IMMUNOSUPPRESSIVE EFFECTS OF HYPERICIN ON STIMULATED HUMAN-LEUKOCYTES- INHIBITION OF THE ARACHIDONIC-ACID RELEASE, LEUKOTRIENE B-4 AND INTERLEUKIN-1-ALPHA PRODUCTION, AND ACTIVATION OF NITRIC-OXIDE FORMATION
Ag. Panossian et al., IMMUNOSUPPRESSIVE EFFECTS OF HYPERICIN ON STIMULATED HUMAN-LEUKOCYTES- INHIBITION OF THE ARACHIDONIC-ACID RELEASE, LEUKOTRIENE B-4 AND INTERLEUKIN-1-ALPHA PRODUCTION, AND ACTIVATION OF NITRIC-OXIDE FORMATION, Phytomedicine, 3(1), 1996, pp. 19-28
The present study describes the influence of hypericin of Hypericum pe
rforatam on TPA- and LPS-induced arachidonic acid (AA) metabolism, as
well as interleukin 1 alpha and nitric oxide (NO) production in human
immunocompetent cells. The results show that hypericin inhibits the re
lease of arachidonic acid (AA) from membrane phospholipids in calcium
ionphore A23187-TPA stimulated human granulocytes in a dose-dependent
manner (IC50, 4 mu M), but that calcium ionophore is not the only indu
cer. An inhibitory effect could be observed at concentrations of < 0.4
mu M and in the presence of low concentrations of TPA (0.16 - 0.32 mu
M). 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
-1 alpha 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 alpha or intermed
iates of the cycloxygenase pathway. The results as a whole let us assu
me that one important mechanism for the antiviral, antiinflammatory an
d antitumoral effects of hypericin and Hypericum extracts is the inhib
ition of the PKC-mediated signalling pathway which in turn influences
the AA metabolism, and the interleukin-1 alpha production resulting in
an immunosuppressive effect on the host immune system.