Hyperforin

Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort).

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 herbivory. 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 prenylated phloroglucinol derivative. An enantioselective total synthesis of hyperforin was reported in 2010.

Hyperforin is unstable in the presence of light and oxygen.

Pharmacology
Hyperforin is believed to be the primary active constituent responsible for the antidepressant 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 enzymes 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.

Antibiotic
Hyperforin has antibiotic 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.