Hyperforin
Encyclopedia
Hyperforin is a phytochemical
produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort
).
. Other Hypericum species contain low amounts of hyperforin.
phloroglucinol
derivative. An enantioselective total synthesis of hyperforin was reported in 2010.
Hyperforin is unstable in the presence of light and oxygen
.
and anxiolytic
properties of the extracts of St. John's wort. It acts as a reuptake inhibitor
of monoamines, including serotonin
, norepinephrine
, dopamine
, and of GABA
and glutamate, with IC50
values of 0.05-0.10 mcg/ml for all compounds, with the exception of glutamate, which is in the 0.5 mcg/ml range. It appears to exert these effects by activating the transient receptor potential
ion channel
TRPC6
. Activation of TRPC6 induces the entry of sodium
and calcium
into the cell which causes inhibition of monoamine reuptake.
Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzyme
s CYP3A4
and CYP2C9
by binding to and activating the pregnane X receptor (PXR).
Some pharmacokinetic data on hyperforin is available for an extract containing 5% hyperforin. Maximal plasma levels (Cmax
) in human volunteers were reached 3.5h after administration of an extract containing 14.8 mg hyperforin. Biological half-life
(t½) and mean residence time were 9h and 12h respectively with an estimated steady state plasma concentration of 100 ng/ml (approx. 180 nM/L) for 3 doses/d. Linear plasma concentrations were observed within a normal dosage range and no accumulation occurred.
properties and is active against methicillin
-resistant strains of Staphylococcus aureus
(MRSA) with a minimal inhibitory concentration (MIC) value of 1.0 μg/ml, as well as against other gram-positive bacteria.
Phytochemical
Phytochemicals are biologically active chemical compounds that occur naturally in plants . Phytochemicals are the molecules responsible for the color and organoleptic properties . For example, the deep purple color of blueberries and the smell of garlic...
produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort
St John's wort
St John's wort is the plant species Hypericum perforatum, and is also known as Tipton's Weed, Chase-devil, or Klamath weed....
).
Occurrence
Hyperforin has only been found in significant amounts in Hypericum perforatum (St John's wort), where it accumulates in oil glands, pistils, and fruits, probably as a plant defense against herbivoryPlant defense against herbivory
Plant defense against herbivory or host-plant resistance describes a range of adaptations evolved by plants which improve their survival and reproduction by reducing the impact of herbivores. Plants use several strategies to defend against damage caused by herbivores...
. Other Hypericum species contain low amounts of hyperforin.
Chemistry
The structure of hyperforin was elucidated by a research group from the Shemyakin Institute of Bio-organic Chemistry (USSR Academy of Sciences in Moscow) and published in 1975. Hyperforin is a prenylatedPrenylation
Prenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...
phloroglucinol
Phloroglucinol
Phloroglucinol is a benzenetriol. It is an organic compound that is used in the synthesis of pharmaceuticals and explosives. This molecule exists in two forms, or tautomers, 1,3,5-trihydroxybenzene, which has phenol-like, and 1,3,5-cyclohexanetrione , which has ketone-like character. These two...
derivative. An enantioselective total synthesis of hyperforin was reported in 2010.
Hyperforin is unstable in the presence of light and oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
.
Pharmacology
Hyperforin is believed to be the primary active constituent responsible for the antidepressantAntidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
and anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
properties of the extracts of St. John's wort. It acts as a reuptake inhibitor
Reuptake inhibitor
A reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...
of monoamines, including serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, and of GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
and glutamate, with IC50
IC50
The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance is needed to inhibit a given biological process by half...
values of 0.05-0.10 mcg/ml for all compounds, with the exception of glutamate, which is in the 0.5 mcg/ml range. It appears to exert these effects by activating the transient receptor potential
Transient receptor potential
Transient receptor potential channels are a group of ion channels located mostly on the plasma membrane of numerous human and animal cell types. There are about 28 TRP channels that share some structural similarity to each other...
ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
TRPC6
TRPC6
Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential ion channel...
. Activation of TRPC6 induces the entry of sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
and calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
into the cell which causes inhibition of monoamine reuptake.
Hyperforin is also thought to be responsible for the induction of the cytochrome P450 enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
and CYP2C9
CYP2C9
Cytochrome P450 2C9 is a protein that in humans is encoded by the CYP2C9 gene.- Function :CYP2C9 is an important cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes...
by binding to and activating the pregnane X receptor (PXR).
Some pharmacokinetic data on hyperforin is available for an extract containing 5% hyperforin. Maximal plasma levels (Cmax
Cmax
cmax may refer to:* Customatix, a footwear company* C Max, a maximum security prison in South Africa* Ford C-MAX, a model of car* Cmax - the maximum concentration of a drug in the body after dosing....
) in human volunteers were reached 3.5h after administration of an extract containing 14.8 mg hyperforin. Biological half-life
Biological half-life
The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
(t½) and mean residence time were 9h and 12h respectively with an estimated steady state plasma concentration of 100 ng/ml (approx. 180 nM/L) for 3 doses/d. Linear plasma concentrations were observed within a normal dosage range and no accumulation occurred.
Antibiotic
Hyperforin has antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
properties and is active against methicillin
Methicillin
Meticillin or methicillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It should not be confused with the antibiotic metacycline.-History:Methicillin was developed by Beecham in 1959...
-resistant strains of Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
(MRSA) with a minimal inhibitory concentration (MIC) value of 1.0 μg/ml, as well as against other gram-positive bacteria.