Avicenna was the first person in medical history to use the term ‘epilepsy’, which means “being possessed by an outside force” in Latin. Ibn al-Nafis, a great Arab physician and scientist of his time, systematically described the symptoms and recovery of “head sick”, which is a synopsis of the Canon written 250 years earlier.

Avicenna assigned a chapter of the Canon to epilepsy under the title ‘Head and Brain Disorders’. From his point of view, there are two types of epilepsy: one that occurs suddenly and is over quickly, and one that is intense and continuous and may lead to death. In his opinion, epilepsy is a type of seizure which affects the brain.

Avicenna described symptoms of epilepsy as being weakness, forgetfulness, depression, nightmare, yellow tongue, tongue paresthesia, anger, and distress. He described an epileptic attack as follows: “The patient feels agitated and becomes unconscious, turns red, and stares with eyes distorted; respiration is impaired and the patient becomes cyanotic”. Muscle contractions, dizziness, salivation, and teeth gnashing are other symptoms and signs.

Avicenna theorized that the blockage of humors, especially phlegm and black bile, was a possible mechanism of epileptic convulsions. In the Canon, he classifies epilepsy based on age (children, adults) and the organ in which the attack starts (liver, stomach, spleen, or uterus). He explains that some precipitating factors (environmental temperature, direct solar radiation, bathing or training with a full stomach, overwhelming anger, fear or sorrow, and dyspepsia) provoke epileptic attacks.

Avicenna explains the general recommendation (to avoid excessive heat or cold, excess sexual intercourse, swimming, and postprandial exercise) and states that therapy is based on the specific condition of the patient.

Plant-based antiepileptic therapy constitutes a great part of the treatments described in the Canon and other Iranian traditional medicine references.

In the following section, the results of tests performed on 11 plants have been summarized; attention was focused on their anticonvulsant activity.

4.1. Paeonia officinalis L.

The root extract of P. officinalis (peony root) was identified as a potent in vitro inhibitor of neuron damage in the CA1 area of the hippocampus in rats. Data indicated that peony root extract has excellent protective effects on damaged neurons in addition to anticonvulsant action when administered orally.

4.2. Bryonia alba L.

Ethanolic extract of the aerial parts of B. alba showed moderate affinity to the benzodiazepine-site of the GABA receptor. The GABAA-benzodiazepine site is a primary target in the treatment of epilepsy that enhances the sensitivity of the GABAA receptor for endogenous GABA. After binding GABA to the receptor, the cell is inhibited and an anticonvulsant activity is achieved. Conversely, administration of the aqueous extracts showed no affinity for the GABA–benzodiazepine receptors.

4.3. Ferula persica Willd.

The effects of ethanol extract of the aerial parts of F. persica on epilepsy have been evaluated in mice. Results indicated that a dose of 300 mg/kg (i.p.) of ethanol extracts cannot prevent pentylenetetrazole (PTZ)-induced seizures; therefore, it does not possess anticonvulsant effects compared with the untreated animals at the used dose.

4.4. Lavandula stoechas L.

The effects of the aqueous-methanolic extract of L. stoechas flowers on epilepsy and spasm were evaluated in mice. Results showed that treatment with 600 mg/kg of extract significantly delayed first seizure onset, reduced convulsion severity, and prolonged the onset of lethality induced by PTZ. A prolongation in the time of sodium pentobarbital-induced hypnosis was also observed. Possible explanations of these results might be the role plant extract plays as a calcium channel blocker.

4.5. Ferula asafoetida L.

Bagheri et al. showed that the oleo-gum-resin of F. assafoetida (300 mg/kg, i.p.) could not prevent PTZ-induced seizures in mice. The latency of hind limb tonic extension was obtained within 2–3 min, and the percentage of mice mortality was 100% in the PTZ test. In the mentioned study, it was proposed that F. assafoetida could not prevent PTZ-induced seizure.

4.6. Coriandrum sativum L.

The aqueous and ethanolic seed extracts of C. sativum were investigated for their possible anticonvulsant effects using PTZ and (maximal electro shock) MES tests. The results indicated that both extracts have an anticonvulsant effect, and the maximum non-fatal dose of aqueous and ethanolic extracts, both of which exert activity, were 0.5 g/kg and 5 g/kg. It seems that the anti-seizure profile might be related in part to the coumarin compounds isolated from C. sativum.

4.7. Caesalpinia bonducella (L.) Roxb.

The antiepileptic activity of C. bonducella was investigated using MES-, PTZ-, and picrotoxin-induced convulsion models. Petroleum ether extract was active in all tests, and at the dose of 600 mg/kg, it increased the threshold for convulsions and delayed the onset of tonic convulsions. It can be concluded that the extract showed its effectiveness through possibly blocking the chloride ion channel linked to GABA receptors.

4.8. Ferula gummosa Boiss.

The effects of the seed acetone extract of F. gummosa on epilepsy and sedation were evaluated. Test results revealed that F. gummosa protected mice against tonic convulsions induced by MES and PTZ. It produced a more potent protective effect against seizures induced by PTZ (ED50 = 55 mg/kg) than MES-induced seizures (ED50 = 198.3 mg/kg). Neurotoxicity (sedation and motor deficit) of the acetone extract assessed by the rotarod test were obtained dose-dependently with a TD50 value of 375.8 against MES- and PTZ-induced seizures.

In another study Sayyah et al. investigated the anticonvulsant effect of fruit essential oil of F. gummosa. The study revealed that the fruit essential oil of F. gummosa blocked PTZ-induced (though not MES-induced) seizures in mice. The LD50 (2.62 ml/kg) value of neurotoxicity, however, was too close to the anticonvulsant dose (2.5 ml/kg).

4.9. Cuscuta epithymum Murray

The anticonvulsant activity of hydro-alcoholic extract of C. epithymum was investigated using the PTZ test. Results showed that at a dose of 100 mg/kg, C. epithymum significantly increased seizure latency and percentage of survival, but no significant difference between convulsion duration with plant extract and the negative control was observed.

4.10. Cedrus deodara Loudon

Dhayabaran et al. investigated the alcoholic extract of heart wood of C. deodara (ALCD) for its anxiolytic effect in three experimental models, including elevated plus maze test, light dark model, and locomotor activity by actophotometer and anticonvulsant activity using PTZ- and MES-induced convulsions. The results showed that pretreatment with ALCD at doses of 100 and 200 mg/kg (po) significantly delayed the onset and duration of seizures induced by PTZ and MES and exhibited significant anxiolytic activity by modulating GABA levels in the brain in a dose-dependent manner.

4.11. Origanum majorana L.

Deshmane et al. investigated the antiepileptic and sedative properties of different extracts of aerial parts of O. majorana using PTZ and MES tests. All the extracts delayed the onset and reduced the duration of seizures in the PTZ test and decreased the duration of seizures in the MES test. Chloroform extract exhibited the maximum reduction in the seizure duration (48.5% inhibition at 250 mg/mL). Bioassay-guided fractionation led to the identification of triterpenoic acid fraction containing substantial amounts of ursolic acid as the active principle, which have been identified as a major compound responsible for plant activity (55.6% inhibition at 250 mg/mL). The test extracts also decreased latency and increased the duration of total sleeping time significantly.

By Shamim Sahranavard, Saeedeh Ghafari, Mahmoud Mosaddegh