Pharmacological profile of an essential oil derived from Melissa officinalis with anti-agitation properties: focus on ligand-gated channels

Abstract

A dual radioligand binding and electrophysiological study, focusing on a range of ligand-gated ion channels, was performed with a chemically-validated essential oil derived from Melissa officinalis (MO), which has shown clinical benefit in treating agitation. MO inhibited binding of [35S] t-butylbicyclophosphorothionate (TBPS) to the rat forebrain gamma-aminobutyric acid (GABA)(A) receptor channel (apparent IC50 0.040+/-0.001 mg mL(-1)), but had no effect on N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropianate (AMPA) or nicotinic acetylcholine receptors. Electrophysiological analyses with primary cultures of rat cortical neurons demonstrated that MO reversibly inhibited GABA-induced currents in a concentration-dependent manner (0.01-1 mg mL(-1)), whereas no inhibition of NMDA- or AMPA-induced currents was noted. Interestingly, MO elicited a significant dose-dependent reduction in both inhibitory and excitatory transmission, with a net depressant effect on neurotransmission (in contrast to the classical GABA(A) antagonist picrotoxinin which evoked profound epileptiform burst firing in these cells). The anti-agitation effects in patients and the depressant effects of MO in in-vitro we report in neural membranes are unlikely to reflect a sedative interaction with any of the ionotropic receptors examined here.

Identification of a Novel GABAA Receptor Channel Ligand Derived from Melissa officinalis and Lavandula angustifolia Essential Oils

“…This batch of (Mo) was selected and validated based on previous pharmacological and chemical studies using batches from four common suppliers (Baldwins (London, UK), Pranarom (Lille, France), Quinessence (Coalville, UK), Fytosan (Die, France); the composition correlates with the natural products Herbal Pharmacopoeia standards and was confirmed to be stable throughout the research programme (Dr Melanie-Jayne Howes, Jodrell Laboratory, Kew Gardens). Furthermore, a batch was selected and used in a parallel clinical trial in late-stage of Alzheimer's disease patients [18,19]. The GC-MS profile carried out at the Royal Botanic Garden at Kew (London), displayed no major changes in (Mo) composition following long-term storage (18 months) at 4°C in the dark (composition reported previously in [18,19]).…”

“…Furthermore, a batch was selected and used in a parallel clinical trial in late-stage of Alzheimer's disease patients [18,19]. The GC-MS profile carried out at the Royal Botanic Garden at Kew (London), displayed no major changes in (Mo) composition following long-term storage (18 months) at 4°C in the dark (composition reported previously in [18,19]). Dilutions of essential oil stocks or components were performed fresh on the day of assay.…”

“…Previous studies [18,19] suggest that (Mo) may display neuro protective properties, via a sodium channel blockade mechanism. This potential was investigated using a primary neuronal culture system as described in [16].…”

“…The great molecular diversity of the multi-subunit hetero-oligomeric GABA A receptor provides opportunities to develop novel drugs, for example for anxiety, sleep disorders, alcoholism and epilepsy by establishing the relevant molecular targets for receptor subtype specific action [15][16][17]. In this present report, we attempted to identify the component that probably accounts for GABA A receptor binding properties of the Melissa and Lavender essential oils [18,19].…”

Use of medicinal herbs by patients with severe asthma managed at a Referral Center

“…Examining the supposed pharmacological properties of the plants most cited by the patients, reveals that the majority are used as antispasmodics, tranquilizers or antiinflammatory drugs (Abuhamdah et al 2008;Tirapelli et al, 2007;McKay, Blumberg, 2006). These properties could contribute to the control of asthma symptoms, but should not be indicated for treatment of this disease due lack of evidence of their efficacy and safety.…”