TITLE: St John's wort for depression-
-an overview and meta-analysis of randomised clinical trials
[see comments]

AUTHOR: Linde K; Ramirez G; Mulrow CD; Pauls A;
Weidenhammer W; Melchart D
AUTHOR AFFILIATION: Projekt Munchener Modell,
Ludwig-Maximilians-Universitat, Munich, Germany.

SOURCE: BMJ 1996 Aug 3;313(7052):253-8
NLM CIT. ID: 96322668
COMMENT: BMJ 1996 Aug 3;313(7052):241-2
BMJ 1996 Nov 9;313(7066):1204-5 

ABSTRACT: OBJECTIVE--To investigate if extracts of
Hypericum perforatum (St John's wort) are more effective
than placebo in the treatment of depression, are as effective
as standard antidepressive treatment, and have fewer side effects
than standard antidepressant drugs.
DESIGN--Systematic review and meta-analysis of trials
revealed by searches.
TRIALS--23 randomised trials including
a total of 1757 outpatients with mainly mild
or moderately severe depressive disorders:
15 (14 testing single preparations and one a
combination with other plant extracts)
were placebo controlled, and eight
(six testing single preparations and two combinations)
compared hypericum with another drug treatment.
MAIN OUTCOME MEASURES--
A pooled estimate of the responder rate ratio
(responder rate in treatment group/responder rate in control group),
and numbers of patients reporting and dropping out for side effects.
RESULTS--Hypericum extracts were significantly superior to
placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01)
and similarly effective as standard antidepressants
(single preparations 1.10; 0.93 to 1.31,
combinations 1.52; 0.78 to 2.94).
There were two (0.8%) drop outs for side effects with hypericum
and seven (3.0%) with standard antidepressant drugs.
Side effects occurred in 50 (19.8%) patients on hypericum
and 84 (52.8%) patients on standard antidepressants.
CONCLUSION--There is evidence that extracts of hypericum are more
effective than placebo for the treatment of mild to moderately
severe depressive disorders. Further studies comparing extracts
with standard antidepressants in well defined groups of patients
and comparing different extracts and doses are needed.



TITLE: Controlled clinical trials
of hypericum extracts in
depressed patients--an overview.

AUTHOR: Volz HP
AUTHOR AFFILIATION: Psychiatric Department,
University of Jena, Germany.

SOURCE: Pharmacopsychiatry 1997 Sep;30 Suppl 2:72-6
NLM CIT. ID: 98002170

ABSTRACT: In Germany, hypericum extracts are among
the most widely prescribed antidepressants.
Additionally, many preparations of St. John's wort
are sold on the free market and one extract is even
the best selling antidepressant in the country.
In contrast to synthetic antidepressants,
the approval procedures are not so strict,
which implies that the pharmaceutical industry
is not forced to conduct clinical trials suitable for licensing.
Nevertheless, numerous studies on hypericum extracts
including depressed patients have been published
in the last 20 years.
The purpose of this paper is to review these investigations
in respect of methodological considerations
and to draw conclusions pertaining to the proof
of antidepressant efficacy. To this effect,
a computer-assisted literature research
was performed and manufacturers were asked
to supply the author with study results.
A total of 12 placebo-controlled trials
with hypericum extracts were performed,
mostly with positive results.
Also in comparison with synthetic antidepressants
(3 studies published), a similar reduction of depressive
symptomatology was seen,
although the comparators were not adequately dosed.
No trials in severely depressed patients have been published yet.
Since most studies on hypericum have methodological flaws,
further studies are warranted.


TITLE: Treatment of seasonal affective disorder (SAD)
with hypericum extract.

AUTHOR: Kasper S
AUTHOR AFFILIATION: Department of General Psychiatry,
University of Vienna, Austria.

SOURCE: Pharmacopsychiatry 1997 Sep;30 Suppl 2:89-93
NLM CIT. ID: 98002174

ABSTRACT: Seasonal affective disorder (SAD)
is a subgroup of major depression and characterized
by a regular occurrence of symptoms in autumn/winter
and full remission or hypomania in spring/summer.
Light therapy (LT) and recently pharmacotherapy
with specific antidepressants have been shown to be beneficial.
Within the array of pharmacotherapy hypericum extract
has also been found to be effective in a single-blind study
(Martinez et al., 1994).
In this 4 weeks treatment study 900 mg of hypericum
was associated with a significant reduction
in the total score of the Hamilton Depression Rating Scale.
There was no significant difference when bright light therapy
was combined with hypericum,
compared to the situation without bright light therapy.
Overall, hypericum was well tolerated
and therefore the data suggest that
pharmacological treatment with hypericum
may be an efficient therapy in patients with SAD,
which needs to be substantiated in further controlled studies.


TITLE: LI 160, an extract of St. John's wort,
versus amitriptyline in mildly to moderately depressed 
outpatients--a controlled 6-week clinical trial.

AUTHOR: Wheatley D
AUTHOR AFFILIATION: Department of Psychological Medicine,
Royal Masonic Hospital, London, UK.

SOURCE: Pharmacopsychiatry 1997 Sep;30 Suppl 2:77-80
NLM CIT. ID: 98002171

ABSTRACT: Up to now, the antidepressant efficacy
of the extract of St. John's wort, LI 160,
has been compared to imipramine and maprotiline,
demonstrating similar antidepressant efficacy
in mildly to moderately depressed patients,
treated either with LI 160
or the respective synthetic comparator.
In the study reported here, LI 160 (total daily dose: 900 mg)
was compared with the sedating tricyclic amitriptyline
(total daily dose: 75 mg)
in a controlled, randomized, multicentre trial.
At the end of the 6-week study, the major target variable,
the Hamilton Depression Scale response rate,
exhibited no statistically significant difference
between the groups,
although a tendency for a better response rate
was seen in the amitriptyline group.
The secondary efficacy parameters,
decreases in the total Hamilton Depression
and Montgomery-Asberg scores,
showed a significant advantage for amitriptyline,
but only at week 6.
With regard to tolerability,
LI 160 was clearly superior to amitriptyline,
particularly in relation to anticholinergic
and Central Nervous System adverse events.
Thus, 37% of the LI 160 treated patients
reported adverse events,
compared to 64% in the amitriptyline group.
This considerable superiority in tolerability
for LI 160 in relation to amitriptyline,
could confer an advantage in improving compliance
for antidepressant pharmacotherapy.


TITLE: Biologically active and other chemical constituents
of the herb of Hypericum perforatum L.

AUTHOR: Nahrstedt A; Butterweck V
AUTHOR AFFILIATION: Department of Pharmaceutical Biology
and Phytochemistry,
Westphalian Wilhelms University of Munster, Germany.

SOURCE: Pharmacopsychiatry 1997 Sep;30 Suppl 2:129-34
NLM CIT. ID: 98002181

ABSTRACT: Phenylpropanes, flavonol derivatives, biflavones,
proanthocyanidins, xanthones, phloroglucinols, some amino acids,
naphthodianthrones and essential oil constituents
are the natural plant products known
from the crude drug of Hypericum perforatum, Hyperici herba.
These compounds are discussed with respect to structural features,
their concentration, biological activities
and their possible contribution
to the clinically demonstrated antidepressant efficacy
of extracts obtained from Hyperici herba.


TITLE: Testing the antidepressant effects of
Hypericum species on animal models.

AUTHOR: Ozturk Y
AUTHOR AFFILIATION: Medicinal and Aromatic Plant
and Drug Research Centre,
Anadolu University, Eskisehir, Turkey.

SOURCE: Pharmacopsychiatry 1997 Sep;30 Suppl 2:125-8
NLM CIT. ID: 98002180

ABSTRACT: This paper summarizes
the antidepressant effects of certain Hypericum species
on animal models.
Although there are many drugs in clinical use
for the management of human depression,
most of the antidepressant drugs
have undesirable side effects,
some of which may limit the daily life of patients,
and therefore, more specific agents with lesser side effects
are necessary as a new therapeutic modality
for the rational treatment of depression.
In our laboratory, we observed antidepressant activity
with the alcoholic extract of H. calycinum
whose effects on the central nervous system of mice
are almost equal to the extract
prepared from St. John's wort, H. perforatum.
Other species, H. hyssopifolium ssp. elongatum var. elongatum
seems to have no antidepressant activity.
From these data, it can be concluded that at least some of
Hypericum species may have a potential use for the treatment
of depression.


TITLE: Inhibition of benzodiazepine binding in vitro
by amentoflavone, a constituent of various species of Hypericum.

AUTHOR: Baureithel KH; Buter KB; Engesser A; Burkard W; Schaffner W
AUTHOR AFFILIATION: Dept. of Pharmaceutical Biology,
University of Basel, Switzerland.

SOURCE: Pharm Acta Helv 1997 Jun;72(3):153-7
NLM CIT. ID: 97348835

ABSTRACT: Flower extracts of Hypericum perforatum,
Hypericum hirsutum, Hypericum patulum and Hypericum olympicum
efficiently inhibited binding of [3H]flumazenil
to rat brain benzodiazepine binding sites
of the GABAA-receptor in vitro
with IC50 values of
6.83, 6.97, 13.2 and 6.14 micrograms/ml, respectively.
Single constituents of the extracts like hypericin,
the flavones quercetin and luteolin,
the glycosylated flavonoides rutin, hyperoside and quercitrin
and the biflavone 13, II8-biapigenin
did not inhibit binding up to concentrations of 1 microM.
In contrast, amentoflavone revealed an IC50 = 14.9 +/- 1.9 nM
on benzodiazepine binding in vitro.
Comparative HPLC analyses of hypericin
and amentoflavone in extracts of different Hypericum species
revealed a possible correlation between
the amentoflavone concentration and the
inhibition of flumazenil binding.
For hypericin no such correlation was observed.
Our experimental data demonstrate that amentoflavone,
in contrast to hypericin,
presents a very active compound
with regard to
the inhibition of [3H]-flumazenil binding in vitro
and thus might be involved in the antidepressant effects
of Hypericum perforatum extracts.


TITLE: [St John's wort against depression in favour again]

AUTHOR: Nordfors M; Hartvig P
AUTHOR AFFILIATION: Sodra Stockholms sjukv~ardsomr~ade.

SOURCE: Lakartidningen 1997 Jun 18;94(25):2365-7
NLM CIT. ID: 97359231

ABSTRACT: Extracts of Hypericum perforatum
St. John's wort, have been used since antiquity
for the treatment of depressive symptoms.
In 25 controlled clinical trials
where hypericum extract was compared with placebo
and established antidepressants,
improvement was obtained in 61 percent of patients
on low-dose treatment (< 1.2 mg hypericum extract),
and in 75 percent of patients treated
with a higher dose (2.7 mg).
The side effects were mild and occurred at lower frequency
than did those of other antidepressants.
The constituent of hypericum extract
that is responsible for the antidepressant effect
has not been identified.
Nor is the mechanism of action known,
but a combination of low-grade monoamine oxidase inhibition
and noradrenaline and serotonin reuptake blockade
seems the most likely alternative,
though other interesting mechanisms
have also been proposed.
Owing to their beneficial effect and low toxicity,
preparations containing extracts from H perforatum
might furnish an alternative to established therapy,
especially among patients concerned about stigmatization
or less apprehensive of herbal medication
than of synthetic drugs.



TITLE: The effect of hypericum extract
on cardiac conduction as seen in the electrocardiogram
compared to that of imipramine.

AUTHOR: Czekalla J; Gastpar M; Hubner WD; Jager D
AUTHOR AFFILIATION: Department of General Psychiatry,
ECG Laboratory, University Clinic, Essen, Germany.

SOURCE: Pharmacopsychiatry 1997 Sep;30 Suppl 2:86-8
NLM CIT. ID: 98002173

ABSTRACT: The electrocardiographic effects
of high-dose hypericum extract were compared
to the effects of imipramine hydrochloride on ECG recordings
in a randomized, double-blind, multicenter treatment study
of 209 patients suffering from depression.
ECGs were recorded before and after a six-week treatment period
with either hypericum extract or imipramine.
At the end of the study ECGs of 84 patients
treated with hypericum extract
and 76 patients treated with imipramine
were suitable for an analysis of conduction intervals
and pathological findings.
In the first ECG analysis
comparing high dose hypericum extract with imipramine,
a prolongation of the conduction intervals PR, QRS and QTc
was found for imipramine. In contrast,
a small acceleration of conduction was seen
for the high-dose hypericum extract.
The comparison of ECGs at the beginning
and after six weeks of treatment
showed a significant increase in first degree AV-blocks
and abnormalities of repolarization under imipramine
but a significant reduction of such pathological findings
under treatment with hypericum extract.
It should be emphasized that this favorable feature
of safe cardiac activity was achieved with
1800 mg of hypericum extract.
The reduction in pathological ECG features
after treatment with hypericum extract
may have resulted mainly from the change of medication,
probably tricyclics, to hypericum extract.
Our results indicate that for the treatment of patients
with a pre-existing conductive dysfunction
or elderly patients,
high-dose hypericum extract is safer
with regard to cardiac function
than tricyclic antidepressants.


TITLE: [Antioxidant properties of
a series of extracts from medicinal plants]

AUTHOR: Bol'shakova IV; Lozovskaia EL; Sapezhinskii II

SOURCE: Biofizika 1997 Mar-Apr;42(2):480-3
NLM CIT. ID: 97274773

ABSTRACT: Investigation of antioxidant properties
of some plants was carried out.
A group of plants affected human central nervous system
was studied in detail.
Efficiency of plants as antioxidants
was tested by the influence of their extracts
on the yield of photochemiluminescence of Gly-Trp solutions.
Antioxidant properties were examined
under conditions when their own absorption was minimized.
Riboflavin as additional sensitizer
was used in this experiment for superoxide generation.
The antioxidant effect was evaluated
with regard to single dose of plant extracts
and their concentration in human organism.
The effect decreases in the following consequence:
Hypericum > Eleutherococcus > Rhodiola >
Leonurus > Aralia > Valeriana > Echinopanax >
Schizandra > Panax gin-seng.


TITLE: Pharmacological profile of hypericum extract.
Effect on serotonin uptake by postsynaptic receptors.

AUTHOR: Perovic S; Muller WE
AUTHOR AFFILIATION: Institut fur Physiologische Chemie,
Universitat Mainz, Germany.

SOURCE: Arzneimittelforschung 1995 Nov;45(11):1145-8
NLM CIT. ID: 96109447

ABSTRACT: In the present study it is reported that
the methanolic Hypericum extract LI 160 (Jarsin 300)
exerts no protective effect against N-methyl-D-aspartate (NMDA-)
or gp120- (from the HIV virus) induced cytotoxicity.
Moreover, it is established that Hypericum extract
causes no activation of arachidonic acid
release from neurons activated by gp120;
hence it displays no sensitization effect
on the NMDA receptor channel.
The main outcome of this study is the finding that
Hypericum extract causes a 50% inhibition (IC50 value)
of serotonin uptake by rat synaptosomes
at a concentration of 6.2 microglml.
Therefore it is concluded that
the antidepressant activity of Hypericum extract
is due to an inhibition of serotonin uptake
by postsynaptic receptors.
Future studies might focus on the effect of Hypericum extract
on serotonin binding to neurons, serotonin storage in granules,
the rate of synthesis of serotonin,
and on the activity of monoamine oxidase.


TITLE: [The immunotropic properties of
biologically active products obtained from
Klamath weed (Hypericum perforatum L.)]

AUTHOR: Evstifeeva TA; Sibiriak SV

SOURCE: Eksp Klin Farmakol 1996 Jan-Feb;59(1):51-4
NLM CIT. ID: 96232885

ABSTRACT: We carried out a systematic study
of immunotropic activity of John's wort
on the level of integrated fractions
including all basic active substances of this plant.
Both types of substances capable
of increasing and suppressing the immunity
were found in John's wort.
Polyphenol fraction exhibits the immunostimulating activity
with respect to the system of mononuclear phagocyte system,
cellular and humoral immunity,
and is capable of recovering the immune response
in conditions of high-zone tolerance.
Lipophilic fraction of this plant
exhibits immunosuppressing properties with respect to
cellular and humoral immune response.
Immunotropic activity of polyphenol and lipophilic fractions
correlate with their low toxicity.



TITLE: Antibacterial phloroglucinols and flavonoids
from Hypericum brasiliense.

AUTHOR: Rocha L; Marston A; Potterat O; Kaplan MA;
Stoeckli-Evans H; Hostettmann K
AUTHOR AFFILIATION: Institut de Pharmacognosie et Phytochimie,
Universite de Lausanne, Lausanne-Dorigny, Switzerland.

SOURCE: Phytochemistry 1995 Nov;40(5):1447-52



TITLE: [Treatment of depressive symptoms
with a high concentration hypericum preparation.
A multicenter placebo-controlled double-blind study]

AUTHOR: Witte B; Harrer G; Kaptan T; Podzuweit H; Schmidt
UAUTHOR AFFILIATION: Arbeits- und Forschungsgemeinschaft
fur Arzneimittel-Sicherheit e. V., Koln.

SOURCE: Fortschr Med 1995 Oct 10;113(28):404-8
NLM CIT. ID: 96058894

ABSTRACT:
In a multicenter, placebo-controlled double-blind trial,
the effect on depression (ICD 10 F 32.1)
of treatment with an innovative highly concentrated
hypericum preparation was investigated.
The study contained 97 outpatients
who received 100 to 120 mg of the hypericum extract bid.
The course of the illness was assessed with
the Hamilton Depression Scale (HAMD),
the von Zerssen Depressivity Scale (D-S)
and the Clinical Global Impression Scale (CGIS).
Treatment resulted in an appreciable improvement
in the symptoms of depression,
and the 70% response rate (n = 43),
corresponded to that of chemical antidepressants.
The preparation also showed an anxiolytic effect.
The substance was extremely well tolerated,
and no side-effects were reported by any of the patients.


TITLE: Novel therapeutic and diagnostic
applications of hypocrellins and hypericins.

AUTHOR: Diwu Z
AUTHOR AFFILIATION: Molecular Probes, Inc.,
Eugene, OR 97402, USA.

SOURCE: Photochem Photobiol 1995 Jun;61(6):529-39
NLM CIT. ID: 96044410

ABSTRACT: Hypocrellins and hypericins,
structurally related plant pigments
isolated from Hypocrella bambuase and Hypericum respectively,
are known photodynamic agents.
This review summarizes certain significant advances
in the photophysics, photochemistry and photobiology
of these pigments in the last 2 years
and discusses their prospects as novel therapeutic
and diagnostic agents in the future.
Recently, certain unique properties
of hypocrellins and hypericins
have been explored for a variety of therapeutic
and diagnostic applications.
In particular, substantial progress
has been made in both anticancer
and antiviral applications
(especially anti-human immunodeficiency virus).
The promising anticancer and antiviral results
obtained both in vitro and in vivo
have led to intensive investigation
into their photo-physical and photochemical processes,
especially kinetic studies
of their intramolecular proton transfer.
These compounds offer the potential
for a highly sensitive fluorescent redox sensor
for investigation of a variety of cellular events.
The biomedical advances of hypocrellins and hypericins
have been further promoted by significant progress
in their chemical synthesis
and the recent commercialization
of hypocrellins A and B and hypericin.


TITLE: Antibacterial phloroglucinols and flavonoids
from Hypericum brasiliense.

AUTHOR: Rocha L; Marston A; Potterat O; Kaplan MA;
Stoeckli-Evans H; Hostettmann K
AUTHOR AFFILIATION: Institut de Pharmacognosie et Phytochimie,
Universite de Lausanne, Lausanne-Dorigny, Switzerland.

SOURCE: Phytochemistry 1995 Nov;40(5):1447-5