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    Novel effect of Arthrocen (avocado/soy unsaponifiables) on pentylenetetrazole-induced seizure threshold in mice: Role of GABAergic pathway

  • Golnaz Zamanian,1,* Ramin Goudarzi,2 Ahmadreza Dehpour,3
    1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
    2. Division of Research and Development, Pharmin USA, LLC, SanJose, California, USA.
    3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran


  • Introduction: Arthrocen, an avocado/soy unsaponifiable (ASU)-containing agent, is used in the clinic and it can decrease the pain of joint potentially. 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.
  • Methods: Acute administration of Arthrocen (10, 30, 75, 150 mg/kg) by oral gavage significantly (p < 0.01) increased the clonic seizure threshold induced by intravenous administration of PTZ.
  • Results: 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 demonstrated that Arthrocen could probably produce its anticonvulsant effect by enhancing GABAergic neurotransmission and/or action in the brain.
  • Conclusion: To conclude, the results of this study illustrate that Arthrocen had anticonvulsant property in PTZ-induced seizure threshold. This activity could not be reversed by NO inhibitor and NMDAR antagonist, but the GABA-A receptor antagonist could completely block the anticonvulsant effect of Arthrocen. Our findings reveal that GABA-A receptor may be contributing to the anticonvulsant effect of ASU.
  • Keywords: Arthrocen; GABA-A receptor; Nitric oxide synthase inhibitors; Pentylenetetrazol.