Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid
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 incre...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222013270 |
| _version_ | 1811221120948371456 |
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| author | Ling Yang Tung-Hu Tsai |
| author_facet | Ling Yang Tung-Hu Tsai |
| author_sort | Ling Yang |
| collection | DOAJ |
| description | 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 bloodbrain 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. |
| first_indexed | 2024-04-12T07:53:48Z |
| format | Article |
| id | doaj.art-d9efe5d491dc4d3a964a653de980803a |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T07:53:48Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-d9efe5d491dc4d3a964a653de980803a2022-12-22T03:41:33ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113938Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acidLing Yang0Tung-Hu Tsai1Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, TaiwanInstitute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung 404, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Correspondence to: Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung University, 155, Li-Nong Street Section 2, Taipei 112, Taiwan.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 bloodbrain 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.http://www.sciencedirect.com/science/article/pii/S0753332222013270Gastrodia elata extractValproic acidPilocarpine-induced epileptic rat modelMicrodialysisHerb-drug pharmacokinetic interactionHerb-drug pharmacodynamic interaction |
| spellingShingle | Ling Yang Tung-Hu Tsai Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid Biomedicine & Pharmacotherapy Gastrodia elata extract Valproic acid Pilocarpine-induced epileptic rat model Microdialysis Herb-drug pharmacokinetic interaction Herb-drug pharmacodynamic interaction |
| title | Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid |
| title_full | Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid |
| title_fullStr | Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid |
| title_full_unstemmed | Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid |
| title_short | Neuroprotective effect and herbal-drug pharmacokinetic interaction of Gastrodia elata extract on valproic acid |
| title_sort | neuroprotective effect and herbal drug pharmacokinetic interaction of gastrodia elata extract on valproic acid |
| topic | Gastrodia elata extract Valproic acid Pilocarpine-induced epileptic rat model Microdialysis Herb-drug pharmacokinetic interaction Herb-drug pharmacodynamic interaction |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222013270 |
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