Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes

Extracts of Hypericum perforatum, commonly known as St. John's wort, are frequently used in Germany and other European countries to treat mild to moderately severe depression, but the mechanism of antidepressant activity of Hypericum is not understood. Because known mechanisms of antidepressant activity include inhibition of serotonin and/or norepinephrine uptake, we investigated the effects of standardized extracts of Hypericum LI 160 on the transport of these monoamine neurotransmitters into astrocytes, cells which surround synaptic terminals and regulate neurotransmission by means of their uptake systems. We found that LI 160 inhibited both serotonin and norepinephrine uptake in a dose-dependent manner. The two monoamine transport systems were affected differently by LI 160: for serotonin, the main effect was a 50% decrease in the rate of maximal transport, whereas for norepinephrine, the main effect was a 4.5 fold reduction in the apparent affinity of norepinephrine for its uptake sites. Upon removal of LI 160, uptake was restored, thereby indicating that the inhibition was not due to a toxic effect of Hypericum on the cells. These findings suggest that the ability of LI 160 to inhibit serotonin and norepinephrine uptake may underlie the antidepressant activity of this Hypericum extract.