Effects of Caffeoylglycosides on Arachidonate Metabolism in Leukocytes

Abstract

The effects of caffeoylglycosides (forsythiaside, suspensaside, acteoside, and β-hydroxyacteoside), isolated from dried fruits of Forsythia species, on the formations of the 5-lipoxygenase products 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) and leukotriene B₄ (LTB₄), the 15-lipoxygenase product 15-hydroxy-5,8,11,13-eicosastetraenoic acid (15-HETE) and the cyclooxygenase products 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT), thromboxane B₂ and 6-keto-PGF_1α in rat peritoneal cells and human peripheral polymorphonuclear leukocytes were studied. Forsythiaside, suspensaside, acteoside, and β-hydroxyacteoside were found to inhibit selectively the formation of the 5-lipoxygenase products 5-HETE and LTB₄ in human peripheral polymorphonuclear leukocytes; their concentrations for 50% inhibition (IC₅₀) of 5-HETE formation being 1.92, 49.0, 4.85, and 40.0 µM, and their IC₅₀ values for LTB₄ formation being 1.01, 8.85, 2.93, and 8.50 µM, respectively.

Forsythiaside, suspensaside, acteoside, and β-hydroxyacteoside inhibited the formation of 5-HETE from arachidonic acid in rat peritoneal cells, their IC₅₀ values on its formation being 2.50, 7.97, 5.27, and 19.3 µM, respectively. Forsythiaside caused non-competitive inhibition of 5-HETE formation.