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Source Review: Yoshino, K., Higashi, N., & Koga, K. (2006). Antioxidant and antiinflammatory activities of oregano extract. Journal of health science, 52(2), 169-173.
Inflammatory diseases due to lifestyle changes like dietary habits can cause serious health issues like digestive ulcers, chronic gastritis, and gastric cancer.
Hydrochloric acid, digestive enzymes, and bacteria in the digestive system can cause damage to mucous membranes which can cause the production of active oxygen species like nitrogen monoxide and anion radicals.
These active oxygen species can directly injure surrounding cells and produce peroxides and other metabolites of acids that can continue to cause more damage which overall promotes inflammation.
Antioxidants are known to suppress inflammation in rat arthritis models.
They can directly scavenge for radicals and act as electron donors for peroxidases (PODs) which helps decompose hydrogen peroxide through a catalytic reaction.
Many herbs include some antioxidant components, and oregano is one such herb.
Some active components in Oregano include rosmarinic acid, caffeic acid, and various flavinoids.
All of these components can also act as substrates in the catalytic reaction for PODs.
To obtain these active components from the plant, commercial oregano leaves were ground up in a mill, added in a ethanol, and shaken at 122 degrees Fahrenheit for an hour. The mixture was then centrifuged at 5000 rpm for 10 minutes. The supernatant was separated, evaporated in vacuum, and then lyophilized (frozen). The oregano extract remains.
To measure the activity of the oregano extract active components as a POD substrate, horseradish POD was added in with oregano extract and hydrogen peroxide and the decomposition was compared to a control and a positive control (phenol, which has a known strong catalytic response).
To measure antioxidant activity, the oregano extract was added in with ferric chloride and the iron-reducing activity was tracked and compared to a standard.
To test reduction of gastric inflammation, mice were give the oregano extract and stressed. After 24 hours of starvation in cold they were killed and their stomachs were examined. The amount of bleeding points were compared to a control and hydrocortisone (a known anti inflammatory agent).
Finally contact hypersensitivity was tested with and without the oregano extract to see if the extract reduced skin swelling (a form of inflammation).
This was tested through applying a compound to make an area of the mouse sensitive, then applying a compound which actively causes swelling. The extract, hydrocortisone, and a control were then added to see which helps reduced swelling.
Oregano extract performed at 60.6 percentage of the phenol as a POD substrate, suggesting it is a good electron donor for POD. This is compared to two other herb extracts, laurel and marjoram, which are known antioxidants, which performed at 28.1 and 25.8 percentage.
It performed as an antioxidant by reducing the iron compound, but not as well as ascorbic acid (Vitamin C). Its iron-reducing ability was roughly half of ascorbic acid.
In the mice studies, oregano extract performed similarly to the hydrocortisone at lower doses where it reduced bleeding points by 30.5 to 34.0 percentage compared to hydrocortisone’s reduction of 47.5 to 49.5 percentage. However at higher doses, hydrocortisone performed much better than oregano extract (80.0 compared to 35.0 percentage).
In the testing of the inhibition of contact hypersensitivity, the oregano extract reduced swelling by up to 47.4 percentage. The hydrocortisone reduced swelling by up to 74.7 percentage.
Mouse contact hypersensitivity is known to be suppressed by antioxidants and thus the antioxidant activity of oregano extract is suggested to be what helped with the reduction in swelling.
Peroxide levels are also known to raise in mice subjected to cold and starvation, implying that the reduction in bleeding points could be from the use of the oregano extract’s active components as a substrate for POD.
While this study implies general oregano extract can reduce gastric inflammation and act as an antioxidant, it doesn’t specify which active component of the extract is promoting these activities and more studies would need to be done to confirm which are actually active.
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.