Effects of Hydro-ethanolic Extract of Tanacetum parthenium and its N-Butanol and Aqueous Fractions on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice

Dysfunction of membrane proteins including neurotransmitter receptors and ion channels followed by brain oxidative and nitrosative stress has been also demonstrated to involve in neuronal hyper-excitability.8,9 In addition, the elevated level of inflammatory cytokines such as interleukin (IL) 1ß in the brain has been reported to promote seizure activities.10 Electrical11 and chemical12 kindling are employed for induction of epileptic seizures in experimental models. PTZ as a GABAa receptors blocker has been shown to decrease the level of antioxidant indexes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) in cells of CA1 and CA3 areas of hippocampus in rats.15 Researchers also reported that the activation of glucagon like peptide 1 receptor (GLP1R) associated with inhibition of oxidative stress and up-regulation of heat shock proteinľO (Hsp70) in hippocampus of rats could exert the protective effects against PTZ-stimulated seizures.16 In addition, increased level of pro-inflammatory mediators such as IL-1ß, IL-6, IL-18 and tumor necrosis factor-a (TNF-a) was reported in rats kindled by PTZ.17 Tanacetumparthenium (TP), named feverfew, is a member from Asteraceae family which grows in different areas of the world such as Iran.18 Therapeutic effects including anti-inflammatory,19 anti-asthma,18 anti-fever,20 anti-migraine and anti-arthritis21 are attributed to this plant. Antioxidant ingredients such as sesquiterpene lactones, parthenolide, flavonoids and luteolin have been also identified in extract of TP.22,23 It has been documented that pre and post treatment with TP extract ameliorated hepatotoxicity followed by CCl4 injection via reduction of free radicals, modulation of antioxidant enzymes activity such as superoxide dismutase (SOD) and catalase (CAT) and suppression of lipid peroxidation in rats.24 Researchers showed that the quercetin present in TP extract has considerable protective effect on central nervous system.25 This substance derived from TP extract also could enhance slow waves sleep in rats.26 TP extract and its constituents have been also suggested to alleviate the headaches resulted from migraine through inhibition of nitric oxide production, suppression of serotonin release and reduction of Calcitonin Gene-Related Peptide (CGRP) secretion.27 Despite these lucrative properties, the anticonvulsant effect of TP has been not understood. [...]we designed this study to assess the effect of TP extract and its N