Apigenin, a Component ofMatricaria recutitaFlowers, is a Central Benzodiazepine Receptors-Ligand with Anxiolytic Effects

Abstract

The dried flower heads of Matricaria recutita L. (Asteraceae) are used in folk medicine to prepare a spasmolytic and sedative tea. Our fractionation of the aqueous extract of this plant led to the detection of several fractions with significant affinity for the central benzodiazepine receptor and to the isolation and identification of 5,7,4'-trihydroxyflavone (apigenin) in one of them. Apigenin competitively inhibited the binding of flunitrazepam with a Ki of 4 microM and had no effect on muscarinic receptors, alpha 1-adrenoceptors, and on the binding of muscimol to GABAA receptors. Apigenin had a clear anxiolytic activity in mice in the elevated plusmaze without evidencing sedation or muscle relaxant effects at doses similar to those used for classical benzodiazepines and no anticonvulsant action was detected. However, a 10-fold increase in dosage produced a mild sedative effect since a 26% reduction in ambulatory locomotor activity and a 35% decrement in hole-board parameters were evident. The results reported in this paper demonstrate that apigenin is a ligand for the central benzodiazepine receptors exerting anxiolytic and slight sedative effects but not being anticonvulsant or myorelaxant.

Antidepressant-Like Effects of Apigenin and 2,4,5-Trimethoxycinnamic Acid from Perilla frutescens in the Forced Swimming Test.

“…However, it is also possible that the ability of apigenin to decrease the immobility in the forced swimming test may be simply due to the increased spontaneous motor activity such as psychostimulants, but Viola et al and Zanoli et al reported that at least apigenin doses up to 100 mg/kg did not increase the spontaneous motor activity. 13,15) Thus, the apigenin induced decrease in the immobility seems not to be mediated by stimulation of the overall motor activity of the animals. On the 478 Vol.…”

“…However, if apigenin decreased the GABA-activated Cl Ϫ currents, apigenin should exhibit an anxiogenic effect, but Viola et al and Salgueiro et al reported that apigenin exhibits anxiolytic activity in mice without any sedative or myorelaxant effects. 13,33) Thus, there are discrepancies in reporting the ability of apigenin to GABA activity.…”

“…1) were detected in the plasma and urine when an aqueous extract of P. frutescens was administered to humans. 12) Moreover, it has been reported that apigenin possesses a variety of pharmacological actions on the central nervous system, such as anxiolytic and sedative properties, [13][14][15] while to our knowledge, the effect of TMCA is not well characterized.The purpose of the present study was to examine the effect of treatment with apigenin and TMCA on immobility in the forced swimming test, which has been a useful experimental method for screening antidepressant activity, as a wide range of antidepressants, including tricyclics, monoamine oxidase inhibitors, atypicals, by reducing the duration of immobility. 16,17) Moreover, in addition to the behavioral change in the forced swimming test, the levels of norepinephrine (NE), dopamine (DA), 5-hydroxytriptamine (5-HT), and their metabolites in the striatum, hippocampus, amygdala, frontal cortex, thalamus, hypothalamus, and midbrain were used as parameters for evaluating antidepressant activity of apigenin and TMCA, and the effect of dopaminergic blockade on the anti-immobility action of apigenin in the forced swimming test was also investigated.…”

“…1) were detected in the plasma and urine when an aqueous extract of P. frutescens was administered to humans. 12) Moreover, it has been reported that apigenin possesses a variety of pharmacological actions on the central nervous system, such as anxiolytic and sedative properties, [13][14][15] while to our knowledge, the effect of TMCA is not well characterized.…”

“…18,19) The dose of apigenin was chosen without affecting the general motor activity that would allow us to evaluate whether the drug treatment increased or decreased the behavior. [13][14][15] Forced Swimming Test The procedure was a modification of the method described by Porsolt et al 16,17) Mice were placed in a glass aquarium (15 cmϫ12 cm diameter) containing 9 cm deep cold water (23Ϯ1°C) for 15 min followed by a 5-min retest (test session) 24 h later. Immobility time was recorded during the test session: the mouse was considered immobile whenever it stopped swimming and remained floating in the water, with its head just above water level.…”