Plant-Derived Acetophenones with Antiasthmatic and Anti-Inflammatory Properties: Inhibitory Effects on Chemotaxis, Right Angle Light Scatter and Actin Polymerization of Polymorphonuclear Granulocytes

Abstract:

P>3-Methoxy- and 2-hydroxy-3-methyl substituted 4-hydroxyacetophenones and some of the corresponding 4-O-glucosides revealed inhibitory activity on LTB₄-, fMLP- and PAF-induced chemotaxis of polymorphonuclear granulocytes (PMN). Blocking of PMN myeloperoxidase (MPO), which is required for the intracellular activation of acetophenones, caused a loss of activity. By in vitro activation of apocynin (1) with human MPO and H₂O₂ and subsequent chromatographic purification an apocynin-free fraction was obtained, which contained the major metabolite. The fraction showed strong anti-chemotactic activity, which was largely preserved despite of MPO-blockade. The influences on right angle light scatter and actin polymerization in PMN demonstrate the inhibitory effects of acetophenones on the cytoskeletal rearrangement after stimulation with fMLP. Acetosyringenin (2) was shown to reduce mastoparan-induced PMN migration. The inhibition of receptor independent motility of PMN suggests that the active metabolites of acetophenones may interfere with the post receptor signalling.

Key words:

Acetophenones - apocynin - acetosyringenin - polymorphonuclear granulocytes - chemotaxis - right angle light scatter - actin polymerization - inflammation - asthma