Interleukin-6 Involvement in Antidepressant Action of Hypericum Perforatum

Abstract

Hypericum, a plant widely used as antidepressant has been shown to interact with the immune system. We studied the effects of the administration of the 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-hydroxyindoleacetic acid (5-HIAA) diencephalic content using a high performance liquid chromatography method in male interleukin-6 (IL-6) knock-out (IL-6(-/-)) and wild type (IL-6(+/+)) mice. Hypericum extract (Ph-50; 500 mg/kg) oral acute administration reduced the immobility time of wild type, but not of knockout mice. Tryptophan content was not modified by Hypericum in all the animal groups. Serotonin and 5-HIAA diencephalic content was increased by Hypericum 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 activation of the serotonin system.

Beneficial Effect of Chronic Treatment with Extracts from Rhodiola Rosea L. and Curcuma Longa L. on the Immunoreactivity of Animals Subjected to a Chronic Mild Stress Model

“…34 Calapai et al showed that IL-6 was necessary for the antidepressant action of Hypericum perforatum and that the activation of the central serotonergic metabolism following Hypericum perforatum may be attributed to increased IL-6. 35 Our data about the increased IL-6 level in all experimental groups treated with both extracts suggest similar mechanisms involved and could be interpreted as a manifestation of anti-depressant action. This idea is also supported when the results from the behavioral test and the cytokines evaluation are taken together.…”

Stimulatory effect of antidepressants on the production of IL-6

“…The extract of H. perforatum reduced immobility in a forced swimming test in wild-type mice, but not in IL-6 knock-out animals. Moreover, H. perforatum induced significantly higher increases in diencephalon 5-HT and 5-HIAA levels in wild mice than in IL-6 knockout animals [32]. In our earlier study, we observed a stimulatory effect of 5-week daily administration of imipramine to rats subjected to a chronic mild stress model of depression on IL-6 production [6].…”

“…It may thus be speculated that the therapeutic activity of these drugs is at least partly connected with their effect on IL-6 production. Calapai et al [32] showed that IL-6 was necessary for the antidepressant action of Hypericum perforatum and that the activation of the central serotonergic metabolism following Hypericum perforatum may be attributed to increased IL-6. H. perforatum (St. John's wort) has been used medicinally for thousands of years and has recently been employed in the treatment of mild-to-moderate depression, although its effectiveness is still a matter of controversy.…”

Anti-Inflammatory Actions of St. John's Wort: Inhibition of Human Inducible Nitric-Oxide Synthase Expression by Down-Regulating Signal Transducer and Activator of Transcription-1α (STAT-1α) Activation

“…There are some reports attributing the anti-inflammatory effects of SJW or its ingredient quercetin to inhibition of nuclear factor-B (NF-B) activation (Bork et al, 1999), inhibition of protein kinase C (Agostinis et al, 1996), and reduction of the lipopolysaccharide-, cytokine-, or substance P-induced expression of cyclooxygenase-2 (Raso et al, 2001(Raso et al, , 2002; inducible nitric-oxide synthase (iNOS) (Raso et al, 2001(Raso et al, , 2002Wang and Mazza, 2002) or interleukin-6 (Fiebich et al, 2001). Also its antidepressive effect has been attributed to the inhibition of interleukin-6 synthesis (Calapai et al, 2001).…”