Phototoxic Effects of Hypericum Extract in Cultures of Human Keratinocytes Compared with Those of Psoralen

Abstract

Extracts of Hypericum perforatum (St. John's wort) are used in the treatment of depression. They contain the plant pigment hypericin and hypericin derivates. These compounds have light-dependent activities. In order to estimate the potential risk of phototoxic skin damage during antidepressive therapy, we investigated the phototoxic activity of hypericin extract using cultures of human keratinocytes and compared it with the effect of the well-known phototoxic agent psoralen. The absorbance spectrum of our Hypericum extract revealed maxima in the whole UV range and in parts of the visible range. We cultivated human keratinocytes in the presence of different Hypericum concentrations and irradiated the cells with 150 mJ/cm2 UVB, 1 J/cm2 UVA or 3 h with a white light of photon flux density 2.6 mumol m-2 s-1. The determination of the bromodeoxyuridine incorporation rate showed a concentration- and light-dependent decrease in DNA synthesis with high hypericin concentrations (> or = 50 micrograms/mL) combined with UVA or visible light radiation. In the case of UVB irradiation a clear phototoxic 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 Hypericum extract on human keratinocytes. However, the blood levels that are to be expected during antidepressive therapy are presumably too low to induce phototoxic skin reactions.

Differential susceptibility of primary cultured human skin cells to hypericin PDT in an in vitro model

“…This cell line was however an immortalised line [31]. This initial study was followed by Bernd et al who reported on the cytotoxic effect of a hypericum extract on cultures of human keratinocytes [32]. Similarly, this group used an immortal keratinocyte cell line (HaCaT).…”

Influence of GSTT1 and GSTM1 Genotypes on Sunburn Sensitivity

“…[13] Its most specific ingredients, naphthodianthrones hypericin and pseudohypericin, have both been shown to produce singlet oxygen by photooxidative reaction in cell cultures. [14][15][16][17][18] Singlet oxygen is the most likely cause of the observed phototoxicity in animals. [19] Glutathione S-transferases (GSTs) contribute to the cellular defense system against oxidative stress by their peroxidase activity, and by detoxifying xenobiotics, which serve as cofactors in radical formation.…”

Use of Complementary Medicines by Cardiac Surgery Patients; Undisclosed and Undetected

“…For example, St Johns wort is an effective and well tolerated treatment for mild to moderate depression and is generally safe as stand-alone treatment, however, it can induce adverse outcomes when used together with medications such as digoxin, warfarin or midazolam due to pharmacokinetic interactions [22]. It can also induce phototoxic skin reactions when used in high doses due to the presence of a naturally occurring pigment, hypericin [23].…”