IMR Press / JIN / Volume 21 / Issue 1 / DOI: 10.31083/j.jin2101021
Open Access Original Research
Effects of Stevia rebaudiana Bertoni extracts in the rat model of epilepsy induced by pentylenetetrazol: Sirt-1, at the crossroads between inflammation and apoptosis
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1 Department of Anatomy, College of Medicine, King Khalid University, 61421 Abha, Saudi Arabia
2 Department of Histology and Cell Biology, Faculty of Medicine, Benha University, 13518 Benha, Egypt
3 Department of Medical Physiology, Faculty of Medicine, Mansoura University, 35516 Mansoura, Egypt
4 Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, 61421 Abha, Saudi Arabia
5 Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, 21955 Makah, Saudi Arabia
*Correspondence:; (Abdelaziz M. Hussein)
J. Integr. Neurosci. 2022, 21(1), 21;
Submitted: 23 June 2021 | Revised: 5 September 2021 | Accepted: 7 September 2021 | Published: 28 January 2022
(This article belongs to the Special Issue Non-medication treatment for medically intractable epilepsy)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

The current study investigated the effects of stevia extracts on a PTZ-induced epileptic rat model and its potential mechanism. Thirty male Sprague-Dawley rats were equally subdivided into 3 groups; (1) normal control (NC) group, (2) PTZ-group: received PTZ (50 mg/kg, i.p. every other day) for 2 weeks, and (3) PTZ+ Stevia group: received PTZ and stevia (200 mg/kg orally daily) for 4 weeks (2 weeks before the start of PTZ treatment and 2 weeks with PTZ administration). The first jerk latency and the seizure score were assessed in rats. Also, brain tissue samples were collected by the end of the experiment, and oxidative stress markers (catalase, MDA, and total antioxidant capacity (TAC)) were measured by biochemical analysis in hippocampal brain homogenates. Also, in the hippocampus, the expression of IL6 and Bcl-2 at the mRNA level and expression of Sirt-1, P53, caspase-3, GFAP, and NF-kB in CA3 hippocampal region by immunohistochemistry was investigated. PTZ substantially increased the seizure score and decreased the seizure latency. Also, PTZ significantly increased MDA, GFAP, IL-6, NF-kB, caspase-3, and p53 and significantly reduced Sirt-1, TAC, and Bcl-2 in hippocampal tissues compared to the control group (p < 0.01). However, Stevia Rebaudiana Bertoni (Stevia R.) significantly attenuated the PTZ-induced seizures, improved oxidative stress markers, downregulated GFAP, IL-6, NF-kB, caspase-3, and p53, and upregulated Sirt-1 and Bcl-2 in the CA3 hippocampal region (p < 0.01). In conclusion, Stevia R. exhibits neuroprotective and antiepileptic actions in PTZ-induced epilepsy due to its antioxidant, anti-apoptotic, and anti-inflammatory effects. Additionally, the Sirt-1 pathway might be involved in the antiepileptic and neuroprotective effects of stevia in PTZ-kindled epileptic rat model.

Oxidative stress
Fig. 1.
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