St. John's Worth

St. John’s
Wort
Hypericum
peforatum
Brief description
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St John’s wort is the plant species Hypericum perforatum, also
known as Tipton's Weed or Klamath weed, but, with qualifiers, is
used to refer to any species of the genus Hypericum. Therefore,
H. perforatum is sometimes called Common St John's wort to
differentiate it.
Approximately 370 species of the genus Hypericum exist
worldwide with a native geographical distribution including
temperate and subtropical regions of North America, Europe,
Asia Minor, Russia, India, and China. St. John's wort is today
most widely known as an herbal treatment for depression. They
are similarly effective as standard antidepressants and have
fewer side effects than these.
St John’s wort also can be useful in the treatment of alcoholism
and may has antibacterial properties (against gram negative
bacterias) and it might alliviate the symptoms of attention deficit
hiperactivity disorder.
Scientific classification
Kingdom
Plantae
Division
Magnoliophyta
Class
Magnoliopsida
Order
Malpighiales
Family
Clusiaceae
Genus
Hypericum
Species
Hypericum
perforatum
The plant
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Hypericum perforatum is a yellow-flowering, stoloniferous or
sarmentose, perennial herb indigenous to Europe, which has been
introduced to many temperate areas of the world and grows wild in
many meadows.
The common name comes from its traditional flowering and harvesting
on St John’s day, 24 of June.
The species name perforatum refers to the presence of small oil
glands in the leaves that look like windows, which can be seen when
they are held against the light.
In pastures, St John’s wort acts as both a toxic and invasive weed. It
replaces useful vegetation to the extent of making productive land
unviable or acts as an alien species in natural ecosystems. Ingestion
by livestock can cause photosensitization, central nervous system
depression, spontaneous abortion, and can lead to death.
Botanical description
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St John’s wort can be visually recognized by
leaf and flower type. St John's wort is a
perennial plant with extensive, creeping
rhizomes.Its stems are erect, branched in
the upper section, and can grow to 1 m high.
It has opposing, stalkless, narrow, oblong
leaves which are 12 mm long or slightly
larger. The leaves are yellow-green in color,
with transparent dots throughout the tissue
and occasionally with a few black dots on the
lower surface. Its flowers measure up to
2.5 cm across, have five petals, and are
colored bright yellow with conspicuous black
dots. The flowers appear in broad cymes at
the ends of the upper branches. The sepals
are pointed, with glandular dots in the tissue.
There are many stamens, which are united
at the base into three bundles.
Key constituents, analysis and
pharmacokinetics
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Rubbing a bud or flower from the St John’s wort between the
fingers immediately creates a purple stain caused by certain
constituents of the plant: hypericin, pseudohypericin,
protohypericin, protopseudohypericin and
cyclopseudohypericin, all belonging to the group of
naphtodianthrones.
The qualitative and quantitative method of analysis is HPLC.
Hypericin and more important, hyperforin contribute to the
antidepressant activity of the whole extract.
The dried herbs and extract also contain significant amounts of
some very common plant constituents such as flavonoids
derivates, xanthone derivates, biflavones, procyanidines and a
volatile oil (not more than 1%)
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Hyperforin levels are at least
10 times higher than
hypericin levels both in
alcohol extracts and in the
blood plasma after oral dosis.
They both are stable in
plasma and their
pharmacokinetics are
proportional to the
administrated dose.
Hyperforin and hypericin
Medical uses
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St John's wort is today most widely known as an herbal
treatment for depression. In some countries, such as Germany,
it is commonly prescribed for mild depression, especially in
children, adolescents, and where cost is a concern.
Standardized extracts are generally available over the counter
however, in some countries a prescription is required. Extracts
are usually in tablet or capsule form, and also in teabags and
tinctures.
An analysis of 29 clinical trials with more than 5000 patients
was concluded that extracts of St. John's wort were superior to
placebo in patients with major depression. St. John's wort had
similar efficacy to standard antidepressants. The rate of side
effects was twice lower than for newer SSRI antidepressants
and five times lower than for older tricyclic antidepressants.
Medical uses
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However, The National Center for Complementary and
Alternative Medicine (NCCAM) and other NIH-affiliated
organizations hold that St John's wort has minimal or no effects
beyond placebo in the treatment of major depression. This
conclusion is based primarily on one trial with negative
outcome conducted by NCCAM.The authors of the study
themselves, as well as several others pointed out the low assay
sensitivity of this study, and how only limited conclusions can
be drawn from its results. NCCAM is currently studying the use
of St. John's wort in a wider spectrum of mood disorders,
including minor depression.
Pharmacology
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The exact mechanism by which St John's wort
functions is unclear and subject to conjecture. The St
John's wort mechanism is believed to involve
inhibition of serotonin (5-HT) reuptake, much like the
conventional selective serotonin reuptake inhibitor
(SSRI) antidepressants. The major active
antidepressive constituents in St John's wort are
thought to be hyperforin and hypericin, although
other biologically active constituents present, for
example, flavonoids and tannins, may also be
involved.
Adverse effects
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St John's wort is generally well tolerated, with an adverse effect
profile similar to placebo. The most common adverse effects
reported are gastrointestinal symptoms, dizziness, confusion,
tiredness and sedation.
St John's wort may rarely cause photosensitivity. This can lead
to visual sensitivity to light and to sunburns in situations that
would not normally cause them. Related to this, recent studies
concluded that the extract reacts with light, both visible and
ultraviolet, to produce free radicals, molecules that can damage
the cells of the body. These can react with vital proteins in the
eye which, if damaged, precipitate out causing cataracts.
Drug interactions
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St John's wort has been shown to cause multiple drug
interactions mainly through induction of the cytochrome P450
enzyme CYP3A4, but also CYP2C9. This results in the
increased metabolism of those drugs, resulting in decreased
concentration and clinical effect. The principal constituent
thought to be responsible is hyperforin. Some of the class of
drugs affected are antiretrovirals, benzodiazepines, hormonal
contraception, immunosuppressants and others like
methadone, digoxin, omeoprazol, etc.
St John's wort may also contribute to serotonin syndrome in
combination with other drugs which may elevate 5-HT levels in
the central nervous system.These drugs are antidepressants
(MAOIs, SSRIs, etc), opioids (tromadol, etc), CNS stimulants,
ilicit drugs (cocaine, LSD) and others like buspirona and lithium.
Other medical uses
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The effects of St John's wort on morphine withdrawal syndrome and
comparison with clonidine have been investigated in morphine-dependent rats.
Adult male Wistar rats were subjects. The frequencies of withdrawal behavioral
signs (rearing, teeth chattering and jumping) induced by naloxone challenge
were demonstrated in morphine dependent rats receiving Hypericum
perforatum extract (HPE), saline or clonidine. The withdrawal behavioral
manifestations in rats were inhibited significantly by chronic co-administration of
Hypericum perforatum extract or clonidine with morphine. This study showed
that clonidine was more effective than HPE at a dose of 0.4 mL/200 g and there
was no significant statistical difference between the mean frequency of
withdrawal signs of HPE at a dose of 0.8 mL/200 g compared with clonidine
(0.2 mg/kg i.p.) but at a dose of 1.2 mL/200 g of HPE was significantly stronger
than clonidine in attenuation of the morphine withdrawal syndrome.The findings
suggest that HPE is capable of reducing the symptoms of opiate withdrawal
and its effectiveness may be equivalent to clonidine in reducing the opiate
withdrawal syndrome and may have human therapeutic potential.
Other medical uses II
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Extract of the common plant Hypericum perforatum L. has been used
successfully for the treatment of mild to moderate depression since ancient
times and has recently been studied clinically. Depression and alcoholism have
some neurochemical similarities, such as low brain serotonin activities. Thus,
we hypothesized that SJW extract, which contains 0.22% hypericin and 4.05%
hyperforin, also may be effective in suppressing alcohol intake. To test this
hypothesis, the effects of SJW extract on voluntary alcohol intake were studied
in two different genetic animal models of human alcoholism: fawn-hooded (FH)
and high-alcohol drinking (HAD) rats. FH and HAD rats received a single oral
administration (5 ml/kg) of either vehicle or one of the five doses (100, 200,
400, 600, and 800 mg/kg) of SJW extract. The oral administration of SJW
extract significantly (P < 0.0001) reduced alcohol intake in both FH and HAD
rats. In a third study, FH rats did not develop tolerance to the suppressant
effects of SJW on alcohol intake and preference following oral administration of
(400 mg/kg) of the extract for 15 consecutive days. These promising findings
suggest that SJW extract should be evaluated clinically as a potential
therapeutic agent in the treatment of alcoholism.
Other medical uses III
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In recent years, interest in the hepatoprotective plants and plant
based chemicals is increasing. In Turkish folk medicine,
Hypericum perforatum L. has been used for various purposes
including liver protection. The hepatoprotective effect of H.
perforatum was investigated in vivo by cannulating the rat bile
duct for choleretic activity and by barbiturate sleeping time
following CCI4-induced hepatic injury. The increase in the bile
secretion following intraduodenal injection of H. perforatum
extract, and the appearance of its constituents in the bile were
observed by its colour change and this observation was
confirmed by thin layer chromatographic analysis suggesting
the excretion of hypericin into the bile as well. It was observed
that the extract shortens the barbiturate sleeping time of CCI4treated mice suggesting hepatoprotection.
Other medical uses IV
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Hypericin has been shown to have antibacterial and antiviral properties.
Hypericin currently is being investigated as a treatment for several bacterial
diseases, including tuberculosis, and for several viral diseases, including the
HIV and herpes simplex viruses.
The antibacterial activity of an ethanolic extract of Hypericum perforatum L. was
investigated against 8 Gram-negative bacteria (Pseudomonas fluorescens,
Pseudomonas phaseolicola, Pseudomonas glycinea, Erwinia carotovora,
Enterobacter cloacae, Klebsiella pneumoniae, Agrobacterium tumefaciens,
Azotobacter chrococcum) and 2 Gram-positive bacteria (Bacillus mycoides,
Bacillus subtilis) by the disc-diffusion and broth tube dilution methods. Ethanol
was used for extraction of the plant. The species Pseudomonas glycinea and
Azotobacter chrococcum showed extreme sensitivity to the extract of H.
perforatum, while no effect was observed on bacteria Klebsiella pneumoniae.
Minimum inhibitory concentration (MIC) of the ethanolic extract varied between
1.25 and 3.5 mg/ml. The antifungal activity of the H. perforatum extract at
concentrations of 5-45 mg/ml was determined by the method of spore counting;
a concentration of 45 mg/ml showed the greatest fungistatic activity. In the case
of inoculation of 1 x 102 spores of fungi, the number of spores was decreased:
with Fusarium oxysporum, only 5 spores were identified, and with Penicillium
canescens, 15 spores.
Other medical uses V
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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 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.
Other medical uses VI
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St. John's wort (Hypericum perforatum) is a tradional folk remedy that is used for
the topical treatment of superficial wounds, scars and burns. A characteristic
metabolite of St. John's wort is the photodynamic active plant pigment hypericin.
It is known that hypericin may cause a severe photodermatitis called hypericism
when higher amounts of St. John's wort are ingested orally. To date, no reports
on the photosensitizing capacity of topical application of St. John's wort are
available. Here, we investigated the effects of Hypericum oil (hypericin 110
μg/mL) and Hypericum ointment (hypericin 30 μg/mL) on skin sensitivity to solar
simulated radiation. Sixteen volunteers of the skin types II and III were tested on
their volar forearms with solar simulated radiation for photosensitizing effects of
Hypericum oil (n=8) and Hypericum ointment (n=8). The minimal erythema dose
(MED) was determined by visual assessment, and skin erythema was evaluated
photometrically. With the visual erythema score, no change of the MED could be
detected after application of either Hypericum oil or Hypericum ointment
(P>0.05). With the more sensitive photometric measurement, an increase of the
erythema-index after treatment with the Hypericum oil could be detected
(P≤0.01). The results do not provide evidence for a severe phototoxic potential of
Hypericum oil and Hypericum ointment, detectable by the clinically relevant
visual erythema score. However, the trend towards increased photosensitivity
detected with the more sensitive photometric measurement could become
relevant in fair-skinned individuals, in diseased skin or after extended solar
irradiation.
Bibliography
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V.Schluz,R.Hänsel,V.E.Tyler. (2001). Rational
Phytotherapy: A Physician´s Guide to Herbal
Medicine. Germany: Springer-Verlag.
http://www.ncbi.nlm.nih.gov/pubmed
http://www.hypericum.com/
http://nccam.nih.gov/health/stjohnswort/
http://cat.inist.fr
http://www.drugs.com/npc/st-john-s-wort.html
http://journals.tubitak.gov.tr/biology
http://wikipedia.en