Dose dependent reversal effects of plumbagin on metabolism of arachidonic acid in porcine polymorphonuclear leukocytes

A G Panossian; B Müller-Jakic; R Bauer; H Wagner

doi:10.1016/S0944-7113(11)80005-X

Dose dependent reversal effects of plumbagin on metabolism of arachidonic acid in porcine polymorphonuclear leukocytes

Phytomedicine. 1995 Apr;1(4):291-8. doi: 10.1016/S0944-7113(11)80005-X.

Authors

A G Panossian¹, B Müller-Jakic, R Bauer, H Wagner

Affiliation

¹ Erevan Institute of Medical Radiology, Dept. of Medicinal Chemistry and Biochemical Pharmacology, Davidashen P/Box 25, Erevan, 375078, Armenia.

PMID: 23196017
DOI: 10.1016/S0944-7113(11)80005-X

Abstract

The cytostatic immunostimulating naphthoquinone plumbagin was used as a model to explain the multiple potential of immunostimulants and their interferences with the arachidonic acid metabolism. Plumbagin was found to suppress totally the activity of lipoxygenases and the endogenous production of proinflammatory immunostimulants LTB(4), 5-HETE and 12-HETE in ionophore A-23187 stimulated porcine granulocytes at a concentration of 10(-4) M, whereas it stimulates the AA-metabolism and increases e. g. the 5-lipoxygenase products in a concentration range of 10(-6)-10(-7)M. Surprisingly this stimulating effect is interrupted at a concentration of 10(-8)-10(-9) M resulting in a strong suppression of the biosynthesis of 5-lipoxygenase products. This inhibition might be associated with an increased production of "antiinflammatory" 15-HETE which is known to inhibit 5-lipoxygenase and LTB(4) production. The effects observed for plumbagin support the close linkages of AA metabolism with the unspecific immune system, and might explain the dose dependent antiinflammatory or proinflammatory effects respectively.