Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid

Ling Yang, Tung Hu Tsai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Valproic acid (VPA) is a widely used antiepileptic drug, and the herbal extract of Gastrodia elata exerts an anticonvulsant effect. However, few studies have investigated the pharmacokinetic and pharmacodynamic interactions between G. elata extract and VPA. We hypothesize that G. elata extract increases the VPA levels in the brain and enhances the antiepileptic effects of VPA, and this synergistic effect is mediated by transporters at the blood–brain barrier (BBB). We performed microdialysis on pilocarpine-induced epileptic model rats in vivo to investigate this hypothesis. The results demonstrated that cotreatment with G. elata extract and VPA ameliorated drug-resistant epilepsy by increasing the VPA levels in the brain. In addition, G. elata extract and VPA exerted synergistic anticonvulsive effects to decrease the seizure severity by protecting neurons in the hippocampus and altering the DOPAC and 5-HT levels. However, these phenomena were partially blocked by the organic anion transporter peptide (OATP) inhibitor cyclosporine A (CsA; 20 mg/kg, i.p.), which demonstrated that the increase in the VPA level in the brain was modulated by the transporter OATP. This study provides a comprehensive strategy for assessing the interaction between traditional medicines and conventional antiepileptic drugs in a status epilepticus animal model.

Original languageEnglish
Article number113938
JournalBiomedicine and Pharmacotherapy
Volume156
DOIs
StatePublished - Dec 2022

Keywords

  • Gastrodia elata extract
  • Herb-drug pharmacodynamic interaction
  • Herb-drug pharmacokinetic interaction
  • Microdialysis
  • Pilocarpine-induced epileptic rat model
  • Valproic acid

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