Jundishapur J Nat Pharm Prod. 2019 August; 14(3):e80039. Published online 2019 August 10. doi: 10.5812/jjnpp.80039. Research Article Ameliorative Effects of Ellagic Acid on Maximal Electroshock and Pentylenetetrazole-Induced Seizures in Mice Ahad Khazaei 1 , Seyyed Mohammad Taghi Mansouri 2 , Amir Siahpoosh 1, 3 , Behnam Ghorbanzadeh 4 , Saeed Salehi 5 and Mohammad Javad Khodayar 5, 6, * 1 Medicinal Plant Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 2 Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA 3 Department of Pharmacognosy, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 4 Department of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran 5 Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 6 Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran * Corresponding author: Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Email: jkhodayar@yahoo.com Received 2015 June 15; Revised 2018 June 01; Accepted 2018 September 29. Abstract Background: Epilepsy is a series of disorders in the central nervous system defined by disruption and abnormality in the electrical activity of the brain. The mechanisms of epilepsy occurrence are not fully determined and the current pharmacological therapeutics have low efficacy and are associated with adverse reactions due to narrow therapeutic indices. Ellagic acid has neuroprotective and antioxidant effects and increases the brain’s GABA levels. Objectives: This study was designed to evaluate the effects of ellagic acid on both maximal electroshock and pentylenetetrazole models of acute seizures in mice. Methods: Ellagic acid was administered at the doses of 25, 50, and 100 mg/kg in the two models of seizures. Results: The results showed that ellagic acid was effective at the lowest dose in the maximal electroshock-induced seizure in mice and the duration of hind limb tonic extension (HLTE) was significantly shorter in this group than in the untreated convulsive group. In the pentylenetetrazole convulsion model, ellagic acid significantly increased the latency to convulsion and Straub tail response. The latencies with ellagic acid were longer in groups treated with ellagic acid 25 mg/kg than with ellagic acid 50 and 100 mg/kg. Conclusions: In conclusion, it seems that ellagic acid has anticonvulsant effects in electroshock and pentylenetetrazole models of convulsion but its effects are attenuated or eliminated at higher doses. Keywords: Ellagic Acid, Pentylenetetrazole, Maximal Electroshock, Seizure, Mice 1. Background Epilepsy is the most common disorder of the central nervous system. It occurs due to the disruption of elec- trical activity, leading to acute and chronic changes in nerve function and mental abnormality (1). Epidemiologic studies show that 1% of people worldwide are affected by epilepsy and its prevalence is two to three times higher in African countries than in the rest of the world (2). In devel- oped countries, there are 4 to 10 people with epilepsy per 10000 population (3). There is a relationship between the epilepsy prevalence and age so that it is more common in the first 10 years of life, especially in the first year (4). The abnormal discharge of nerve cells by various factors such as low blood sugar, oxygen deficiency, and infection makes imbalance between excitatory and inhibitory systems in the brain and leads to convulsion and the loss of conscious- ness (5). In the last decade, plants have found an important role in clinical application as natural resources of phar- maceutical products. Nowadays different types of herbal medicines are commercially available in various dosage forms in the market (6). The World Health Organization es- timates that 80% of populations in Asian and African coun- tries use traditional medicine for the remedy of disease (7). Ellagitannins are hydrolyzable tannins that have functions in cell membranes (8). When ellagitannins are exposed to acid or base, the ester bond is hydrolyzed to form ellagic acid as a gallic acid dimer (Figure 1). Ellagic acid is found in plants such as pomegranate, walnut, strawberry, blueberry, eucalyptus, and oak (9). Be- cause of the key role of these compounds in the treatment of cancer and cardiovascular diseases, they are considered Copyright © 2019, Jundishapur Journal of Natural Pharmaceutical Products. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.