrazole (PTZ)-induced seizure threshold and Maximal Electroshock Seizure (MES) Models. Also, the involvement of N-methyl-D-aspartate (NMDA) receptor, benzodiazepine receptor, and nitric oxide (NO) pathway were studied in anticonvulsant effect of ASU in male NMRI mice. Acute administration of Arthrocen (150, 75, 30, 10 mg/kg) by oral gavage significantly (p < 0.001) increased the clonic seizure threshold induced by intravenous administration of PTZ. Nonspecific inducible NO synthase (NOS) inhibitor L-NAME (10 mg/kg) and a specific NMDA receptor antagonist MK-801 (0.05 mg/kg) did not affect the anticonvulsant effect of Arthrocen, while pretreatment with flumazenil (0.25 mg/kg), a selective benzodiazepine receptor antagonist, reversed this effect (p < 0.01). Also, Arthrocen treated mice did not affect tonic hindlimb extension in the MES model. The data showed that Arthrocen might produce its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain. © 2019 Elsevier Inc.