Skip to content
Research Article Open access CC BY 3.0

Potential Interactions of Herbal Extracts of St. John´s Wort with Metabolites of Diazepam in an Organotypical Sandwich Culture of Primary Porcine Hepatocytes

Ali Acikgöz, Angelika Langsch, Augustinus Bader, Shibashish Giri

Journal of Pharmaceutical Research International · pp. 1840–1860 · Published 1 Aug 2014

10.9734/BJPR/2014/9602

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.

In vitro model pharmaceutical screening primary porcine hepatocytes drug-drug interactions, cytochrome P450; St. John’s Wort

References (18)

  1. 1 St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor [DOI]
  2. 2 Indinavir concentrations and St John's wort [DOI]
  3. 3 Identification of a human nuclear receptor defines a new signaling pathway for CYP 3 A induction [DOI]
  4. 4 Acute heart transplant rejection due to Saint John's wort [DOI]
  5. 5 Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation. [DOI]
  6. 6 Culture matrix configuration and composition in the maintenance of hepatocyte polarity and function [DOI]
  7. 7 P-glycoprotein Expression, Localization, and Function in Sandwich-Cultured Primary Rat and Human Hepatocytes: Relevance to the Hepatobiliary Disposition of a Model Opioid Peptide [DOI]
  8. 8 St John's wort, a herbal antidepressant, activates the steroid X receptor [DOI]
  9. 9 Oral Bioavailability of Hyperforin from Hypericum Extracts in Rats and Human Volunteers [DOI]
  10. 10 Interaction of Hypericum perforatum (St. John's wort) with cyclosporin A metabolism in a patient after liver transplantation [DOI]
  11. 11 Evaluation of the effect of culture configuration on morphology, survival time, antioxidant status and metabolic capacities of cultured rat hepatocytes [DOI]
  12. 12 EROD and MROD as Markers of Cytochrome P450 1A Activities in Hepatic Microsomes from Entire and Castrated Male Pigs [DOI]
  13. 13 Safety of St John's wort (Hypericum perforatum) [DOI]
  14. 14 Influence of Extracellular Matrix Overlay on Phenobarbital-Mediated Induction of CYP2B1, 2B2, and 3A1 Genes in Primary Adult Rat Hepatocyte Culture [DOI]
  15. 15 Interaction of St John's wort with conventional drugs: systematic review of clinical trials [DOI]
  16. 16 Phenobarbital responsiveness as a uniquely sensitive indicator of hepatocyte differentiation status: requirement of dexamethasone and extracellular matrix in establishing the functional integrity of cultured primary rat hepatocytes [DOI]
  17. 17 Preclinical characterization of primary porcine hepatocytes in a clinically relevant flat membrane bioreactor [DOI]
  18. 18 The use of in vitro metabolism studies in the understanding of new drugs [DOI]

Cited by 0

No indexed citations yet.

Article metrics

Real usage data collected on this platform.

13

Page views

0

PDF downloads

1

Outbound clicks

0

Citations

Views over time

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

Traffic sources

Referring site, by host.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.