|1: Planta Med. 2004 Oct;70(10):1008-11.
Flavonoids of St. John's Wort reduce HPA axis function in the rat.
Butterweck V, Hegger M, Winterhoff H.
Department of Pharmaceutics, University of Florida, Gainesville, FL 32610,
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 , whereas the phloroglucinol derivative hyperforin was inactive
in the same model . 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.
PMID: 15490333 [PubMed - indexed for MEDLINE]