Abstract
Melissa officinalis L. is used in traditional European and Iranian folk medicines to treat a plethora of neurological diseases including epilepsy. We utilized the in vitro and in vivo models of epilepsy to probe the anticonvulsant potentials of essential oil from M. officinalis (MO) to gain insight into the scientific basis for its applications in traditional medicine for the management of convulsive disorders. MO was evaluated for effects on maximal electroshock (MES) and pentylenetetrazole (PTZ) -induced seizures in mice, on 4–aminopyridine (4-AP)-brain slice model of epilepsy and sustained repetitive firing of current clamped neurons; and its ameliorative effects were examined on seizure severity, anxiety, depression, cognitive dysfunction, oxidative stress and neuronal cell loss in PTZ-kindled rats. MO reversibly blocked spontaneous ictal-like discharges in the 4-AP-brain slice model of epilepsy and secondary spikes from sustained repetitive firing, suggesting anticonvulsant effects and voltage-gated sodium channel blockade. MO protected mice from PTZ– and MES–induced seizures and mortality, and ameliorated seizure severity, fear-avoidance, depressive-like behavior, cognitive deficits, oxidative stress and neuronal cell loss in PTZ–kindled rats. The findings warrant further study for the potential use of MO and/or its constituent(s) as adjunctive therapy for epileptic patients.
Highlights
Epilepsy is a progressive and chronic neurological disorder characterized by unprovoked spontaneous recurrent seizures (SRS), ictal and inter-ictal events or generally asymptomatic bouts of population level activities that are measured between seizures
The principal constituents detected in the essential oil from M. officinalis by GC–MS were monoterpenes and sesquiterpenes (Table 1; Gas Chromatography-Mass Spectrometry (GC-MS) total ion chromatogram is shown in the Supplementary Figure S1), with composition data consistent with that previously reported for M. officinalis oil (Elliott et al, 2007), and with the citral chemotype reported for this species (Kittler et al, 2018a; 2018b)
Acute Seizure Studies In acute in vivo model, Melissa officinalis (MO) at doses between 10 and 100 mg/kg did not protect the mice from PTZ (85 mg/kg)-induced tonic hind limb extension
Summary
Epilepsy is a progressive and chronic neurological disorder characterized by unprovoked spontaneous recurrent seizures (SRS), ictal and inter-ictal events or generally asymptomatic bouts of population level activities that are measured between seizures. It is associated with profound physical, social and psychological consequences, and without age, racial, social, sexual or geographical boundaries (Gidal et al, 2002). In many patients with unexplained epilepsy, the generally accepted theory is that epilepsy is the result of an imbalance of certain neurotransmitters and/or ion channels that regulate membrane excitability. Neurotransmitters such as acetylcholine, aspartate, corticotrophin-releasing factor, cytokines, glutamate, histamine, noradrenaline, peptides, purines and steroid hormones enhance excitability and propagation of neuronal activity, whereas dopamine and γ-aminobutyric acid (GABA) inhibit neuronal activity and propagation (Rogers and Cavazos, 2008)
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