Abstract
Pterostilbene (PTE), a natural dimethylated analog of resveratrol, possesses numerous health-beneficial properties. The ability of PTE to cross the blood–brain barrier raised the possibility that this compound may modulate central nervous system functions, including seizure activity. The aim of our study was to investigate the activity of PTE in the larval zebrafish pentylenetetrazole (PTZ) seizure assay and three acute seizure tests in mice, i.e., in the maximal electroshock seizure threshold (MEST), 6 Hz-induced psychomotor seizure threshold and intravenous (iv) PTZ tests. Additionally, potential antidepressant activity of PTE was estimated in the forced swim test in mice. The chimney test was used to determine the influence of PTE on motor coordination in mice, while its influence on neuromuscular strength was assessed in the grip strength test in mice. Locomotor activity was determined to verify the results from the forced swim test. PTE revealed an evident anticonvulsant effect both in zebrafish larvae (10 µM; 2 h-incubation) and mice (at doses of 100 and 200 mg/kg, intraperitoneally) but it did not exhibit antidepressant potential in the forced swim test. Furthermore, it did not cause any statistically significant changes in motor coordination, neuromuscular strength and locomotor activity in mice. In conclusion, our present findings demonstrate for the first time the anticonvulsant potential of PTE. The aforementioned results suggest that it might be employed in epilepsy treatment, however, further precise studies are required to verify its activity in other experimental seizure and epilepsy models and its precise mechanism of action should be determined.
Highlights
Epilepsy is a common chronic disorder which affects about 65 million people worldwide [1]
Epidemiological studies revealed that 9–37% patients with epilepsy suffer from depression and prevalence of depression is even higher in people with drugresistant epilepsy [3]
Exposure to PTE significantly reduced both number (Fig. 2a, two-way analysis of variance (ANOVA): F(1,28) = 9.76, p = 0.0041) and total duration (Fig. 2b, two-way ANOVA: F(1,28) = 32.36, p < 0.0001) of epileptiform discharges in the zebrafish brain in comparison to the control group which was incubated in the vehicle
Summary
Epilepsy is a common chronic disorder which affects about 65 million people worldwide [1]. It is characterized by recurrent seizures which result from excessive and synchronous electrical activity of some groups of neurons in the central nervous system [1]. Since the introduction of the first antiepileptic drug—bromide, in 1857, nearly 40 antiepileptic agents have been entered into the pharmaceutical market. Despite high availability of antiepileptic medication approximately 30% of patients with epilepsy do not achieve satisfying effects of pharmacological treatment due to continued seizures and/or unacceptable side effects [2]. Epidemiological studies revealed that 9–37% patients with epilepsy suffer from depression and prevalence of depression is even higher in people with drugresistant epilepsy [3]. There is a need to search new drugs with better efficacy and safety profile to treat patients with epileptic disorders alone and concomitant depression
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