Curcumin offsets PTZ-induced epilepsy: involving inhibition of apoptosis, wnt/β-catenin, and autophagy pathways

Abstract

Curcumin is a natural antioxidant isolated from Curcuma longa that proved to protect against experimentally induced epilepsy in animals. In the current work, we aimed to explore the possible molecular mechanisms of curcumin neuroprotective effect on PTZ-induced epilepsy in rats. Thirty male Sprague Dawley rats were subdivided into three groups: (a) normal control group, (b) PTZ group: rats received PTZ (50 mg/kg i.p. every other day) for 14 days, (c) curcumin + PTZ group: received PTZ as in PTZ group in addition to curcumin (200 mg/kg per oral daily) for 14 days. After each PTZ injection, the seizure stage, time to the first seizure and the duration of seizures were recorded. Also, at the end of experiment, oxidative stress markers, the expression of splitted caspase-3, β-catenin, LC3 (marker of autophagy), and alpha synuclein proteins were measured in brain tissues. treatment with curcumin caused significant reduction in seizure score, increased time to the first seizure and shortened seizure duration. Also, curcumin caused a significant reduction in oxidative stress (decreased MDA level and increased GSH level) and a significant reduction in the expression of splitted caspase-3, β-catenin, LC3 and alpha synuclein proteins. These results suggest that curcumin has a neuroprotective effect that is not attributed only to its antioxidant activity, but it involves also suppression of PTZ-induced apoptosis, Wnt/β-catenin and autophagy pathways.

Anti-kindling effect of Ginkgo biloba leaf extract and L-carnitine in the pentylenetetrazol model of epilepsy

“…In the current study, a marked elevation in MDA levels was recorded in the hippocampus and hypothalamus in PTZ-kindled animals. This result is in accordance with the previous studies that showed lipid peroxidation increment in the brain during epileptic seizures (Alachkar et al 2020 ; Hamdy et al 2020 ).…”

“…In the present study, sequential injections of sub-convulsive dose of PTZ induced successively evoked chemical kindling in rats as evident from the seizure score. This finding agrees with previous studies carried out by Hamdy et al ( 2020 ) and Badawi et al ( 2021 ) who illustrated that the long-lasting seizure-evoked neuronal hyperactivity could result in an irreversible deleterious neurological change that finally ends by neuronal degeneration. The recurrence of seizures is associated with decreased numbers of GABA A receptor chloride channels, which attenuates GABA-dependent inhibition and/or activation of N-methyl-D-aspartate (NMDA) receptors (Ali et al 2004 ; Ceyhan et al 2005 ) and amplification in glutamate release (Rodrigues et al 2012 ).…”

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

“…PTZ-induced apoptosis is mediated by the activation of enzymes such as caspase-3, increased expression of apoptotic proteins such as p53, and decreased levels of anti-apoptotic Bcl-2 protein. The current study demonstrated a significant increase in caspase-3, p53 with a significant reduction in Bcl-2 in brain tissue of PTZtreated rats, which is in agreement with previous studies by Hussein et al [31] and Hamdy et al [32]. Moreover, Stevia R. exerted an anti-apoptotic action, as evidenced significant decline in caspase-3 and p53 with high expression of Bcl-2 with stevia-treated rats.…”

The standardized extract of Centella asiatica L. Urb attenuates the convulsant effect induced by lithium/pilocarpine without affecting biochemical and haematological parameters in rats

“…The treatment of epilepsy is mainly focused on the use of antiepileptic drugs (AEDs), which aim to prevent seizures and restore neuronal function. Special attention has been given to preclinical research on the antioxidant effects of natural compounds on neuronal function in various brain structures, such as the hippocampus, substantia nigra, and striatum [ 7 , 8 ]. For example, turmeric has been shown to reduce oxidative stress and the expression of proteins associated with apoptotic changes in the hippocampus of rats with pilocarpine-induced status epilepticus [ 8 ].…”

“…Special attention has been given to preclinical research on the antioxidant effects of natural compounds on neuronal function in various brain structures, such as the hippocampus, substantia nigra, and striatum [ 7 , 8 ]. For example, turmeric has been shown to reduce oxidative stress and the expression of proteins associated with apoptotic changes in the hippocampus of rats with pilocarpine-induced status epilepticus [ 8 ]. Centella asiatica administered to rats with parkinsonism showed a decrease in dopaminergic neuronal death in certain brain regions [ 7 ].…”