Hyperforin has only been found in significant amounts in Hypericum perforatum (St. John's wort) with other related species such as Hypericum calycinum (Greater St. John's wort or Aaron's beard) containing lower levels of the phytochemical. It is thought to be a reuptake inhibitor. It accumulates in oil glands, pistils, and fruits, probably as a plant defense against herbivory. Other Hypericum species contain low amounts of hyperforin.
Hyperforin is a prenylatedphloroglucinol 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.
Hyperforin is unstable in the presence of light and oxygen.
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 (t1/2) and mean residence time were 9h and 12h respectively with an estimated steady state plasma concentration of 100 ng/mL (approx. 180 nM) for 3 doses/d. 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. It appears to be metabolised, at least in part, by CYP3A and CYP2B into hydroxyl metabolites.
Its action on TRPC6 may enable it to protect from ischaemic brain injury. Its action on the TRPC6 cation channel is also believed to be responsible for its BDNF-like modulation of dendritic spine morphology in hippocampal pyramidal neurons.
Hyperforin has been found to be a potent inhibitor of COX-1 and 5-LO with IC50 values of 300nM and 90nM respectively, giving it an anti-inflammatory action of approximately 3-18 times stronger than aspirin.
Procognitive effects of hyperforin have been observed in rats.In vivo evidence suggests its efficacy against Alzheimer's disease, an action it seems to share with its analogue, tetrahydrohyperforin.
Hyperforin also has anticancer effects, both in vitro and in vivo, which are likely the result of its both anti-angiogenic and pro-apoptotic effects. Several chemical analogues of hyperforin have also exhibited anticancer effects in vitro and in vivo. Hyperforin also has anticlastogenic effects. Hyperforin also inhibits SIRT1 and SIRT2 with a IC50 of 15±0.5μM and 28±0.2μM respectively.
In 2008 it was reported that men with premature ejaculation that were administered an immediate-release oral formulation reported lasting longer. Hyperforin promotes mitochondrial function and the development of oligodendrocytes.
Extracts of hypericum perforatum and the hyperforin, analogue, IDN-5491 (hyperforin-trimethoxybenzoate) possess antidepressant-like effects that are dependent on the sigma and D2 receptors.
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