|Metabolism||Hepatic and CYP3A & CYP2B|
|Elimination half-life||9-19.64 hours|
|Chemical and physical data|
|3D model (JSmol)|
|Melting point||79–80 °C (174–176 °F)|
|Solubility in water||0.66 mg/mL (20 °C)|
|(what is this?)|
Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum (St John's wort). Hyperforin is attributed to provide the main antidepressant effect of St. John's wort, although there is little clinical evidence that hyperforin and St. John's wort have any effect on depression.
Hyperforin has only been found in significant amounts in Hypericum perforatum with other related species such as Hypericum calycinum containing lower levels of the phytochemical. It accumulates in oil glands, pistils, and fruits, probably as a plant defensive compound. Other Hypericum species contain low amounts of hyperforin.
Hyperforin is a prenylated phloroglucinol derivative. 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. A total synthesis of the non-natural enantiomer of hyperforin was reported in 2010 and a total synthesis of the natural enantiomer was disclosed in 2012.
Some pharmacokinetic data on hyperforin is available for an extract containing 5% hyperforin. Maximal plasma levels (Cmax) in human volunteers were reached 3.5 hours after administration of an extract containing 14.8 mg hyperforin. Biological half-life (t1/2) and mean residence time were 9 hours and 12 hours, respectively, with an estimated steady state plasma concentration of 100 ng/mL (approx. 180 nM) for 3 doses per day. Linear plasma concentrations were observed within a normal dosage range and no accumulation occurred.
In healthy male volunteers, 612 mg dry extract of St. John's wort produced hyperforin pharmacokinetics characterised by a half life of 19.64 hours.
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Hyperforin may be a constituent responsible for the antidepressant and anxiolytic properties of the extracts of St. John's wort. In vitro, it acted as a reuptake inhibitor of monoamines, including serotonin, norepinephrine, dopamine, and of GABA and glutamate, with IC50 values of 0.05-0.10 μg/mL for all compounds, with the exception of glutamate, which is in the 0.5 μg/mL range. In other laboratory studies, hyperforin induced cytochrome P450 enzymes CYP3A4 and CYP2C9 by binding to and activating the pregnane X receptor.
|Norepinephrine||80 ± 24|
|Dopamine||102 ± 19|
|GABA||184 ± 41|
|5-HT||205 ± 45|
|Glutamate||829 ± 687|
|Binding affinity (human receptors)|
|Natural and semi-synthetic analogues of Hyperforin|
Two meta-analyses of clinical trials evaluating the efficacy of St. John's wort for treating mild-to-moderate depression indicated a response similar to selective serotonin reuptake inhibitors and with better tolerance, although the quality of the studies reviewed was limited by low numbers of subjects and short durations of treatment.
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