Anticonvulsant Effect of Swertiamarin Against Pilocarpine-Induced Seizures in Adult Male Mice

Neurochem Res. 2017 Nov;42(11):3103-3113. doi: 10.1007/s11064-017-2347-0. Epub 2017 Jul 5.

Abstract

Epilepsy is one of the common and major neurological disorders, approximately a third of the individuals with epilepsy suffer from seizures and not able to successfully respond to available medications. Current study was designed to investigate whether Swertiamarin (Swe) had anticonvulsant activity in the pilocarpine (PILO)-treated mice. Thirty minutes prior to the PILO (280 mg/kg) injection, the mice were administrated with Swe (50, 150, and 450 mg/kg) and valproate sodium (VPA, 200 mg/kg) once. Seizures and electroencephalography (EEG) were observed, and then the mice were killed for Nissl, Fluoro-jade B (FJB) staining. Astrocytic activation was examined in the hippocampus. Western blot analysis was used to examine the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). The results indicated that pretreatment with Swe (150, 450 mg/kg) and VPA (200 mg/kg) significantly delayed the onset of the first convulsion and reduced the incidence of status epilepticus and mortality. Analysis of EEG recordings demonstrated that Swe (150, 450 mg/kg) and VPA (200 mg/kg) sharply decreased epileptiform discharges. Furthermore, Nissl and FJB staining revealed that Swe (150, 450 mg/kg) and VPA (200 mg/kg) relieved the neuronal damage. Additionally, Swe (450 mg/kg) dramatically inhibited astrocytic activation. Western blot analysis showed that Swe (450 mg/kg) significantly decreased the expressions of IL-1β, IL-6, TNF-α and elevated the expression of IL-10. Taken together, these findings revealed that Swe exerted anticonvulsant effects on PILO-treated mice. Further studies are encouraged to investigate these beneficial effects of Swe as an adjuvant in epilepsy.

Keywords: Anti-inflammatory; Anticonvulsant; Astrocytes; Neuroprotective; Pilocarpine; Swertiamarin.

MeSH terms

  • Age Factors
  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Iridoid Glucosides / pharmacology
  • Iridoid Glucosides / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Pilocarpine / toxicity*
  • Pyrones / pharmacology
  • Pyrones / therapeutic use*
  • Seizures / chemically induced*
  • Seizures / physiopathology
  • Seizures / prevention & control*
  • Swertia*
  • Treatment Outcome

Substances

  • Anticonvulsants
  • Iridoid Glucosides
  • Pyrones
  • Pilocarpine
  • swertiamarin