St John's Wort (SJW) extracts are herbal products which are available without prescription in most countries and widely used in the treatment of mild to moderate depression. Since it is a herbal product and available without prescription, use of SJW is common among pregnant and/or lactating woman. The principal of the study was to clarify the effects of hypericin, one of the components of SJW, on glutathione S-transferase-pi (GST-pi) purified from human placenta. The K (m) values of GST-pi were 0.21 +/- A 0.03 mM for glutathione (GSH) and 2.29 +/- A 0.54 mM for 1-chloro-2,4-dinitrobenzene (CDNB). At fixed [GSH], the V (m) value calculated was about 3 times higher than the conditions in which [CDNB] was fixed; 201 +/- A 30 U/mg protein versus 74 +/- A 3 U/mg protein. At constant substrate concentrations (1 mM), an average IC (50) value of 0.70 +/- A 0.02 mu M was obtained. Hypericin inhibited GST-pi competitively with respect to both substrates. When GSH was the varied substrate a K (i) value of 0.31 +/- A 0.05 mu M was found; when CDNB was the varied substrate, a K (i) value of 0.85 +/- A 0.02 mu M was obtained. On the basis of these data considering transplacental transfer of hypericin and immature hepatic clearance of the baby, using this herbal product may cause abnormalites due to the inhibition of one of the most important placental detoxification enzymes, GST-pi.