RATIONALE: Hyperforin has been identified as an active constituent of Hypericum perforatum but its importance in the antidepressant effect of this plant's extracts is not really known. OBJECTIVE: To evaluate the antidepressant-like activity of two extracts in relation to the content of hyperforin and its plasma and whole brain concentrations, compared with a stable salt of hyperforin (dicyclohexylammonium; DCHA). METHODS: The effects of the extracts and hyperforin were evaluated in the rat forced swimming test. The specificity of the effects was demonstrated evaluating the rats' locomotor activity. Plasma and brain concentrations of hyperforin were determined by high performance liquid chromatography. RESULTS: The 4.5% extract (but not the 0.5% extract) given as three IP injections in 24 h (3.12-6.25 mg/kg) reduced the total immobility of rats, yielding dose-related plasma concentrations of hyperforin. These concentrations were of a similar magnitude to those after hyperforin DCHA which also significantly reduced immobility when given on the basis of the hyperforin content of the 4.5% extract (0.14 and 0.28 mg/kg). However, hyperforin was undetectable in rat brain, possibly because of poor passage of the blood-brain barrier. CONCLUSION: These results support the view that hyperforin plays a key role in the antidepressant-like activity of Hypericum p. However, brain concentrations after effective doses are probably far from those active in vitro on the neurotransmitter mechanisms so far investigated.
RATIONALE: Hyperforin has been identified as an active constituent of Hypericum perforatum but its importance in the antidepressant effect of this plant's extracts is not really known. OBJECTIVE: To evaluate the antidepressant-like activity of two extracts in relation to the content of hyperforin and its plasma and whole brain concentrations, compared with a stable salt of hyperforin (dicyclohexylammonium; DCHA). METHODS: The effects of the extracts and hyperforin were evaluated in the rat forced swimming test. The specificity of the effects was demonstrated evaluating the rats' locomotor activity. Plasma and brain concentrations of hyperforin were determined by high performance liquid chromatography. RESULTS: The 4.5% extract (but not the 0.5% extract) given as three IP injections in 24 h (3.12-6.25 mg/kg) reduced the total immobility of rats, yielding dose-related plasma concentrations of hyperforin. These concentrations were of a similar magnitude to those after hyperforinDCHA which also significantly reduced immobility when given on the basis of the hyperforin content of the 4.5% extract (0.14 and 0.28 mg/kg). However, hyperforin was undetectable in rat brain, possibly because of poor passage of the blood-brain barrier. CONCLUSION: These results support the view that hyperforin plays a key role in the antidepressant-like activity of Hypericum p. However, brain concentrations after effective doses are probably far from those active in vitro on the neurotransmitter mechanisms so far investigated.