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

Abstract

Antidepressant-like activity of T. kotschyanus has been recently reported by scientists but insufficient attention has been so far 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 GABA_A 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 GABA_A 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.

Keywords: Epilepsy; GABA-A receptors; Insomnia; Memory; Mice; Phenolic content; Thymus kotschyanuse.

Figure 1

Effect of T. kotschyanus on the percentage of open arms spent time in EPM test (A). Effect of T. kotschyanus on the percentage of central to peripheral zone spent time in OFT (B). Data are presented as mean ± SEM. * indicates p < 0.05 and *** indicates p < 0.001 compared to the control group; (n = 10) in all groups

Figure 2

Effect of T. kotschyanus on potentiation of pentobarbital sleeping time. Data are presented as mean ± SEM. ** indicates p < 0.01 compared to the control group; ## indicates p < 0.01 between two compared groups; (n = 10) in all groups

Figure 3

Effect of T. kotschyanus on avoidance latency in passive avoidance test. Data are presented as mean ± SEM. ‎*** indicates p < 0.001 ‎compared to the control group; (n = 10) in all groups

Figure 4

Effect of T. kotschyanus on the total distance movement of mice in the open field test after 30 min (A) and 24 h (B) of treatments. Data are presented as mean ± SEM. ** indicates p < 0.01 and ‎*** indicates p < 0.001 ‎compared to the control group; (n = 10) in all groups