Abstract

Epilepsy is one of the most common neurological diseases, and current antiepileptic drugs fail to suppress seizure occurrence in around one third of epileptic patients. Curcumin is a phytochemical with promising effects on epilepsy treatment. However, its application has been hindered by its low bioavailability. In order to improve curcumin’s anti-seizure properties, increasing its bioavailability, here we proposed to micronize the compound through supercritical carbon dioxide processing, a suitable green chemistry technique to prepare and modify material properties. Here we investigated the anti-seizure potential of the classical antiepileptic drug valproate, curcumin in its natural state, and micronized curcumin in a PTZ-induced seizure model in zebrafish (Danio rerio). Concerning seizure development, valproate, curcumin and micronized curcumin showed protective effects, slowing seizure development both in larvae and adult animals. Nevertheless, considering the occurrence of the tonic-clonic seizure stage, only valproate and micronized curcumin reduced it, both in larvae and adult zebrafish, unlike non-processed curcumin. Our obtained results are very promising, since micronized curcumin showed effects that are similar to a classic antiepileptic drug, reducing seizure occurrence and slowing seizure progression.

Highlights

  • Epilepsy is one of the most common neurological diseases, affecting around 65 million people worldwide[1]

  • Curcumin has been extensively studied, and recently its promising therapeutic effect on epilepsy was evidenced[10,11,12]. This phytochemical did not prevent the occurrence of seizures, but weakened their severity and showed a protective effect against cognitive deficits in a temporal lobe epilepsy model induced by status epilepticus in rats[10]

  • Our obtained results are very promising, since micronized curcumin showed effects that are similar to a classic antiepileptic drugs (AEDs)

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Summary

Introduction

Epilepsy is one of the most common neurological diseases, affecting around 65 million people worldwide[1]. MTOR inhibition has been proposed as a potential antiepileptogenic and anticonvulsive strategy in several epilepsy and seizure animal models[6,7,8,9]. Curcumin has been extensively studied, and recently its promising therapeutic effect on epilepsy was evidenced[10,11,12]. This phytochemical did not prevent the occurrence of seizures, but weakened their severity and showed a protective effect against cognitive deficits in a temporal lobe epilepsy model induced by status epilepticus in rats[10]. Despite its promising therapeutic effect on reducing comorbidities associated to epilepsy, curcumin’s anticonvulsant potential is still poor. Supercritical carbon dioxide is a suitable green chemistry technique to www.nature.com/scientificreports/

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