Hypericum perforatum is considered an effective alternative to the synthetic antidepressants in the treatment
of mild-to-moderate depression. Recently, we showed that the effects on neurotransmitter
contents in different brain regions of laboratory animals are more evident after administration
of hypericum extracts containing a higher concentration of flavonoids, thus suggesting
that these compounds are important in the antidepressant action of hypericum perforatum. We studied the effects of Ph-50, a hypericum extract standardized to flavonoids
(50 %) and containing 0.3 % hypericin and 4.5 % hyperforin on brain serotonin content,
norepinephrine and dopamine by a high-performance liquid chromatography method in
discrete brain areas (cortex, diencephalon and brainstem) in male Sprague-Dawley rats.
Moreover, we evaluated the effects of Ph-50 alone or in association with sulpiride
(a dopamine receptor antagonist), metergoline (a serotonin receptor antagonist) and
6-hydroxydopamine (6-OH-DA, destroying norepinephrine-containing neurons) using a
forced-swimming test in the rat. Hypericum extract (Ph-50; 250 - 500 mg/kg) with acute
oral administration enhanced serotonin, norepinephrine and dopamine content in the
brain and reduced the immobility time of rats in the forced-swimming test. Sulpiride,
metergoline and 6-OH-DA significantly increased the period of immobility in the forced-swimming
test for the rats receiving hypericum extract (Ph-50). The results indicate that the
neurotransmitters studied could be involved in the anti-immobility effects of hypericum,
and suggest that its antidepressant action is probably mediated by serotonergic, noradrenergic
and dopaminergic system activation.
References
- 1
Bladt S, Wagner H.
Inhibition of MAO by fractions and constituents of hypericum extract.
J Geriatric Psychiatr Neurol.
1994;
7
57-59
- 2
Bennett D A, Phun L, Polk J F, Voglino S A, Zlotnik V, Raffa R B.
Neuropharmacology of St-John's Wort (Hypericum).
Ann Pharmacother.
1998;
32
1201-1208
- 3
Butterweck V, Wall A, Lieflander-Wulf L, Winterhoff H, Nahrstedt A.
Effects of the total extract and fractions of hypericum perforatum in animal assays
for antidepressant activity.
Pharmacopsychiatry.
1997;
30
(Suppl. 2)
117-124
- 4
Calapai G, Crupi A, Firenzuoli F, Inferrera G, Campo G M, Caputi A P.
Effects of hypericum perforatum on levels of 5-Hydroxytryptamine. Noradrenaline and
Dopamine in the cortex, diencephalon and brainstem of the rat.
J Pharm Pharmacol.
1999;
51
723-728
- 5
Calapai G, Corica F, Corsonello A, Sautebin L, Di Rosa M, Campo G M, Buemi M, Nicita
Mauro V, Caputi A P.
Leptin increases serotonin turnover by inhibition of brain nitric oxide synthesis.
J Clin Invest.
1999;
104
975-982
- 6
Cervo L, Grignaschi G, Rossi C, Samanin R.
Role of central serotonergic neurons in the effect of sertraline in rats in the forced
swimming test.
Eur J Pharmacol.
1991;
196
217-222
- 7
Cott J M.
In vitro receptor binding and enzyme inhibition by hypericum perforatum extract.
Pharmacopsychiatry.
1997;
30
(Suppl. 2)
108-112
- 8
Delgado P, Moreno F.
Antidepressants and the brain.
Int din Psychopharmacol.
1999;
1
(Suppl. 14)
9-16
- 9
De Saint Blanquat G, Lambouef Y, Fritsch P.
Determination of catecholamines in biological tissues by liquid chromatography with
coulometric detection.
fehlt.
1987;
415
388-392
- 10
Gobbi M, Dallavalle F, Ciapparelli C, Diomede L, Morazzoni P, Verotta L, Caccia S,
Cervo L, Mennini T.
Hypericum perforatum L. extract does not inhibit 5-HT transporter in rat brain cortex.
Naunyn-Shmiedeberg's Archives of Pharmacology.
1999;
360
262-269
- 11
Grimaldi B, Bonnin A, Fillion M P, Prudhomme N, Fillion G.
5-Hydroxytriptamine-moduline: a novel endogenous peptide involved in the control of
anxiety.
Neuroscience.
1999;
93
1223-1225
- 12
Hantraye P.
Modeling dopamine system dysfunction in experimental animals.
Nucl Med Biol.
1998;
25
721-728
- 13
Hank S L.
Locus coeruleus lesion by local 6-hydroxydopamine infusion causes marked and specific
destruction of noradrenergic neurons, long-term depletion of norepinephrine and the
enzymes that synthesize it, and enhanced dopaminergic mechanisms in the ipsilateral
cerebral cortex.
J Neurosci.
1984;
4
699-707
- 14
Harrer G, Schulz V.
Clinical investigation of the antidepressant effectiveness of hypericum.
J Geriatr Psychiatry Neurol.
1994;
7
(Suppl. 1)
6-8
- 15
Heinz A, Schmidt L G, Reischies F M.
Anhedonia in schizophrenic, depressed, or alcohol-dependent patients-neurobiological
correlates.
Pharmacopsychiatry.
1994;
27
(Suppl. 1)
7-10
- 16
Josey E S, Tackett R L.
St John's wort: a new alternative for depression?.
Int J Clin Pharmacol Ther.
1999;
37
111-119
- 17
Kasper S.
From symptoms to social functioning: differential effects of antidepressant therapy.
Int Clin Psychopharmacol.
1999;
14
27-31
- 18
Leonard B E.
Mechanisms of action of antidepressants.
CNS Drugs.
1995;
4
(Suppl. 1)
1-12
- 19
Linde K, Ramirez G, Mulrow C D, Pauls A, Weidenhammer W, Melchart D.
St John's wort for depression - an overview and meta-analysis of randomized clinical
trials.
Brit Med J.
1996;
313
253-258
- 20
Lookmann G, Schille C, Baghal T, Kleser M.
St. John's Wort in mild to moderate depression: the relevance of hyperforin for the
clinical efficacy.
Pharmacopsychiatry.
1998;
31
54-59
- 21
Lucki I.
The forced-swimming test as a model for core and component behavioral effects of antidepressant
drugs.
Behav Pharmacol.
1997;
8
523-532
- 22
Montgomery S A.
Predicting response: norepinephrine reuptake inhibition.
Int Clin Psychopharmacol.
1999;
I
(Suppl. 14)
21-26
- 23
Muller W E, Kasper S.
Clinically used antidepressant drugs.
Pharmacopsychiatry.
1997;
2
(Suppl. 30)
71
- 24
Muller W E, Rolli M, Schafer C, Hafner U.
Effects of hypericum extract (Li 160) in biochemical models of antidepressant activity.
Pharmacopsychiatry.
1997;
30
(Suppl. 2)
102-107
- 25
Muller W E, Singer A, Wonnemann M, Hafner U, Rolli M, Schafer C.
Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum
extract.
Pharmacopsychiatry.
1998;
31
(Suppl. 1)
16-21
- 26
Nathan P.
The experimental and clinical pharmacology of St. John's Wort (Hypericum perforatum
L.)
Mol. Psychiatry.
1999;
4
333
- 27 Paxinos F, Watson C. The Rat Brain in Stereotaxic Coordinates. Academic Press London
1986
- 28
Porsolt R D, Anton G, Blavet N, Jafre M.
Behavioral despair in rats: A new model sensitive to antidepressant.
Eur J Pharmacol.
1978;
47
379-391
- 29
Squadrito F, Calapai G, Altavilla D, Cucinotta D, Zingarelli B, Arcoraci V, Campo G M,
Capuli A P.
Central serotonergic system involvement in the anorexia induced by NG nitro-L-arginine, an inhibitor of nitric oxide synthase.
Eur J Pharmacol.
1994;
255
51
- 30
Suzuki O, Katsumata Y, Oya M, Bladt S, Wagner H.
Inhibition of monoamine oxidase by hypericin.
Planta Med.
1984;
50
272-274
- 31
Vitiello B.
Hypericum perforatum extracts as potential antidepressants.
J Pharm Pharmacol.
1999;
51
513-517
- 32
Volz H P.
Controlled clinical trials of hypericum extracts in depressed patients - an overview.
Pharmacopsychiatry.
1997;
2
(Suppl. 2)
72-76
- 33
Wheatley D.
Li 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately
depressed outpatients - a controlled 6-week clinical trial.
Pharmacopsychiatry.
1997;
2
(Suppl. 30)
77
- 34
Wheatley D.
Hypericum extract-Potential in the treatment of depression.
CNS Drugs.
1998;
9
431-440
- 35
Wheatly P.
Hypericum in seasonal affective disorder (SAD).
Curr Med Opin.
1999 a;
15
33-37
- 36
Willner P.
The mesolimbic dopamine system as a target for rapid antidepressant action.
Int Clin Psychopharmacol.
1997;
3
(Suppl. 12)
7-14
- 37
Zuardi A W.
5-HT related drugs and human experimental anxiety.
Neurosci Biobehav Rev.
1990;
14
507-510
Gioacchino Calapai, MD
Institute of Pharmacology
School of Medicine, University of Messina
Via Consolare Valeria 49
Policlinico Universitario - Torre Biologica 5° Piano
98124 - Messina
Italy
Phone: 090/2213646
Fax: 090/2213300
Email: gcalapai@unime.it
