Planta Med 2005; 71(7): 592-598
DOI: 10.1055/s-2005-871262
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Preserved Pharmacological Activity of Hepatocytes-Treated Extracts of Valerian and St. John's Wort

Urs Simmen1 , Caroline Saladin1 , Priska Kaufmann2 , Manisha Poddar2 , Christine Wallimann1 , Willi Schaffner1
  • 1Institute of Pharmaceutical Biology, University of Basel, Basel, Switzerland
  • 2Department of Clinical Pharmacology and Toxicology and Department of Research, University Hospital of Basel, Basel, Switzerland
Further Information

Publication History

Received: September 1, 2004

Accepted: January 3, 2005

Publication Date:
18 July 2005 (online)

Abstract

The two herbal extracts valerian (Valeriana officinalis L.) and St. John’s wort (Hypericum perforatum L.) were studied for their metabolic changes upon incubation with freshly prepared rat hepatocytes and subsequently analysed phytochemically as well as pharmacologically in vitro. Quantitative HPLC analysis of valerian extracts revealed considerable metabolic activities with regard to sesquiterpenes and iridoids. The amount of acetoxyvalerenic acid decreased 9-fold, while that of hydroxyvalerenic acid correspondingly increased 9-fold due to O-deacetylation. The valepotriates didrovaltrate, isovaltrate and valtrate decreased 2-, 18- and 16-fold, respectively. However, the binding affinities of the incubated extracts to the benzodiazepine and picrotoxin binding site of the GABAA receptor were quite similar to those of the non-incubated extracts. Neither valerenic acids nor valepotriates exhibited any significant effect on the two binding sites when tested as single compounds. Therefore, either other constituents represent the active ones or multiple compounds are necessary for the observed inhibitory and allosteric effects at the GABAA receptor. Extracts of St. John’s wort were less potently metabolised than valerian. The amount of pseudohypericin and the main flavonoids (hyperoside, rutin, isoquercitrin, quercitrin, quercetin and I3,II8-biapigenin) slightly decreased during the 4-h incubation period. Both the antagonist effect at the corticotropin-releasing factor (CRF) type 1 receptor and the binding inhibition at the 5-HT transporter were attenuated during the metabolic treatment. The reduced antagonist effect correlates with the decreasing amount of pseudohypericin known to be a CRF1 receptor antagonist. In conclusion, the incubation of plant extracts with freshly prepared rat hepatocytes represents a useful approach to study the pharmacological action of metabolised plant extracts. The consistent pharmacological activity of both valerian and St. John’s wort is concordant with the known clinical efficacy of pharmacological activities.

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Dr. Urs Simmen

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Email: usimmen@dtc.ch