Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 156, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113938
Keywords
Gastrodia elata extract; Valproic acid; Pilocarpine-induced epileptic rat model; Microdialysis; Herb-drug pharmacokinetic interaction; Herb-drug pharmacodynamic interaction
Funding
- Ministry of Science and Technology of Taiwan [MOST 111-2113-M-A49-018, MOST 110-2113-M-A49A-503, MOST 111-2321-B-A49-007]
- College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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The combination treatment of Gastrodia elata extract and valproic acid (VPA) can increase the VPA levels in the brain, enhance its antiepileptic effects, and exert synergistic anticonvulsive effects by protecting neurons and altering dopamine metabolite levels. This synergistic effect is mediated by transporters at the blood-brain barrier.
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 in-teractions 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.
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