Mechan, A. O., Fowler, A., Seifert, N., Rieger, H., Wöhrle, T., Etheve, S., … & Aston, J. (2011). Monoamine reuptake inhibition and mood-enhancing potential of a specified oregano extract. British journal of nutrition, 105(8), 1150-1163.
Serotonin, dopamine, and noradrenaline (NA) are all considered monoamine neurotransmitters and play an important role in brain development and function.
To synthesize these neurotransmitters, serotonin requires the essential amino acid tryptophan, while dopamine and NA require tyrosine. The rate of synthesis is sensitive to the supply of these respective amino acids.
Neurotransmitters work through being released into the synaptic cleft following their synthesis. They then interact with post-synaptic receptor sites.
To stop their interaction with these sites, the neurotransmitters can be taken back into the pre- synaptic neuron through reuptake transporters or through enzymatic degradation with monoamine oxidase (MAO).
Thus these neurotransmitter’s activity can be increased through inhibition of MAO, or through inhibition of the reuptake transporters.
Each neurotransmitter has specific impacts on brain and behavioral functions, to start serotonin “is implicated in cardiovascular regulation, respiration and thermoregulation, as well as in circadian rhythm entrainment, the sleep–wake cycle, appetite, mood, aggression, sexual behaviour, sensorimotor reactivity, pain sensitivity and learning”.
Dopamine “is involved in locomotor activity, cognition, emotion, positive reinforcement, food intake and endocrine regulation”.
Noradrenaline “is involved in mediating attention, anxiety, arousal, food intake and learning and memory”.
With this taken in consideration, nutritional components and supplements have been shown to impact these categories in multi- faceted ways, alluding to their impact on many different types of brain function, through various neurotransmitters. Many of these nutritional components include essential oils or extracts from various plants.
One of these plants, oregano, has shown particular promise. When using a two-step supercritical fluid CO2 extraction to receive a specified range of active constituents, it was shown to have strong inhibitory activity. It was shown to inhibit reuptake of serotonin, NA, and dopamine, as well as inhibiting MAO-A enzymatic activity. This was further confirmed by showing carvacrol (CAR), the main constituent in oregano extract, to be in dose- dependent levels in mice tissue following a dosing schedule implying it’s reach into the brain.
This effect was corresponded with antidepressant-like and anxiolytic-like impacts in mice.
To prepare this extract, dried oregano leaves were mechanically milled and extracted with CO2 at 1450 psi and 113 degrees Fahrenheit. The overall flow was 1 pound of CO2 per pound of plant material. The solvent was removed in a secondary step at 870 psi and 86 degrees Fahrenheit.
This produced an extract with a total essential oil content of 89 percentage. The components of this extract included “terpinene (0 to 2 percentage), thymol (0.2 to 0.4 percentage), 4-terpineol (0.3 to 1.5 percentage), caryophyllene (1.5 to 1.9 percentage), p-cymene (2.4 to 7.8 percentage), thymoquinone (4 to 23.2 percentage) and CAR (50 to 79.9 percentage)”.
The in-vitro (meaning “done in a petri dish”) procedures are quite long and complex, but can be summarized by using fetal calf serum cells with reagents, radioactivity, fluorescent compounds, and varying conditions to track the concentrations of neurotransmitters in the presence of the oregano extract, reuptake transporters, and MAO-A (tracked through GC/MS).
The in-vivo determinations are a little more understandable. Mice were given the oregano extract in doses and sent through various behavioral tests to track the activity of the extract. To track anti-depression activity, the mice were put into tubes filled with water that they could not escape and their behaviors were analyzed as time continued. To test anxioltic activity, or obsessive-compulsive behavior, mice in a cage were given marbles, and the total amount of marbles covered in saw dust at the end of a 15 minute interval was recorded. Also to test the anxiolytic activity, the mice were placed in a separated box with a lit and dark area and the time spent in the lit compartment was recorded.
These tests have specific behaviors to look for and standard results with certain mouse breeds to compare with the results received in the study. The study also included control groups.
To track the concentration of serotonin levels, a probe was added into a living mouse brain under anesthetic. This probe saturates with certain compounds, which is then analyzed with HPLC afterwards.
To track CAR levels, after dosing, the mice were killed while simultaneously pulling out blood and brain tissue. These samples were then tested for CAR levels.
As thymoquinone and/or CAR were increased in concentration, the levels of serotonin reuptake inhibition increased, pointing to the importance of these two compounds in serotonin activity.
In the forced swim test, there was a significant reduction in immobility in the groups given the oregano extract. Acute dosing reduced immobility by up to 24 percentage and chronic dosing reduced immobility by up to 41 percentage compared to control groups. This was close to the reference compounds 51 to 70 percentage (reference compounds include ones known to induce the sought after behavior, like antidepressants or anti-anxiety medication). In the marble burying test, there was a reduction of up to 73 percentage less marbles buried with the oregano extract compared to the control groups, compared to the reference compounds reduction of 93 to 98 percentage.
In the light/dark box, oregano extract increased time spent in the light portion by up
to 35 percentage compared to control groups and up to 114 percentage with the reference compounds.
All of these behavioral tests were far past significant compared to the control groups.
When looking at the levels of serotonin, there was a marked increase in brain extra cellular serotonin levels in rats given the oregano extract. This impact stops shortly after stopping the doses of oregano extract (around a day). However, when comparing to the clinical antidepressants, the influence was up to 1000-fold lower. While this isn’t extremely promising, in conjunction with the behavioral impacts, it implies that oregano extract could be used as a mood-enhancing supplement that does not display the side- effects seen with antidepressants. It also does not have a lasting impact on brain chemistry even with chronic dosing.