St John's Wort Research - Depression, Anxiety, Side-effects, Dosage, Benefits

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Usefulness of studies on the molecular mechanism of action of herbals/botanicals: The case of St. John's wort.

Choudhuri S, Valerio LG

Division of Biotechnology and GRAS Notice Review, Office of Food Additive Safety, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD 20740, USA. Supratim.Choudhuri@cfsan.fda.gov

The use of herbals/botanicals has been gaining wide popularity in recent years in the United States as well as in other parts of the world. The mechanism of action of most of these herbals/botanicals has not been subjected to thorough scientific investigations. St. John's wort (Hypericum perforatum) represents a useful case study in this sense. Traditionally, it is used as a natural treatment for depression; however, in recent years its molecular mechanism of action has been elucidated by a number of laboratories across the world. Such studies have helped understand potential interactions of St. John's wort with drugs and other xenobiotics. St. John's wort activates a nuclear receptor called pregnane X receptor (PXR). PXR is a ligand-activated transcription factor that induces a number of xenobiotic-metabolizing enzymes and transporters including cytochrome P4503A4 (CYP3A4) in humans. Because CYP3A4 alone metabolizes about 60% of all clinically relevant drugs, induction of CYP3A4 may result in the rapid elimination of these drugs and a consequent reduction in drug efficacy. Ironically, such enzyme-inducing effects may not produce any immediate adverse symptomatology in the person taking St. John's wort. Therefore, the case of St. John's wort should serve as a good example of the usefulness and importance of studies on the mechanism of action of the herbals/botanicals, particularly those with widespread use. Scientists, physicians, and other health professionals can make use of the knowledge from such studies as an additional risk management tool.

Published 7 March 2005 in J Biochem Mol Toxicol, 19(1): 1-11.
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St John's Wort Books

St. John's Wort and its Active Principles in Depression and Anxiety (Milestones in Drug Therapy)

St. John's Wort and its Active Principles in Depression and Anxiety (Milestones in Drug Therapy)