Inhibition of lysoPAF acetyltransferase activity by flavonoids

Objective and Design. Several kinds of flavonoids, widely distributed natural products of the vegetable kingdom which possess anti-inflammatory activity, were examined for inhibitory effects on the acetyl-CoA: 1-alkyl-2-lyso-sn-glycero-3-phosphocholine (lysoPAF) acetyltransferase activity. Methods: Acetyl-CoA:lysoPAF acetyltransferase activity was determined using homogenates of a rat mucosal-type mastcytoma cell line, RBL-2H3 as an enzyme source. The production of platelet-activating factor (PAF) in rat peripheral white blood cells stimulated with the calcium ionophore A23187 was studied. Results: Of the flavonoids tested, luteolin and quercetin exhibited significant inhibitory effects (IC50, 45 mu M and 80 mu M, respectively), whereas other structurally-related flavonoids failed to affect the lysoPAF acetyltransferase activity. Luteolin did not suppress the activity of choline acetyltransferase, suggesting that the inhibition observed here was specific. Luteolin also inhibited the production of PAF in rat peripheral white blood cells. Conclusions: These results indicate that luteolin could become a leading compound for developing a novel type of anti-inflammatory, anti-allergic drugs that target lysoPAF acetyltransferase.