The plant Hypericum perforatum is used in folk medicine to treat several diseases and research attention has been recently focused on its antidepressant action. Hypericin and flavonoids are the most important constituents of the plant, but the exact role of these compounds in the effects of hypericum on mood disorders is not well known. We have investigated the contribution of these compounds to the antidepressant effects of hypericum. The effects of acute administration of hypericum extracts on levels of 5-hydroxytryptamine (5-HT), tryptophan, 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline and dopamine in the cortex, diencephalon and brainstem was evaluated. The levels of these neurotransmitters were measured 1 h and 24 h after administration of two different extracts, one containing 0.3% hypericin and 6% flavonoids (Li 160; 25-500 mgkg(-1)), the other containing 0.3% hypericin and 50% flavonoids (Ph-50; 25-500 mgkg(-1)). Results from experiments performed on 5-HT turnover were compared with the effects of fluoxetine (10-80 mgkg(-1)). Li 160, Ph-50 and fluoxetine induced a significant increase in the 5-HT content of the cortex. In the diencephalon Ph-50, but not Li 160 or fluoxetine, elicited an increase in 5-HT and 5-HIAA levels. In the brainstem Ph-50 and fluoxetine caused an increase in 5-HT content; Li 160 did not change neurotransmitter content. Both Li 160 and Ph-50 caused increases of noradrenaline and dopamine in the diencephalon. In the brainstem only Ph-50 induced an increase in noradrenaline content. Our data confirm that acute administration of hypericum extracts modifies the levels of neurotransmitters involved in the pathophysiology of mood disorders. When the extracts contain a higher concentration of flavonoids the effects are more widespread and involve brain regions such as diencephalon and brainstem that are implicated in depression.
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