Possible involvement of protein kinase C inhibition in the reduction of phorbol ester-induced neutrophil aggregation by magnolol in the rat

The influence of the plant product magnolol on neutrophil aggregation has b een investigated in the rat. Magnolol inhibited phorbol 12-myristate 13-acetate (PMA)-activated fat neut rophil aggregation in a concentration-dependent manner with an IC50 (concen tration resulting in 50% inhibition) of 24.2 +/- 1.7 mu M. Magnolol suppres sed the enzyme activity of neutrophil cytosolic and rat brain protein kinas e C (PKC) over the same range of concentrations at which it inhibited the a ggregation. Magnolol did not affect PMA-induced cytosolic PKC-a and -delta membrane translocation or trypsin-treated rat-brain PKC activity, but atten uated [H-3]phorbol 12,13-dibutyrate binding to neutrophil cytosolic PKC. These results suggest that the inhibition of PMA-induced rat neutrophil agg regation by magnolol is probably attributable, at least in part, to the dir ect suppression of PKC activity through blockade of the regulatory region o f PKC.