title: Immunosuppressive effects of hypericin on stimulated human leukocytes: inhibition of the arachidonic acid release, leukotriene B(4) and Interleukin-Iα production, and activation of nitric oxide formation.
abstract: The present study describes the influence of hypericin of Hypericum perforatum on TPA- and LPS-induced arachidonic acid (AA) metabolism, as well as interleukin 1 α and nitric oxide (NO) production in human immunocompetent cells. The results show that hypericin inhibits the release of arachidonic acid (AA) from membrane phospholipids in calcium ionphore A23187-TPA stimulated human granulocytes in a dose-dependent manner (IC(50) 4 μM), but that calcium ionophore is not the only inducer. An inhibitory effect could be observed at concentrations of < 0.4 μM and in the presence of low concentrations of TPA (0.16 - 0.32 μM). As a result of this inhibition hypericin inhibits the release of LTB(4) but not of PGE(2). Hypericin also inhibits the production of IL-1α in LPS-stimulated human monocytes and activates NO production in isolated human leukocytes. This effect is comparable to the effect of LPS and is probably not associated with the IL 1 a or intermediates of the cycloxygenase pathway. The results as a whole let us assume that one important mechanism for the antiviral, antiinflammatory and antitumoral effects of hypericin and Hypericum extracts is the inhibition of the PKC-mediated signalling pathway which in turn influences the AA metabolism, and the interleukin-1 α production resulting in an immunosuppressive effect on the host immune system.
authors.affiliation: C. Guelbenkian Laboratories of the Drug Administration and the National Academy of Science of Armenia, Yekmalian 6, 375002 Yerevan, Armenia.
authors.forename: A G
authors.initials: AG
authors.lastname: Panossian
authors.forename: E
authors.initials: E
authors.lastname: Gabrielian
authors.forename: V
authors.initials: V
authors.lastname: Manvelian
authors.forename: K
authors.initials: K
authors.lastname: Jurcic
authors.forename: H
authors.initials: H
authors.lastname: Wagner