Interleukin-6 involvement in antidepressant action of Hypericum perforatum

Hypericum, a plant widely used as antidepressant has been shown to interact with the immune system. We studied the effects of the administration of th e Hypericum perforatum extract Ph-50, a Hypericum extract, standardized to flavonoids (50%) and containing 0.3% of hypericin and 4.5% of hyperforin in a forced swimming test and tryptophan, serotonin (5-HT) and 5-hydroxyindol eacetic acid (5-HIAA) diencephalic content using a high performance liquid chromatography method in male interleukin-6 (IL-6) knock-out (IL-6(-/-)) an d wild type (IL-6(+/+)) mice. Hypericum extract (Ph-50; 500 mg/kg) oral acu te administration reduced the immobility time of wild type, but not of knoc kout mice. Tryptophan content was not modified by Hypericum in all the anim al groups. Serotonin and 5-HIAA diencephalic content was increased by Hyper icum in both wild type and knockout mice. However, the increase observed in the wild type was greater than in knockout mice. These data indicate that IL-6 could be necessary to the antidepressant action of Hypericum, and that this cytokine (probably) mediates the effects of Hypericum through activat ion of the serotonin system.