1. Academic Validation
  2. Rhein attenuates PTZ‑induced epilepsy and exerts neuroprotective activity via inhibition of the TLR4-NFκB signaling pathway

Rhein attenuates PTZ‑induced epilepsy and exerts neuroprotective activity via inhibition of the TLR4-NFκB signaling pathway

  • Neurosci Lett. 2021 Jul 27;758:136002. doi: 10.1016/j.neulet.2021.136002.
Lei Yu 1 Jiping Yang 2 Wei Yu 1 Jian Cao 1 Xueping Li 3
Affiliations

Affiliations

  • 1 Department of Basic Medicine, Xi'an Medical University, Xi'an, Shaanxi, China.
  • 2 Institute of Basic Medical Sciences, Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an, Shaanxi, China.
  • 3 Department of Basic Medicine, Xi'an Medical University, Xi'an, Shaanxi, China. Electronic address: [email protected].
Abstract

Background: Epilepsy is a common Neurological Disease that cannot be well controlled by existing antiepileptic drugs. Studies have implicated oxidative stress and inflammation in the pathophysiology of epilepsy. Rhein has a comprehensive pharmacological function in reducing inflammation and can play a neuroprotective role in many neurological diseases, however little is known about its effects on epilepsy.

Methods: A model of acute epilepsy in mice was established using the Pentylenetetrazol (PTZ) ignition method to evaluate the effects of Rhein on the duration and latency of convulsions, and the number and severity of seizures. Modified Neurological Severity Score (mNSS), Rotarod and open-field behavioral task tests were performed to evaluate the neuroprotective effect of Rhein. TUNEL staining was used to assess neuronal damage, and western blot, qPCR and ELISA kits were utilized to determine the expression of inflammatory signaling protein molecules and levels of inflammatory cytokines.

Results: In this study, we demonstrate that Rhein delayed the onset of seizures, decreased their severity, and reduced the duration and frequency of seizures in PTZ-induced epileptic mice. Furthermore, we found that Rhein blocked neurological deficits induced by PTZ. In addition, our results show that Rhein inhibited the activation of the TLR4-NFκB signaling pathway and decreased the secretion of the inflammatory cytokines TNF-α, IL-6, IL-1β, and IL-18.

Conclusion: Our results suggest that the anticonvulsant and neuroprotective effects of Rhein are achieved by disrupting the processes involved in PTZ acquisition of epilepsy.

Keywords

Epilepsy; Inflammation; Neuroprotection; Oxidative stress; TLR4-NFκB signaling.

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