Hyperforin

Life Sci. 1998;63(6):499-510.

Hyperforin as a possible antidepressant component of hypericum extracts.[Pubmed: 9718074 ]

METHODS AND RESULTS:
We demonstrate that the phloroglucinol derivative Hyperforin is not only the major lipophilic chemical constituent of the medicinal plant Hypericum perforatum (St. John's wort) but also a potent uptake inhibitor of serotonin (5-HT), dopamine (DA), noradrenaline (NA), GABA and L-Glutamate with IC50 values of about 0.05-0.10 microg/ml (5-HT, NA, DA, GABA) and about 0.5 microg/ml (L-glutamate) in synaptosomal preparations. Furthermore, potencies of two different hypericum extracts in two conventional pharmacological paradigms useful for the detection of antidepressants (behavioral despair, learned helplessness), closely correlate with their Hyperforin contents. In addition, most till now known neuropharmacological properties of the clinically used hypericum extracts can also be demonstrated with pure Hyperforin.
CONCLUSIONS:
It appears, therefore, that this non-nitrogenous constituent is a possible major active principle responsible for the observed clinical efficacies of the extract as an antidepressant and that it could also be a starting point for drug discovery projects engaged in the search of psychoactive drugs with novel mode of action.

Biochem Pharmacol. 2002 Dec 15;64(12):1767-75.

Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenase.[Pubmed: 12445866 ]

The acylphloroglucinol derivative Hyperforin is the major lipophilic constituent in the herb Hypericum perforatum (St. John's wort). The aim of the present study was to investigate if Hyperforin as well as extracts of H. perforatum can suppresses the activities of 5-lipoxygenase (5-LO) and cyclooxygenases (COX), key enzymes in the formation of proinflammatory eicosanoids from arachidonic acid (AA).
METHODS AND RESULTS:
In freshly isolated human polymorphonuclear leukocytes stimulated with Ca(2+) ionophore A23187, Hyperforin inhibited 5-LO product formation with IC(50) values of about 1-2 microM, in the absence or presence of exogenous AA (20 microM), respectively, being almost equipotent to the well-documented 5-LO inhibitor zileuton (IC(50) = 0.5-1 microM). Experiments with purified human 5-LO demonstrate that Hyperforin is a direct 5-LO inhibitor (IC(50) approximately 90 nM), acting in an uncompetitive fashion. In thrombin- or ionophore-stimulated human platelets, Hyperforin suppressed COX-1 product (12(S)-hydroxyheptadecatrienoic acid) formation with an IC(50) of 0.3 and 3 microM, respectively, being about 3- to 18-fold more potent than aspirin. At similar concentrations, Hyperforin suppressed COX-1 activity in platelets in presence of exogenous AA (20 microM) as well as in cell-free systems. Hyperforin could not interfere with COX-2 product formation and did not significantly inhibit 12- or 15-LO in platelets or leukocytes, respectively.
CONCLUSIONS:
We conclude that Hyperforin acts as a dual inhibitor of 5-LO and COX-1 in intact cells as well as on the catalytic activity of the crude enzymes, suggesting therapeutic potential in inflammatory and allergic diseases connected to eicosanoids.

Planta Med. 2005 Nov;71(11):999-1004.

Hyperforin acts as an angiogenesis inhibitor.[Pubmed: 16320199]

Hyperforin is a plant compound from Hypericum perforatum that inhibits tumor cell proliferation in vitro by induction of apoptosis. Here, we report that Hyperforin also acts as an angiogenesis inhibitor in vitro and in vivo.
METHODS AND RESULTS:
In vitro, Hyperforin blocked microvessel formation of human dermal microvascular endothelial cells (HDMEC) on a complex extracellular matrix. Furthermore, Hyperforin reduced proliferation of HDMEC in a dose-dependent manner, without displaying toxic effects or inducing apoptosis of the cells. To evaluate the antiangiogenic activity of Hyperforin in vivo, Wistar rats were subcutaneously injected with MT-450 mammary carcinoma cells and were treated with peritumoral injections of Hyperforin or solvent. Hyperforin significantly inhibited tumor growth, induced apoptosis of tumor cells and reduced tumor vascularization, as shown by in situ staining of CD31-positive microvessels in the tumor stroma.
CONCLUSIONS:
These data suggest that, in addition to the induction of tumor cell apoptosis, Hyperforin can also suppress angiogenesis by a direct, non-toxic effect on endothelial cells.