Flavonoids: potent inhibitors of arachidonate 5-lipoxygenase

Various flavonoids were found to be relatively selective inhibitors of arachidonate 5-lipoxygenase which initiates the biosynthesis of leukotrienes with the activity of slow reacting substance of anaphylaxis. Cirsiliol (3',4',5-trihydroxy-6,7-dimethoxyflavone) was most potent, and the enzyme partially purified from rat basophilic leukemia cells was inhibited by 97% at a concentration of 10 microM (IC50, about 0.1 microM). 12-Lipoxygenases from bovine platelets and porcine leukocytes were also inhibited but at higher concentrations (IC50, about 1 microM), and fatty acid cyclooxygenase purified from bovine vesicular gland was scarcely affected. The compound at 10 microM suppressed by 99% the immunological release of slow reacting substance of anaphylaxis from passively sensitized guinea pig lung (IC50, about 0.4 microM).