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Chrysophanol attenuates cognitive impairment, neuroinflammation, and oxidative stress by TLR4/NFκB-Nrf2/HO-1 and BDNF/VEGF signaling in stress-intensified PTZ induced epilepsy in mice

  • 0Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Frontiers in Pharmacology +

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December 9, 2024

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December 9, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Chrysophanol, a natural compound, effectively reduced seizure activity and stress in a mouse model of epilepsy. This study highlights its neuroprotective potential by modulating key molecular pathways involved in seizure control and neuronal health.

Area Of Science

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background

  • Epilepsy is frequently comorbid with stress, which exacerbates seizures through neuronal circuit imbalance.
  • Key factors in epilepsy include dysregulated BDNF/VEGF, oxidative stress, neuroinflammation, and apoptosis.
  • Stress significantly impacts the pathophysiology and severity of epileptic seizures.

Purpose Of The Study

  • To evaluate the neuroprotective and antiepileptic effects of chrysophanol.
  • To investigate the underlying molecular pathways modulated by chrysophanol in a stress-exacerbated epilepsy model.
  • To assess chrysophanol's efficacy in mitigating seizures and stress-related symptoms.

Main Methods

  • Pentylenetetrazole (PTZ) was used to induce seizures in mice, combined with daily restraint stress.
  • Chrysophanol was administered at various doses (0.1, 1, 10 mg/kg) before PTZ administration.
  • Evaluations included behavioral tests, antioxidant assays, histopathology, immunohistochemistry, cortisol measurement (ELISA), and gene expression analysis (RT-PCR).

Main Results

  • Chrysophanol significantly reduced seizure intensity and frequency.
  • It enhanced antioxidant levels (GSH, GST, CAT) and decreased oxidative stress markers (MDA, Nitric oxide).
  • Treatment improved neuronal morphology, increased anti-apoptotic (BCL-2) and Nrf-2 expression, and decreased pro-apoptotic (BAX) expression.

Conclusions

  • Chrysophanol exhibits significant neuroprotective and antiepileptic properties at 10 mg/kg.
  • It effectively reverses stress-induced epilepsy by modulating TLR4/NFκB -Nrf2/HO-1 and BDNF/VEGF pathways.
  • Chrysophanol demonstrates therapeutic potential for managing epilepsy, particularly when stress is a contributing factor.

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