Abstract

Despite being traditionally used herbals to treat mild anxiety and sleep disorders, Valeriana officinalis and Melissa officinalis mechanism of action is not fully understood. While the pattern of mood modulation of both herbals suggests the involvement of the Gamma-Aminobutyric Acid (GABA) ergic system, other changes in the neurotransmitters pathways can provide an explanation for the clinical effects. The aim of this study was to examine the combined mechanism of action of the two extracts in order to explain the anxiolytic and calming effects that may facilitate sleep induction and improve sleep quality in patients with mild to moderate sleep disturbances. These effects have been previously reported in the literature for a botanical product combining 120 mg Valeriana officinalis and 80 mg of Melissa officinalis standardized extracts (Songha® Night). To assess mechanism of action we employed the Unpredictable Chronic Mild Stress (UCMS) animal model, as it has strong predictive validity. Brain GABA and glutamate levels were sampled using a microdialysis technique and measured by HPLC. Additional in vitro experiments investigated the effects of the extracts on Group II Metabotropic Glutamate Receptors (mGlu2) binding and GABA Transaminase (GABA-T) activity. Results indicate that the two extracts together exert a functional synergism leading to normalization of brain levels of GABA and glutamate altered by stress. In vitro experiments reveal that the combination of both extracts could inhibit GABA-T activity more effectively than the single extracts and that Valeriana officinalis binds mGlu2 receptors. Altogether these results demonstrate a synergistic effect of Valeriana officinalis and Melissa officinalis standardized extracts on counteracting the alterations in neurotransmitter levels caused by chronic stress and support the tranquilizing and sleep inducing activity of Songha® Night observed in clinical trials.

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