Ameliorative influence of Cnestis ferruginea vahl ex DC (Connaraceae) root extract on kainic acid-induced temporal lobe epilepsy in mice: Role of oxidative stress and neuroinflammation

J Ethnopharmacol. 2019 Oct 28:243:112117. doi: 10.1016/j.jep.2019.112117. Epub 2019 Jul 24.

Abstract

ETHNOPHARMACOLOGY RELEVANCE: the root decoction of Cnestis ferruginea Vahl ex DC (Connaraceae) is widely used in traditional African medicine for the treatment of various ailments including pain, inflammation and epilepsy. We have earlier reported anticonvulsant effect of Cnestis ferruginea root extract in mice.

Aim of the study: to evaluate the effect of ethanolic root extract of Cnestis ferruginea (CF) on kainic acid (KA)-induced temporal lobe epilepsy (TLE) in mice as well as the involvement of inflammatory mediators and oxidative stress.

Materials and methods: mice were randomly divided into preventive treatment (vehicle (normal saline) or CF (400 mg/kg, p.o.) for 3 consecutive days before KA (5 mg/kg, i.p.) on days 4 and 5. In the reversal model, KA (5 mg/kg, i.p.) was administered on days 1 and 2 before vehicle or CF (400 mg/kg) administration on days 3-5. The effect of treatments on seizure severity was recorded using Racine scale. Animals were euthanized on day 5, 6 h after last KA exposure in preventive model and 1 h after CF administration in reversal model to estimate markers of oxidative stress and neuroinflammation.

Results: exposure of mice to KA induced TLE evidenced in increased severity of seizures which was significantly reduced by the pre- and post-treatment of mice with CF. Moreso, KA-induced malondialdehyde/nitrite generation and GSH deficit in the brain were attenuated by CF treatments. KA-induced up-regulation of inflammatory transcription factors; cyclooxygenase-2 (COX-2) and nuclear facor-kappaB (NF-κB) in the CA1, CA2, CA3 and dentate gyrus (DG) regions of the hippocampus regions were attenuated by CF treatments.

Conclusion: findings from this study showed that Cnestis ferruginea root extract ameliorated KA-induced TLE through enhancement of antioxidant defense mechanism and attenuation of neuro-inflammatory transcription factors. Thus, could possibly be a potential phytotherapeutic agent in the management of temporal lobe epilepsy.

Keywords: COX-2; Hippocampus; NF-κB; Neuroinflammation; Oxidative stress.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Connaraceae*
  • Cyclooxygenase 2 / metabolism
  • Epilepsy, Temporal Lobe / chemically induced
  • Epilepsy, Temporal Lobe / drug therapy*
  • Epilepsy, Temporal Lobe / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Kainic Acid
  • Male
  • Medicine, African Traditional
  • Mice
  • NF-kappa B / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Plant Roots
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Seizures / metabolism

Substances

  • Anticonvulsants
  • NF-kappa B
  • Plant Extracts
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Kainic Acid