The ameliorative effects of sesamol against seizures, cognitive impairment and oxidative stress in the experimental model of epilepsy

Document Type : Original Article


1 Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Objective(s):A growing interest has recently been attracted towards the identification of plant-based medications including those with protective effects against cognitive impairment. Sesamol has shown promising antioxidant and neuroprotective effects, therefore, we aimed to evaluate its therapeutic potential in epilepsy which is commonly associated with oxidative stress and cognitive impairment.
Materials and Methods: Male Wistar rats received pentylenetetrazole (PTZ) (30 mg/kg, IP) once every other day until the development of kindling, i.e., the occurrence of stage 5 of seizures for three consecutive trials. After the completion of kindling procedure, behavioural tests including elevated plus maze and passive avoidance were performed in order to assess learning and memory. Oxidative stress was assessed by estimation of lipid peroxidation and reduced glutathione. The effects of pretreatment with sesamol (10, 20, and 30 mg/kg, IP) against PTZ-induced seizures, cognitive impairmentand oxidative stress were investigated.
Results: 32.45 ± 1.86 days after treatment with PTZ, kindling was developed that was associated with myoclonic jerks and generalized tonic-clonic seizures. Moreover, PTZ kindling induced a remarkable cognitive impairment and oxidative stress. Sesamol (30 mg/kg) significantly delayed the development of kindling and prevented seizure-induced cognitive impairment and oxidative stress.
Conclusion: Sesamol exerts ameliorative effects in the experimental model of epilepsy. This phytochemical may be considered as a beneficial adjuvant for antiepileptic drugs.  


1. Tapsell LC, Hemphill I, Cobiac L, Patch CS, Sullivan DR, Fenech M,et al. Health benefits of herbs and spices: the past, the present, the future. Med J Aust 2006; 185:S4–24.
2. Ahmad S, Yousuf S, Ishrat T, Khan MB, Bhatia K, Fazli IS,et al. Effect of dietary sesame oil as antioxidant on brain hippocampus of rat in focal cerebral ischemia. Life Sci 2006; 79:1921–1928.
3. Jeng KC, Hou RC, Wang JC, Ping LI. Sesamin inhibits lipopolysaccharide-induced cytokine production by suppression of p38 mitogen-activated protein kinase and nuclear factorkappaB. Immunol Lett 2005; 97:101–106.
4. Hsu DZ, Liu MY. Sesame oil attenuates multiple organ failure and increases survival rate during endotoxemia in rats. Crit Care Med 2002; 30:1859–1862.
5. Cheng FC, Jinn TR, Hou RCW. Neuroprotective effects of sesamin and sesamolin on gerbil brain in cerebral ischemia. Int J Biomed Sci 2006; 2:284–288.
6. Sharma S, Kaur IP. Development and evaluation of sesamol as an antiaging agent. Int J Dermatol 2005; 45:200–208.
7. Kapadia GJ, Azuine MA, Tokuda H, Takasaki M, Mukainaka T, Konoshima T,et al. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis. Pharmacol Res 2002; 45:499-505.
8. Kumar B, Kuhad A, Chopra K. Neuropharmaco-logical effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences. Psychopharmacology 2011; 214:819–828.
9. Hassanzadeh P, Hassanzadeh A. Implication of NGF and endocannabinoid signalling in the mechanism of action of sesamol: a multi-target natural compound with therapeutic potential. Psychopharmacology 2013; 229:571-578.
10. Chopra K, Tiwari V, Arora V, Kuhad A. Sesamol suppresses neuro-inflammatory cascade in experimental model of diabetic neuropathy. J Pain 2010; 11:950-957.
11. Vangilder RL, Kelly KA, Chua MD, Ptachcinski RL, Huber JD. Administration of sesamol improved blood-brain barrier function in streptozotocin-induced diabetic rats. Exp Brain Res 2009; 197:23-34.
12. Misra S, Tiwari V, Kuhad A, Chopra K. Modulation of nitrergic pathway by sesamol prevents cognitive deficits and associated biochemical alterations in intracerebroventricular streptozotocin administered rats. Eur J Pharmacol 2011; 659:177-186.
13. Kumar P, Kalonia H, Kumar A. Protective effect of sesamol against 3-nitropropionic acid-induced cognitive dysfunction and altered glutathione redox balance in rats. Basic Clin Pharmacol Toxicol 2010; 107:577-582.
14. Galano A, Alvarez-Idaboy JR, Francisco-Márquez M. Physicochemical insights on the free radical scavenging activity of sesamol: importance of the acid/base equilibrium. J Phys Chem B 2011; 115:13101-13109.
15. Sudha K, Rao AV, Rao A. Oxidative stress and antioxidants in epilepsy. Clin Chim Acta 2001; 303:19-24.
16. Chang BS, Lowenstein DH. Epilepsy. N Engl J Med 2003; 349:1257–1266.
17. Hartzfeld P, Elisevich K, Pace M, Smith B, Gutierrez JA. Characteristics and surgical outcomes for medial temporal post-traumatic epilepsy. Br J Neurosurg 2008; 22:224–230.
18. Cascino GD. Epilepsy: contemporary perspectives on evaluation and treatment. Mayo Clin Proc 1994; 69:1199–1211.
19. Shannon HE, Love PL. Effects of antiepileptic drugs on learning as assessed by a repeated acquisition of response sequences task in rats. Epilepsy Behav 2007; 10:16-25.
20. Morimoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus models of epilepsy: rewiring the brain. Prog Neurobiol 2004; 73:1-60.
21. Becker A, Grecksch G, Ruthrich HL, Pohle W, Marx B, Matthies H. Kindling and its consequences on learning in rats. Behav Neural Biol 1992; 57:37-43.
22. Rogawski MA, Kurzman PS, Yamaguchi S, Li H. Role of AMPA and GluR5 kainate receptors in the development and expression of amygdala kindling in the mouse. Neuropharmacology 2001; 40:28–35.
23. Chu PY, Srinivasan P, Deng JF, Liu MY. Sesamol attenuates oxidative stress-mediated experimental acute pancreatitis in rats. Hum Exp Toxicol 2012; 31:397–404.
24. Malhotra J, Gupta YK. Effect of adenosine receptors modulation on pentylenetetrazole-induced seizures in rats. Br J Pharmacol 1997; 120:282-288.
25. Reddy DS, Kulkarni SK. Possible role of nitric oxide in the nootropic and antiamnesic effects of neurosteroids on aging- and dizocilpine-induced learning impairment. Brain Res 1998; 799:215-229.
26. Hlinak Z, Krejci I. MK-801 induced amnesia for the elevated plus-maze in mice. Behav Brain Res 2002; 131:221-225.
27. Altman HJ, Stone WS, Ogren SO. Evidence for a possible functional interaction between serotonergic and cholinergic mechanisms in memory retrieval. Behav Neural Biol 1987; 48:49-62.
28. Monleón S, Urquiza A, Arenas MC, Vinader-Caerols C, Parra A. Chronic administration of fluoxetine impairs inhibitory avoidance in male but not female mice. Behav Brain Res 2002; 136:483-488.
29. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95:351-358.
30. Mori A, Yokoi I, Noda Y, Willmore LJ. Natural antioxidants may prevent post traumatic epilepsy: A Hassanzadeh et al Sesamol and experimental epilepsy proposal based on experimental animal studies. Acta Med Okayama 2004; 58:11-18.
31. Marsh ED, Brooks-Kayal AR, Porter BE. Seizures and antiepileptic drugs: does exposure alter normal brain development? Epilepsia 2006; 47:1999-2010.
32. Ramachandran S, Prasad NR. Sesamol modulates ultraviolet-B-induced apoptotic and inflammatory signalling in human skin dermal fibroblasts. Int J Nutr Pharmacol Neurol Dis 2012; 2:31-39.
33. Hsu DZ, Chien SP, Chen KT, Liu MY. The effect of sesamol on systemic oxidative stress and hepatic dysfunction in acutely iron-intoxicated mice. Shock 2007; 28:596-601.
34. Geetha T, Rohit B, Indu Pal K. Sesamol: An efficient antioxidant with potential therapeutic benefits. Med Chem 2009; 5:367-371.
35. Narasimhan R, Vaithiyanathan M, Janardanam V. Neuroprotective effect of sesamol in glioma induced in rats. Biomed Int 2011; 2:22-27.
36. Cavazos JE, Sutula TP. Progressive neuronal loss induced by kindling: a possible mechanism for mossy fiber synaptic reorganization and hippocampal sclerosis. Brain Res 1990; 527:1-6.
37. Rauca C, Zerbe R, Jantze H. Formation of free hydroxyl radicals after pentylenetetrazole-induced seizure and kindling. Brain Res 1999; 847:347-351.
38. Rocha L, Briones M, Ackermann RF, Anton B, Maidment NT, Evans CJ,et al. Pentylenetetrazole-induced kindling: early involvement of excitatory and inhibitory systems. Epilepsy Res 1996; 26:105-113.