Zeitschrift für Phytotherapie 2008; 29 - P12
DOI: 10.1055/s-2008-1047859

Divergent effects of hyperforin on the release of arachidonic acid in human platelets and polymorphonuclear leukocytes

M Hoffmann 1, C Feisst 1, PJ Jakobsson 2, D Steinhilber 1, O Werz 3
  • 1Institute of Pharmaceutical Chemistry, University of Frankfurt, Max-von-Laue-Str. 9, 60439 Frankfurt, Germany
  • 2Center for Molecular Medicine, Karolinska Institute, 17176 Stockholm, Sweden
  • 3Pharmaceutical Institute, University of Tuebingen, Auf der Morgenstelle 8, 72076 Tuebingen, Germany

Hyperforin is a main active ingredient of St. John's wort (Hypericum perforatum). Beside its anti-depressive, anti-bacterial and anti-tumoral properties, it possesses anti-inflammatory efficacy visualized by repression of proliferation of T-lymphocytes as well as inhibition of 5-lipoxygenase and cyclooxygenase-1. Here, we report about the influence of hyperforin on the activity of cytosolic phospholipase A2 (cPLA2). cPLA2 is essential for the release of arachidonic acid (AA) from cellular membranes which is converted to eicosanoids such as prostaglandins and leukotrienes.

In PMNL challenged by ionophore A23187, hyperforin blocked the release of AA with an IC50=2µM. However, in human platelets hyperforin evoked a concentration-dependent liberation of AA which was maximal at 10µM hyperforin and was accompanied by a redistribution of cPLA2 from a soluble locale to a membraneous compartment. The effects of hyperforin in platelets as well as in PMNL were not due to interferences with the intracellular Ca2+ levels or the phosphorylation status of cPLA2.

Investigations in cell-free assays using purified human recombinant cPLA2 revealed that the effects of hyperforin on cPLA2 activity are not due to an direct activation or inhibition of cPLA2 but depend on the phospholipid composition of liposomes that contain esterified AA. We suggest that hyperforin influences cPLA2 independently of intracellular Ca2+ and phosphorylation events, apparently by affecting the interaction of cPLA2 with phospholipid membranes.