Phototoxic effects of Hypericum extract in cultures of human keratinocytescompared with those of psoralen

Extracts of Hypericum perforatum (St, John"s wort) are used in the treatmen t of depression. They contain the plant pigment hypericin and hypericin der ivates, These compounds have light-dependent activities. In order to estima te the potential risk of phototoxic: skin damage during antidepressive ther apy, we Investigated the phototoxic activity of hypepicin extract using cul tures of human keratinocytes and compared it with the effect of the well-kn own phototoxic agent psoralen. The absorbance spectrum of our Hypericum ext ract revealed maxima in the whole UV range and in Darts of the visible rang e. We cultivated human keratinocytes in the presence of different Hypericum concentrations and irradiated the cells with 150 mJ/cm(2) UVB, 1 J/cm(2) U VA or 3 h with a white light of photon flux density 2.6; mu mol m(-2) s(-1) . The determination of the bromodeoxyuridine incorporation rate showed a co ncentration- and light-dependent decrease in DNA synthesis with high hyperi cin concentrations (greater than or equal to 50 mu g/mL) combined with UVA or visible light radiation. In the case of UVB irradiation a clear phototox ic cell reaction was not detected. We found phototoxic effects even with 10 ng/mL psoralen using UVA with the same study design as in the case of the Hypericum extract. These results confirm the phototoxic activity of Hyperic um extract on human keratinocytes, However, the blood levels that are to be expected during antidepressive therapy are presumably too low to induce ph ototoxic skin reactions.