Molecular mechanisms underlying St. John's wort drug interactions.
The phytopharmaceutical agent St. John's wort (SJW) is currently under intense investigation. Studies of drug interactions resulting from concomitant use of SJW and conventional medication are of fundamental importance, since the use of SJW as a complementary and alternative medicine is highly popular. Intake of SJW often remains unrecognized by physicians resulting in clinical relevant alterations of treatment, as this phytopharmaceutical agent is available without prescription. This review elicits molecular explanations for clinical observations in terms of concomitant use of SJW and conventional drugs. Since patients suffering from severe diseases such as cancer are especially at risk, we focus on chemotherapeutic agents. There is strong evidence that SJW extract lowers drug plasma levels of various anti-cancer agents by pregnane X receptor activation resulting in induction of cytochrome P450 isotype 3A4, P glycoprotein and several other enzymes. New methods such as photophysical diagnosis (PPD) and photodynamic therapy (PDT) seem to be highly promising with respect to their clinical application. Due to its fluorescent activity and an intense accumulation in cancer cells, hypericin could be applied to locate tumorous tissues. Upon excitation by light, hypericin generates cytotoxic products rendering its use attractive as photosensitizing agent. In this review both PPD and PDT are explained in detail, with a particular focus on molecular mechanisms.
Kober
Maike
M
Institute of Pharmacy and Molecular Biotechnology, Ruprecht Karls University, Heidelberg, Germany.
Pohl
Kerstin
K
Efferth
Thomas
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000818:Animals; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000502:physiology; D004790:Enzyme Induction; D041743:Herb-Drug Interactions; D006801:Humans; D020902:Hypericum; D010569:Perylene / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D010778:Photochemotherapy
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000873:Anthracenes; D000970:Antineoplastic Agents; D010569:Perylene; C004965:hypericin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human