Potential Interactions of Herbal Extracts of St. John´s Wort with Metabolites of Diazepam in an Organotypical Sandwich Culture of Primary Porcine Hepatocytes.
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Date
2014-08
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Abstract
Extracts of St. John’s Wort (Hypericum perforatum) are known to cause interactions with
certain conventional drugs. Herein, we focus on two clinically relevant concepts. First, St.
John´s Wort has been used by people of all ages as an herbal treatment for depression
without medical prescription. Second, diazepam-like substances called endogenous
benzodiazepines are found in cases of acute liver failure without previous exposure to
diazepam. Currently diazepam has over 500 brands name and well marketed throughout
the world and became one most frequently prescribed medication in different form (oral,
injectable, inhalation and rectal forms) for four decades. Based on this concept, we
investigated diazepam biotransformation by incubation of a widely accepted in vitro
organotypical culture model with Hypericum methanolic extract, powdered drug, infusion,
oil, and with the pure Hypericum compounds hyperforin and hypericin. The amounts of the
preparations and compounds were chosen according to the recommended daily
medication doses. We measured the activities of ethoxyresorufin-O-deethylase (EROD),
ethoxy coumarin O-deethylase (ECOD) and the potential induction of diazepam metabolites (desmethyldiazepam, temazepam and oxazepam) during biotransformation.
None of the preparations or substances induced EROD or ECOD. However, different
preparations did induce the formation of desmethyldiazepam and temazepam. The
strongest activity was caused by the extract, followed by the powdered drug and
hyperforin. All preparations and compounds increased the formation of the diazepam
metabolite oxazepam, but only the extract, the drug powder and the pure compounds had
marked effects. Therefore, we report here the potential interference of St. John´s Wort
with all three metabolites of diazepam in an organotypical sandwich model that can be
utilized to study potential interaction of metabolites of many drugs with herbal ingredients
in preclinical stage of drug discovery process.
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Keywords
In vitro model, pharmaceutical screening, primary porcine hepatocytes, drug-drug interactions, cytochrome P450, St. John’s Wort
Citation
Acikgöz Ali, Langsch Angelika, Bader Augustinus, Giri Shibashish. Potential Interactions of Herbal Extracts of St. John´s Wort with Metabolites of Diazepam in an Organotypical Sandwich Culture of Primary Porcine Hepatocytes. British Journal of Pharmaceutical Research. 2014 Aug; 4(15): 1840-1860.