The effect of curcumin on epilepsy: an experimental review

Almost 70 million people worldwide are affected by epilepsy and its consequences (1). Epilepsy is commonly observed in two ranges of younger ages and above 60 years (2). Despite administration of the routine antiepileptic drugs (AEDs), nearly 30% of the seizures are resistant to antiepileptic drugs called drug resistant epilepsy (DRE) (3). Since the treatment may result in consequences of multi-drugs administration, interactions and side effects or sometimes invasive surgical methods in DRE, herbal treatment can be a good alternative choice due to its easy accessibility, lower cost and fewer side effects. Different medicinal plants have been recommended due to their antiepileptic effects including Rosa Damascena, Citrus aurantium L, Chaihu-longu-muli-tang, Thymoquinone, Zhenxianling, Nigella Sativa (4-7). Turmeric derived from the rhizome of Curcuma Longa is an Indian dietary spice, which has been used as a herbal remedy in Ayurveda (Indian traditional medicine). Recently, there has been an upward trend in active compounds of turmeric called curcuminoids, which the major compounds is curcumin (Diferuloyl Methane) making 90% of the curcuminoid content of the original spice (8,9). Its beneficial properties have been known as anti-inflammatory, and anti-oxidant, as well as supportive effects in chemotherapy (10). Its positive effects have been reported on various diseases and conditions including topically administration in wounds, blistering diseases like pemphigus and herpes zoster, acne and skin infections, oral administration in common cold, liver diseases, urinary tract diseases, diabetes, Alzheimer’s disease, epilepsy, cognitive disorders and various cancers, and also via inhalation in chronic rhinitis and coryza (11-14). One of the suggested mechanisms of curcumin effects is decreasing inflammatory cytokines (15), which are known to play a dominant role in epilepsy pathophysiology (16). Epigenetic mechanism through regulating miRNA expressions is another pathway, which explains the long-term antiepileptic effect of this beneficial medicine (17). Recent emphasis on the use of natural and complementary medicine in western societies has drawn the interest of scientific community to this remedy.
In this literature, we have reviewed the available trial researches, which studied specifically antiepileptic effect of curcumin.

Literature Review
In recent years, there has been an upward trend in researching the administration of herbal medicine as adjuvant therapy in chronic diseases including epilepsy. Due to the cultural aspects in Iran, this trend has been well accepted by the patients. Although turmeric has been one of a very commonly used dietary spice and traditional herbal remedies, its derivation as a newly introduced medicine-curcumin has not been used to a large extent. Therefore, it was an area for investigation the beneficial properties, molecular mechanisms, safety of use, effective dose, administration route and possible adverse effects to make the medicine fully known and introduced to be used in every condition it might have a positive outcome. However, as in trials the antiepileptic effect has been studied only in animal models, this is one step toward the clinical human study.
The mentioned animal studies’ different details are summarized in Tables 1. As the first executive step, 8 out of 17 studies induced seizures by pentylenetetrazole (PTZ) kindling, 3 by kainic-acid, 3 by pilocarpine and 4 trials worked with side effect related to curcumin was reported between the ranges of administration doses 40 to 300 mg/kg orally or 50 to 200 mg/kg intraperitoneal. All the studies’ outcomes supported the anticonvulsant effect of curcumin in different dose and different administration rout except one which showed oral administration has no effect on chronic seizure, possibly because it did not reach the brain at adequate effect levels (34). As curcumin makes a fine adjuvant therapy for epilepsy, some researchers investigated its interactions with the currently used AEDs. Said and Noor confirmed that curcumin definitely reduced the adverse effects caused by some AEDs by reducing the dose of AEDs(21,26). Reeta and Anovadiya reported that the adjuvant therapy make it possible to gradually decrease the dose of AEDs while obtaining the same positive clinical outcome (23,27). Although the synergistic effect of curcumin was found and presented by Anovadiya, Said research showed no such effect (21,27).

Conclusion
Epilepsy is one of the worldwide important diseases, which both the seizure frequency and the treatment with AEDs affect the quality of life of patients and many suffer from the consequences. Herbal medicine has been presented to be a safe adjuvant therapy with lower cost and better outcome. Curcumin- the major extract of turmeric- has found to have antiepileptic effect according to recent investigations. It has been demonstrated to be safe in animal studies in a number of species. But, it has to be mentioned that the metabolism of curcumin between human and rats is different and humans can tolerate higher doses of this medicine without significant side effects. It not only has no critical adverse effect, but also can protect patients from other AEDs severe side effects and hopefully it makes it possible to gradually decrease the dose of AEDs in long-term combination therapy. This article reviewed animal studies from 2008 up to now studying the antiepileptic effect of curcumin in order to take a step toward the clinical human study in future.

Conflict of Interest
The authors declare no conflict of interest.