Anticonvulsant activity of Fumaria schleicheri dry extract and sodium valproate: Role of neurotrophin and cytokine pathways

Abstract

Introduction: Cytokine and neurotrophin pathways can be potential targets for principally new anticonvulsant drugs which in perspective will be probably able to solve the problem of pharmacological resistance for people sick with epilepsy and to avoid polypragmasy which considerably increases the risk of developing side effects. Objective: The role of neurotrophin and cytokine link in anticonvulsant activity of Fumaria schleicheri Soy.-Will. dry extract and sodium valproate was assessed by the change in the cerebral level of NGF and IL-1β, TNF-α, IL-4. Materials and Methods: A total of 51 mice were used. The animals were divided into 4 groups: intact control, pentylenetetrazole, pentylenetetrazole + F. schleicheri dry extract, pentylenetetrazole + sodium valproate. F. schleicheri dry extract (100 mg/kg) and sodium valproate (300 mg/kg) were administered into the stomach once a day for 3 days. Pentylenetetrazole (80 mg/kg) was administered subcutaneously on the 3rd day for 30 minutes after the introduction of the tested drugs. After 18 hours the content of cerebral NGF and neurotropic cytokines was determined in the surviving animals. Results: Both F. schleicheri dry extract and sodium valproate provide an expressed anticonvulsant activity, resulting in a significant increase in the latency of the first seizure and reducing the number of clonic-tonic convulsions in 1 mouse, % of mice with tonic seizures and the duration of the convulsive period in the group. Pentylenetetrazole causes considerable changes in both neurotrophin NGF, and cytokines with the proved neurotropic properties – IL-1β, TNF-α и IL-4. F. schleicheri dry extract as sodium valproate, decreased pentylenetetrazole-associated NGF overexpression, normalized the content of IL-1β, TNF-α and increased the level of IL-4 compared not only with the group of animals that were getting pentylenetetrazole, but also compared with intact control. The significant correlation relationship was marked only in the seizure control between TNF-α and IL-4. Conclusion: Thus, the experimental evidence supports a role of NGF and IL-1β, TNF-α and IL-4 on anticonvulsant activity of F. schleicheri dry extract and sodium valproate and suggests potential targets for perspective anticonvulsant drugs.