Original Paper Pharmacology	Planta Med 2006; 72: 1366-1371 DOI: 10.1055/s-2006-951710
© Georg Thieme Verlag KG Stuttgart · New York
Effects of St. John's Wort Extract and Single Constituents on Stress-Induced Hyperthermia in Mice
Oliver Grundmann1, Olaf Kelber2, Veronika Butterweck1
1 Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA 2 Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany

Abstract

Emotional or stress-induced hyperthermia (SIH) is the rise of body temperature following exposure to psychological stress and has been demonstrated across species. In the present experiments we used exposure to an open field (OF) as inescapable stressor. Exposure of male BL6/C57J mice to OF stress significantly increased body temperature (ΔT = 1.8 ± 0.13 °C, p < 0.05). SIH is calculated as the difference (ΔT = T₂ - T₁) between the basal temperature (T₁) and the temperature after exposure to an OF for 10 min (T₂). Using this experimental design, St. John's wort extract (SJW) as well as various single compounds of it were tested for their ability to affect ΔT. Anxiolytic drugs (the benzodiazepine diazepam; 5 mg/kg, and the 5HT_1A receptor agonist buspirone; 10 mg/kg) significantly reduced ΔT, whereas antidepressants (imipramine and fluoxetine) had no effect on ΔT. Oral administration of SJW extract significantly reduced ΔT in doses of 250 and 500 mg/kg. Higher (750 and 1000 mg/kg) as well as a lower dose (125 mg/kg) did not affect ΔT after stress, indicating a U-shaped dose-response curve. Hypericin (0.1 mg/kg, p. o.) administered 60 min prior to testing significantly decreased ΔT (p < 0.05) whereas hyperforin (1 - 10 mg/kg, p. o.) had no effect in this test paradigm. The flavonoids hyperoside, isoquercitrin and quercitrin (all at 0.6 mg/kg, p. o.) and rutin (1 mg/kg, p. o.) only partially blocked OF-induced hyperthermia. If compared to all other flavonoids, the quercetin 3-O-glucuronide miquelianin (1.2 mg/kg, p. o.) was the most potent compound tested in this experimental design. From the biflavonoids in SJW, only amentoflavone decreased SIH-induced hyperthermia in a dosage of 0.1 mg/kg. In conclusion, using open field stress as a psychological stressor to induce hyperthermia in mice we were able to detect putative anxiolytic effects of SJW extract and single consituents.

Abbreviations

ANOVA:analysis of variance

GABA:γ-amino-butyric acid

5-HT:5-hydroxytryptamine

OF:open field

SIH:stress-induced hyperthermia

SJW:St. John's wort

Key words

St. John's wort - hyperforin - hypericin - flavonoids - stress-induced hyperthermia - anxiolytic