Download Hyperforin as a natural antidepressant: an overview

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Deepali Gharge et al. / Journal of Pharmacy Research 2009, 2(9),1373-1375
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Hyperforin as a natural antidepressant: an overview
Deepali Gharge*, Todkar Pavan, Bavaskar Sunil, Pandurang Dhabale.
*Department of Pharmaceutical Chemistry, Govt. College Of Pharmacy, Saidapur (Vidyanagar), Karad, TalKarad, Dist- Satara.(M.S.), Pin- 415 124
Received on: 16-05-2009; Accepted on 22-07-2009
ABSTRACT
Hyperforin is a structurally novel anti-depressant isolated from Hypericum perforatum commonly known as St.John’s wort. Hyperforin
belongs to group of compound known as acylphloroglucinols. The peculiarity of Hyperforin is that it is chemically unrelated to synthetic
antidepressants. Hyperforin is photo and oxygen labile compound that is highly unstable and difficult to isolate in pure form. Initially,
Hypericin, a napthodianthrone compound was considered to be the anti depressant principle of the herb, but now it is better known as marker
compound in Hypericum perforatum extract and is used as identification standard in Hypericum samples. The standardization of Hypericum
perforatum is based on presence of both Hyperforin and Hypericin.
Keywords: Anti-depressant, Hyperforin, St.John’s wort, Hypericin.
INTRODUCTION
Hyperforin exhibits significant antidepressant activity.1 Biochemical
research demonstrates that hyperforin - like many prescription antidepressants - inhibits the reuptake of the neurotransmitters norepinephrine, serotonin, and dopamine.2 All three of these compounds
are naturally found in the brain and regulate mood and emotion. They
are called “neurotransmitters” because they are chemical messengers that transmit information between nerve cells. An imbalance of
serotonin, norepinephrine, and/or dopamine can cause depression.
By acting as a “reuptake inhibitor”, hyperforin increases the levels of
these neurotransmitters in the brain, which can improve mood and
restore emotional balance.3, 4 Hyperforin also inhibits the reuptake of
GABA, a neurotransmitter that increases relaxation and reduces anxiety.
Hyperforin is not a drug, but a natural compound extracted from the
St. John’s wort (Hypericum perforatum) plant. Only in the past few
years have researchers discovered that hyperforin is the primary compound responsible for the antidepressant effect of St. John’s Wort.5
The ability of any St. John’s wort extract to relieve depression depends
mainly
on
its
hyperforin
content.
In other words, only St. John’s wort extracts with significant amounts
of hyperforin are effective. This fact was confirmed by a clinical trial,
involving 147 patients with depression, which compared placebo to
two different St. John’s wort extracts with varying amounts of
hyperforin. One extract contained only 0.5% hyperforin, the concentration found in most brands sold in the United States. The other
extract was standardized to provide 5% hyperforin, the clinicallyproven potency found in AMORYN and pharmaceutical-grade European St. John’s wort. (Aside from hyperforin content, the two extracts
were identical. Both extracts were standardized to contain 0.3% hypericin, the compound previously thought to be the active constituent in SJW.) The 5% extract was found to effectively relieve depression, but the 0.5% was ineffective and performed no better than placebo.6 This study demonstrates the importance of choosing a St.
John’s Wort extract that, like AMORYN’s, is standardized to contain a
high concentration of hyperforin.
An extensive body of research, consisting of over 30 controlled clinical trials, proves the effectiveness of hyperforin-rich St. John’s wort
extract for relieving depression.2,7,8,9,10 Because most studies used
*Corresponding author.
extracts containing at least 3% hyperforin, this research does not
Miss. Deepali S. Gharge, C/O Prof. P. N. Dhabale, Head of Department of apply to SJW extracts without a standardized quantity of hyperforin
Pharmaceutical Chemistry, Govt. College Of Pharmacy, Saidapur
(such as those commonly sold “over-the-counter” in the United
(Vidyanagar), Karad, Tal- Karad, Dist- Satara.(M.S.), Pin- 415 124.
States). In fact, a recent study found that hyperforin, in high daily
Tel.: + 91doses, is superior to the prescription drug paroxetine as a treatment
Telefax: +91for even severe depression.11
E-mail: [email protected]
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Deepali Gharge et al. / Journal of Pharmacy Research 2009, 2(9),1373-1375
Furthermore, clinical research suggests that adverse side effects occur less frequently with hyperforin than prescription antidepressants.7,9 For instance, although hyperforin was shown to relieve severe depression at least as well as Paxil®, patients taking hyperforin
reported 42% fewer side effects.11 And hyperforin rarely causes weight
gain or sexual dysfunction, side effects common with popular prescription drugs.
ACTIVE PRINCIPLES IN ST. JOHN’S WORT
The quantity and quality of active principles in Hypericin vary according to geographical locale, climate, time of day and time of year.
St. John’s wort contain dianthrone derivatives, mainly in the form of
hypericin and pseudo-hypericin 12 as well as flavonoids.13 Small
amounts of coumarins14, phenolic carboxylic compounds 15, phloroglucinol derivatives 16, monoterpenes, sesquiterpenes 17, n-alkanes 18,
n-alkanols 19, carotenoids and beta-sitosterol20 are present. The roots
contain xanthones.21
STABILITY
Hyperforin is unstable in the presence of light and oxygen.22
PHARMACOLOGY
Hyperforin is a prenylated phloroglucinol believed to be the main
active constituent responsible for the antidepressant effects of extracts of St John’s wort.23 Hyperforin has been shown to inhibit the
uptake of the neurotransmitters serotonin, dopamine, noradrenaline,
GABA and glutamate.24 It was identified as a specific activator of the
ion channel TRPC6 which is involved in neuronal axonal sprouting.
The activation of TRPC6 causes entry of sodium and calcium ions in
neuronal cells which can explain the inhibition of neurotransmitter
uptake.25 Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to the Pregnane X Receptor (PXR).26
MECHANISM OFACTION
From a number of in vivo, in vitro and clinical studies it has been
shown that that hyperforin not only inhibits the neuronal uptake of
serotonin, norepinephrine and dopamine, but it also inhibits amino
butyric acid (GABA) and L-glutamate uptake. Recently it has been
proposed that there occur a physiochemical interaction of Hyperforin
with specific membrane structures, which contribute to anti depressant activity. 27, 28
ANTIBIOTIC PROPERTIES
Hyperforin’s antibiotic properties were described before its antidepressive effects were known. It is active against methicillin-resistant
strains of Staphylococcus aureus (MRSA) with a minimal inhibitory
concentration (MIC) value of 1.0 µg/ml 29, as well as other gram-positive bacteria.30
AS EJACULATORY CONTROL
Hyperforin and other serotonin agonists significantly reduces the
pelvic floor contractions elicited by 8-OH-DPAT.31 Thus, pharmacological modulation of the ejaculatory threshold using serotonin
reuptake inhibitors and hyperforin may offer patients an option of
achieving improved ejaculatory control.
PHARMACOKINETICS
After administration of a 400mg tablet of St. John’s wort extract containing 14.8mg Hyperforin, a maximum plasma level of approximately
150ng/mL (280nM) hyperforin was reached after 3.5 hours. The oral
bioavailability of Hyperforin in doses up to 30mg (i.e. 600mg St. John’s
wort extract) was high. The half-life of Hyperforin was 9 hours and the
mean residence time 12 hours. No accumulation of Hyperforin occurred with repeated dosing. Estimated steady state plasma concentrations with 3x300mg extract per day were approximately 100ng/mL
or 180nM. These data show that the oral bioavailability of Hyperforin
is high and that steady-state plasma concentrations can easily be
achieved and maintained with a three times daily dosing schedule.
Nothing appears to be known about the metabolism of Hyperforin as
yet. 32, 33
SIDE EFFECTSAND RISKS
The most common side effects of St. John’s wort include dry mouth,
dizziness, diarrhea, nausea, increased sensitivity to sunlight, and fatigue. 34
Research has shown that taking St. John’s wort can limit the effectiveness of some prescription medicines, including:
• Antidepressant medicines 35
• Birth control pills 36
• Cyclosporine, a medicine that helps prevent the body from
rejecting transplanted organs37
• Digoxin, a medicine used to strengthen heart muscle contractions 38
• Indinavir and other medicines used to control HIV infection
39
•
•
Irinotecan and other anticancer medicines 40
Warfarin and related medicines used to thin the blood (known
as anticoagulants)41
When combined with certain antidepressants, St. John’s wort also
may increase side effects such as nausea, anxiety, headache, and
confusion.
CONCLUSION:
Now a days herbal drugs are too in demand and interaction of herbal
medicine with synthetic drugs are like a particular area of interest for
research. St. John’s wort an herbal drug also known as hyperforin,
basically hyperforin is not a drug it is isolated from the flowering tops
of the perennial plane hypericum perforatum which exhibits significant antidepressant activity by inhibiting the reuptake of the neurotransmitters norepineprine, serotonin, and dopamine. All three of
these compounds are naturally found in the brain and regulate mood
and emotion. They are called “neurotransmitters” because they are
chemical messengers that transmit information between nerve cells.
An imbalance of serotonin, norepinephrine, and/or dopamine can
cause depression. By acting as a “reuptake inhibitor”, hyperforin
increases the levels of these neurotransmitters in the brain, which can
improve mood and restore emotional balance.
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Source of support: Nil, Conflict of interest: None Declared
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