An In-Vivo Study on Anticonvulsant, Anxiolytic, and Sedative-Hypnotic Effects of the ‎Polyphenol-Rich Thymus Kotschyanus Extract; Evidence for the Involvement of GABA-A ‎Receptors

Document Type: Research article

Authors

1 Student Research Committee, Department of Pharmacology and Toxicology, School of Pharmacy, Shahid ‎Beheshti University of Medical Sciences, Tehran, Iran

2 Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran,Iran.

3 Food Safty Research Center, Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical ‎Sciences, Tehran, Iran

5 Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

6 Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Abstract

Antidepressant-like activity of T. kotschyanus has been recently reported by scientists but insufficient attention has ‎so far been devoted to T. kotschyanus, and there is a lack of information on the other neurobehavioral effects and ‎side effects of this species. In the current study, the anticonvulsant, anxiolytic and sedative-hypnotic, effects of ‎Thymus kotschyanus extract on male NMRI mice were evaluated using pentylenetetrazole, maximal electroshock, ‎elevated plus maze, and pentobarbital-induced sleeping tests. Since phenolic compounds and flavonoids have main ‎roles in pharmacological effects of most plant extracts, the phenolic and flavonoid contents of the extract were ‎measured with Folin-Ciocalteu and AlCl3 reagents. Acute toxicity, passive avoidance, and open field tests were ‎carried out to assess the toxicity of the extract. To find out the possible mechanism of action, flumazenil as the ‎specific GABAA receptor antagonist was used. Anticonvulsant and hypnotic effects of the extract were observed at ‎‎400 and 600 mg/kg. The extract at the dose of 200 mg/kg revealed significant anxiolytic effects, but it did not show ‎any adverse effects on learning and memory at all the tested doses. Results of this study indicate that Thymus ‎kotschyanus extract has anticonvulsant‎, anxiolytic and hypnotic effects, which are likely related to the ability of ‎some phenolic compounds to activate α1-containing GABAA receptors but more experiments still need to be carried ‎out in order to find the exact mechanism, active component, and the toxicity of the Thymus kotschyanus extract. ‎

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