Effects of Stevia rebaudiana Bertoni extracts in the rat model of epilepsy induced by pentylenetetrazol: Sirt-1, at the crossroads between inflammation and apoptosis

Abstract

The current study investigated the e fects of stevia extracts on a PTZinduced 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-in lammatory e fects. Additionally, the Sirt-1 pathway might be involved in the antiepileptic and neuroprotective e fects of stevia in PTZ-kindled epileptic rat model.

Understanding the molecular mechanisms of Acori Tatarinowii Rhizoma: Nardostahyos Radix et Rhizoma in epilepsy treatment using network pharmacology and molecular docking

“…Studies on seizures during EP have shown an up-regulation of TP53 and CASP3 in the brain; genetic elimination or pharmacologic suppression of TP53 can alleviate seizure-induced cell apoptosis. [38] BPs enriched through GO analysis include responses to oxidative stress, neuronal death, regulation of the extrinsic apoptotic signaling pathway, and postsynaptic signal transduction. The KEGG enrichment analysis indicates that the signaling pathways of ATR-NRR intervention in EP are mainly related to oxidative stress, inflammation, programmed cell death pathways, including the PI3K-Akt, IL-17, TNF, and apoptosis signaling pathways.…”

“…Studies on seizures during EP have shown an up-regulation of TP53 and CASP3 in the brain; genetic elimination or pharmacologic suppression of TP53 can alleviate seizure-induced cell apoptosis. [ 38 ]…”

Antioxidant Activity of Leaf Extracts from Stevia rebaudiana Bertoni Exerts Attenuating Effect on Diseased Experimental Rats: A Systematic Review and Meta-Analysis

“…The ferric reducing antioxidant power (FRAP) assay [40] is based on the ability of antioxidants to reduce ferric ion Fe +3 to ferrous ion Fe +2 in a redox reaction, the Fe +2 then reacts with the colorimetric reagent TPTZ (2,4,6-tripyridyl-s-triazine, and iron(III) chloride hexahydrate) to produce a complex which can be measured spectrophotometrically at 593 nm. In one study [41], TAC was indirectly measured by determining the residual H 2 O 2 through the conversion of 3,5, dichloro dicloro-2-hydroxy benzensulphonate to a colored product. The measurement of this colored product can be measured spectrophotometrically at 500-510 nm.…”

“…A thorough literature search for antioxidant activity of stevia resulted in 184 articles. After screening of titles and abstracts, and compliance with the PRISMA guidelines (http://www.prisma-statement.org/ (accessed on 26 January 2023)) (Figure 2), 22 articles were found to satisfy the eligibility criteria [41,42,44,45,[55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72]. Seventeen records were additionally retrieved from screening lists of references, and two of them [37,73] were enrolled in the meta-analysis, making a total of 24 articles, which contained 104 studies in total.…”

Cold Plasma-Induced Changes in Stevia rebaudiana Morphometric and Biochemical Parameter Correlations

“…SGs are gaining popularity as sweeteners due to their confirmed health benefits in vivo and in vitro. Besides the sweet taste, stevia extract and SGs demonstrate therapeutic benefits as a joint nutraceutical in the management of chronic diseases including overweight and obesity, diabetes mellitus, fatty liver, cardiac fibrosis, liver fibrosis, inflammatory bowel disease, certain types of cancer, hypertension, and chronic kidney diseases (reviewed in [4]), and they exhibit neuroprotective and antiepileptic activity [5]. SGs are gaining popularity as sweeteners due to their confirmed health benefi vivo and in vitro.…”