Control of Granule Cell Dispersion by Natural Materials Such as Eugenol and Naringin: A Potential Therapeutic Strategy Against Temporal Lobe Epilepsy

J Med Food. 2016 Aug;19(8):730-6. doi: 10.1089/jmf.2016.3712. Epub 2016 Jul 12.


The hippocampus is an important brain area where abnormal morphological characteristics are often observed in patients with temporal lobe epilepsy (TLE), typically showing the loss of the principal neurons in the CA1 and CA3 areas of the hippocampus. TLE is frequently associated with widening of the granule cell layer of the dentate gyrus (DG), termed granule cell dispersion (GCD), in the hippocampus, suggesting that the control of GCD with protection of hippocampal neurons may be useful for preventing and inhibiting epileptic seizures. We previously reported that eugenol (EUG), which is an essential component of medicinal herbs and has anticonvulsant activity, is beneficial for treating epilepsy through its ability to inhibit GCD via suppression of mammalian target of rapamycin complex 1 (mTORC1) activation in the hippocampal DG in a kainic acid (KA)-treated mouse model of epilepsy in vivo. In addition, we reported that naringin, a bioflavonoid in citrus fruits, could exert beneficial effects, such as antiautophagic stress and antineuroinflammation, in the KA mouse model of epilepsy, even though it was unclear whether naringin might also attenuate the seizure-induced morphological changes of GCD in the DG. Similar to the effects of EUG, we recently observed that naringin treatment significantly reduced KA-induced GCD and mTORC1 activation, which are both involved in epileptic seizures, in the hippocampus of mouse brain. Therefore, these observations suggest that the utilization of natural materials, which have beneficial properties such as inhibition of GCD formation and protection of hippocampal neurons, may be useful in developing a novel therapeutic agent against TLE.

Keywords: dentate gyrus; epilepsy; eugenol; granule cell dispersion; naringin.

Publication types

  • Review

MeSH terms

  • Animals
  • Citrus / chemistry
  • Dentate Gyrus / cytology
  • Dentate Gyrus / drug effects*
  • Epilepsy, Temporal Lobe / drug therapy*
  • Epilepsy, Temporal Lobe / metabolism
  • Epilepsy, Temporal Lobe / pathology
  • Eugenol / pharmacology
  • Eugenol / therapeutic use*
  • Flavanones / pharmacology
  • Flavanones / therapeutic use*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Syzygium / chemistry
  • TOR Serine-Threonine Kinases / metabolism


  • Flavanones
  • Multiprotein Complexes
  • Neuroprotective Agents
  • Plant Extracts
  • Eugenol
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • naringin