(-)-Epigallocatechin-3-Gallate Protects Against Lithium-Pilocarpine-Induced Epilepsy by Inhibiting the Toll-Like Receptor 4 (TLR4)/Nuclear Factor-κB (NF-κB) Signaling Pathway

Med Sci Monit. 2019 Mar 7:25:1749-1758. doi: 10.12659/MSM.915025.

Abstract

BACKGROUND Temporal lobe epilepsy (TLE) is the most common type of intractable epilepsy in humans, and it is often accompanied by cognitive impairment. In this study, we examined the effects of (-)-Epigallocatechin-3-gallate (EGCG) after SE on behavior in the rat lithium-pilocarpine model of TLE. MATERIAL AND METHODS The rats were randomly divided into 3 groups: (1) the control group, in which 12 rats received no treatment); (2) the epilepsy (EP) group, in which 15 rats were treated with saline after status epilepticus (SE); and (3) the EP+EGCG group, in which 15 rats were treated with EGCG (25 mg/kg/d, intraperitoneal) after SE. The SE model was induced with lithium chloride-pilocarpine, and electroencephalography and a high-definition camera were used to monitor SRS. The Morris water maze test and hippocampal late-phase long-term potentiation (L-LTP) recordings were used to evaluate cognitive impairment, and TLR4, NF-kappaB, and IL-1ß levels were determined using Western blot analysis. RESULTS We concluded that EGCG treatment after SE (1) markedly reduced SRS frequency in pilocarpine-treated rats, (2) improved epilepsy-induced cognitive impairment and reversed epilepsy-induced synaptic dysfunction in L-LTP in vivo, (3) protected hippocampal neurons from damage after SRS, and (4) significantly attenuated the increase in TRL-4 and IL-1ß hippocampal levels. The above findings clearly show that EGCG exerts antiepileptogenesis and neuroprotective effects on pilocarpine-induced epilepsy. CONCLUSIONS We found that EGCG can suppress seizures and inhibit hippocampal neuronal apoptosis, as well as improving cognitive function of epileptic rats. Our findings suggest that EGCG may a novel adjuvant therapeutic approach in epilepsy by improving epileptic behavior and cognitive dysfunction.

MeSH terms

  • Animals
  • Catechin / analogs & derivatives*
  • Catechin / metabolism
  • Catechin / pharmacology
  • Disease Models, Animal
  • Epilepsy / drug therapy*
  • Epilepsy / metabolism
  • Epilepsy / physiopathology*
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / physiopathology
  • Hippocampus / metabolism
  • Lithium
  • Long-Term Potentiation / drug effects
  • Male
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Pilocarpine
  • Rats
  • Rats, Sprague-Dawley
  • Seizures / physiopathology
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / drug effects
  • Toll-Like Receptor 4 / metabolism

Substances

  • NF-kappa B
  • Neuroprotective Agents
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Pilocarpine
  • Catechin
  • Lithium
  • epigallocatechin gallate