Planta Med 2004; 70(10): 1008-1011
DOI: 10.1055/s-2004-832631
Letter
© Georg Thieme Verlag KG Stuttgart · New York

Flavonoids of St. John’s Wort Reduce HPA Axis Function in the Rat

V. Butterweck1 , M. Hegger2 , H. Winterhoff2
  • 1Department of Pharmaceutics, University of Florida, Gainesville, FL, USA
  • 2Institute of Pharmacology and Toxicology, Münster, Germany
Further Information

Publication History

Received: April 26, 2004

Accepted: July 26, 2004

Publication Date:
18 October 2004 (online)

Abstract

A common biological alteration in patients with major depression is the activation of the hypothalamic-pituitary-adrenal (HPA) axis, manifested as hypersecretion of adrenocorticotropic hormone (ACTH) and cortisol. The hyperactivity of the HPA axis in depressed patients can be corrected during clinically effective therapy with standard antidepressant drugs such as imipramine, indicating that the HPA axis may be an important target for antidepressant action. We previously showed that a methanolic extract of St. John’s wort (SJW) and hypericin, one of its active constituents, both have delayed effects on the expression of genes that are involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis [1], whereas the phloroglucinol derivative hyperforin was inactive in the same model [2]. Since flavonoids of SJW are also discussed as active constituents it was of interest to determine whether these compounds can modulate HPA axis function. Imipramine (15 mg/kg), hypericin (0.2 mg/kg), hyperoside (0.6 mg/kg), isoquercitrin (0.6 mg/kg) and miquelianin (0.6 mg/kg) given daily by gavage for two weeks significantly down-regulated circulating plasma levels of ACTH and corticosterone by 40 - 70 %. However, none of the compounds tested had an effect on plasma ACTH and corticosterone levels after chronic treatment (daily gavage for 8 weeks). Our data suggest that besides hypericin, flavonoids of SJW play an important role in the modulation of HPA axis function. Furthermore, the results support the hypothesis that flavonoids are involved in the antidepressant effects of SJW.

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Dr. Veronika Butterweck

Department of Pharmaceutics

University of Florida

PO Box 100494

Gainesville

FL 32610

USA

Phone: +1-352-846-2470

Fax: +1-352-392-4447

Email: butterwk@cop.ufl.edu

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