Abstract
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). 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 μM, in the absence or presence of exogenous AA (20 μM), respectively, being almost equipotent to the well-documented 5-LO inhibitor zileuton ( ic 50=0.5 –1 μM). Experiments with purified human 5-LO demonstrate that hyperforin is a direct 5-LO inhibitor ( ic 50≈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 μM, 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 μM) 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. 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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.