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).
D000818:Animals; D001091:Arachidonate Lipoxygenases; D001792:Blood Platelets / Q000201:enzymology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D006168:Guinea Pigs; D007962:Leukocytes / Q000201:enzymology; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D013189:SRS-A / Q000378:metabolism; D013552:Swine
D047309:Flavones; D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; C039824:cirsiliol; D001091:Arachidonate Lipoxygenases