Abstract
It is necessary to seek more effective sources to design new drug against epilepsy. This study aimed to evaluate the effect of hydroalcoholic extract of Artemisia persica on pentylenetetrazole- (PTZ-) induced seizure in male mice by investigating the possible role of the NMDA receptor and antioxidative stress effect. The phenolic profile of A. persica extract was determined by HPLC-DAD analysis. Mice were treated with normal saline or A. persica extract or pentobarbital or a subeffective dose of extract plus ketamine (NMDA receptor antagonist) and/or effective dose of extract plus NMDA. PTZ (90 mg/kg) was injected intravenously for induction of seizure. The seizure threshold was measured. Then mice were euthanized and the antioxidant capacity and the level of malondialdehyde (MDA) of the prefrontal cortex and serum were measured. The gene expression of NMDA receptor subunits (Nr2a and Nr2b) was determined by real-time PCR. Findings showed that A. persica extract increased the seizure threshold, increased antioxidant capacity, and decreased MDA levels in the serum and brain samples. A. persica extract reduced the expression of NMDA receptor subunits. The result showed that ketamine potentiated the effect of the subeffective dose of extract. HPLC analysis showed that quercetin had the highest flavonoid content and also caffeic acid had the highest content of the phenolic acids. A. persica extract probably via NMDA receptor exerts anticonvulsant properties.
Highlights
Epilepsy is one of the most common chronic neurological disorders that affect a significant percentage of the world’s population [1]
It has been shown that PTZ increases intracellular calcium ion concentrations which are associated with N-methyl-d-aspartate (NMDA) receptors activation [6]
Flavonoids and phenolic acids were quantified by the HPLC method and compounds were identified and quantified as μg per 0.02 g of dried extract. e results are shown in Table 2. e flavonoid content of the extract was free of rutin and naringin
Summary
Epilepsy is one of the most common chronic neurological disorders that affect a significant percentage of the world’s population [1]. Previous studies have shown that activation of NMDA receptors induces oxidative stress in neurons [12,13,14]. Ample evidence demonstrated that mitochondrial dysfunction and oxidative stress play pivotal role in the pathophysiology of seizures In this concept, research studies determined that antioxidants exerted anticonvulsant properties [17,18,19]. In this study, considering (1) the incomplete effects of antiepileptic drugs in some patients as well as their side effects, (2) the involvement of NMDA receptors in the pathophysiology of seizures, and (3) the reported pharmacological effects for A. persica, we intend to investigate the anticonvulsant effect of hydroalcoholic extract of A. persica in PTZ-induced seizures in mice by considering the possible role of NMDA receptors
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