Neuro-Behavioral Profile and Toxicity of the Essential Oil of Dorema ammoniacum Gum as an Anti-seizure, Anti-nociceptive, and Hypnotic Agent with Memory-enhancing Properties in D-Galactose Induced Aging Mice

Abstract

In this study, we focused on the neuro-behavioral profile, toxicity, and possible mechanisms of action of Dorema ammoniacum gum essential oil (DAG-EO). For this purpose, passive avoidance and Y-maze tests were performed to evaluate the potential effect of DAG-EO in the attenuation of memory impairment induced by 49 days administration of D-galactose and acute injection of scopolamine. Anticonvulsant and anti-nociceptive activities of DAG-EO were evaluated in the pentylenetetrazole and ‎maximal electroshock-induced models of seizure and acetic acid-induced writhing tests, respectively. To find the possible mechanism of action, flumazenil and naloxone were used. Furthermore, the possible side effects were determined in the open field, grip strength, and ‎rotarod tests. Our findings supported that 7-day administration of DAG-EO (50 and 100 mg/kg) improves memory impairment induced following administration of D-galactose and scopolamine. It was also revealed that DAG-EO possesses a dose-dependent sedative-hypnotic (100 mg/kg), anticonvulsant (ED₅₀ ≈ 170 mg/kg), and anti-nociceptive (ED₅₀ ≈ 175 mg/kg) activities possibly mediated via directly and/or indirectly modulation of GABA_A and opioid receptors. No side effect was observed except muscle relaxation which was less than that of diazepam. The output of this study confirms anti-seizure, anti-nociceptive, sedative-hypnotic, and memory-enhancing properties of DAG-EO by modulation of GABA_A receptors.

Keywords: Dorema ammoniacum gum; Epilepsy; GABAA; Insomnia; Memory.

Figure 1

Effect of DAG-EO on avoidance latency in D-galactose-induced memory impairment. All values are expressed as mean ± SEM. ^‎‎***indicate p-value < 0.001, ^**indicates p-value < 0.01 ‎compared to the vehicle group, ^###indicates p-value < 0.001 in two defined groups‎; (n = 10) in each group

Figure 2

Effect of DAG-EO on avoidance latency in scopolamine-induced memory impairment. All values are expressed as mean ± SEM. ^‎**indicates p-value < 0.01 ‎compared to the vehicle group, ^###indicates p-value < 0.001 in two defined groups‎; (n = 10) in each group

Figure 3

Effect of DAG-EO on the percentage of spontaneous alternation ‎ in D-galactose-induced memory impairment. All values are expressed as mean ± SEM. ^‎***indicates p-value < 0.001 ‎compared to the vehicle group, ^#indicates p-value < 0.05 in two defined groups‎; (n = 10) in each group

Figure 4

Effect of DAG-EO on the total number of arm entries in the Y-maze test‎. All values are expressed as mean + SEM; (n = 10) in each group

Figure 5

Effect of DAG-EO on the locomotor activity of mice (A) one hour and (B) 24 h after the last administration of DAG-EO‎ in the open field test‎. All values are expressed as mean + SEM. (n = 10) in each group

Figure 6

Effect of DAG-EO on the sleeping time in Pentobarbital-induced sleep test. All values are expressed as mean + SEM. ^‎***indicates p-value < 0.001 ‎compared to the vehicle group, ^‎**indicates p-value < 0.01 ‎compared to the vehicle group, ns indicates no significant and ^##indicates p-value < 0.01 in two indicated groups; (n = 10) in each group

Figure 7

Effect of DAG-EO and diazepam on (A) the grip force and (B) the motor coordination of animals. All values are expressed as mean + SEM. ‎***indicates p < 0.001 ‎compared to the vehicle group, ‎**indicates p < 0.01 ‎compared to the vehicle group, ‎^{# # #}indicates p < 0.001 in the two ‎indicated groups; (n = 10) in each group