Effect of Pterostilbene, a Natural Analog of Resveratrol, on the Activity of some Antiepileptic Drugs in the Acute Seizure Tests in Mice

Dorota Nieoczym,Piotr Wlaź,Katarzyna Socała,Piotr Jedziniak,Elżbieta Wyska

doi:10.1007/s12640-019-00021-1

Abstract

Pterostilbene (PTE), a natural analog of resveratrol, is available both as a diet ingredient and a dietary supplement. The present study was undertaken to assess the effect of PTE on the activity of antiepileptic drugs in the acute seizure tests in mice, i.e., the intravenous pentetrazole (iv PTZ) seizure threshold, maximal electroshock (MES), and 6 Hz-induced psychomotor seizure tests. Our study revealed that PTE enhanced the anticonvulsant effect of clonazepam but did not change the activity of tiagabine in the iv PTZ test. In the MES test, PTE increased the effect of carbamazepine but did not affect the protective properties of topiramate, while in the 6-Hz test, we noted a significant enhancement of the activity of oxcarbazepine, but there were no changes in the activity of valproate. Interactions of PTE with carbamazepine and oxcarbazepine were pharmacokinetic, which was determined by the increase of concentration of these antiepileptic drugs both in the serum and brain. In contrast, interactions between PTE and clonazepam were pharmacodynamic since there were no changes in the concentration of clonazepam. Combined treatment with carbamazepine and PTE significantly attenuated muscular strength (estimated in the grip strength test) but did not change motor coordination (assessed in the chimney test) in mice. Other studied antiepileptic drugs and their combinations with PTE did not change these parameters. Further studies are required to evaluate the influence of PTE on the activity of anticonvulsant drugs to estimate the safety of using PTE by patients with epilepsy.

Highlights

Pterostilbene (PTE, 3,5-dimethoxy-4′-hydroxystilbene) is a naturally occurring polyphenol in the stilbene group which was first isolated from red sandalwood and subsequently detected in grapes, blueberries, and heartwood
A statistically significant increase in tonic seizure thresholds in comparison to the control (5% Tween-treated) group was noted both in the group treated with CZP alone and groups injected with a combination of this antiepileptic drug with PTE
We showed the anticonvulsant activity of PTE in the zebrafish PTZ assay and three acute seizure threshold tests in mice, i.e., in the intravenous pentetrazole (iv PTZ), maximal electroshock seizure threshold (MEST), and 6 Hz psychomotor seizure tests (Nieoczym et al 2019)

Summary

Introduction

Pterostilbene (PTE, 3,5-dimethoxy-4′-hydroxystilbene) is a naturally occurring polyphenol in the stilbene group which was first isolated from red sandalwood and subsequently detected in grapes, blueberries, and heartwood. It was identified in some plants used in folk medicine for the treatment of diabetes and cardiovascular diseases (Kosuru et al 2016). Compared with RES, PTE has greater lipophilicity and higher bioavailability after oral administration, which makes it more clinically useful (Kapetanovic et al 2011) Both of these compounds produce numerous health beneficial effects, e.g., antioxidative, antiinflammatory, anticancer, and anti-obesity properties (Kosuru et al 2016). Clinical study did not show any negative drug effects on the hepatic, renal, and glucose markers (Riche et al 2013)

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