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DOI: 10.1055/s-2008-1047812
Electropharmacogram from quercetin is similar to that of moclobemide and other antidepressant drugs
Background
Neurotransmitter action in the brain is always accompanied by changes in electrical activity. These are reflected in the electropharmacograms based on quantitative field potential recording in the presence of drugs. Recording from four brain areas and dividing the spectral frequency data into six ranges provides 24 variables for construction of the electropharmacogram (pattern of electrical pre-post changes of drug action).
Method
Adult rats (>5 month old) were instrumented by four bipolar concentric electrodes connected by a small base plate which was positioned stereotactically for insertion of the electrodes into the frontal cortex, hippocampus, striatum and reticular formation. The plate carried a small plug for receiving a telemetric device during the experimental session. Changes of field potentials were recorded during a pre-drug reference period of 45min followed by oral administration of the plant derived ingredients and 5h recording thereafter. Data were transmitted wirelessly to the computer for frequency analysis and partition into six frequency ranges (delta, theta, alpha1, alpha2, beta1 and beta2). Changes of power density were calculated continuously and averaged to give hourly values. Data from six animals treated within a crossover design were averaged and mean values analysed using multivariate statistics. Experiments were performed in concordance with German law on the use of animals in research.
Results
Following the administration of quercetin a dose dependent pattern of changes was observed. Decreases of spectral power (after 10, 20 or 40mg/kg) were observed mainly in the alpha2 and beta1 range, but also in the delta, theta and alpha1 range, predominantly in the hippocampus. Effects became stronger with time. Highest efficacy was at the 5th hour. The overall pattern of changes resembled that obtained after i.p. administration of the reference drugs moclobemide (a monoaminoxidase [MAO] A inhibitor), selegiline (a MAO B inhibitor) and other anti-depressant drugs like paroxetine or imipramine.
Conclusion
Since MAO inhibition has been reported in the literature also for quercetin (IC50 value: 2,8 microM for MAO A [1]; IC50 value: 7,95 microM for MAO B [2]), this mechanism of action could be common to all of these drugs and explain the similarity of the electropharmacograms. It could be of interest in this respect that MAO inhibition also has been reported for paroxetine and imipramine. Thus, quercetin, a major ingredient of St. John's Wort, could be responsible for its clinically proven antidepressant effects by inhibiting MAO.
[1] Han XH, Hong SS, et al.: Arch Pharm Res 2007; 30: 13–17.
[2] Lee MH, Lin RD, et al.: J Agric Food Chem 2001; 49: 5551–5.