INHIBITION OF ARACHIDONATE RELEASE FROM RAT PERITONEAL MACROPHAGE BY BIFLAVONOIDS

Biflavonoid is one of unique classes of naturally-occurring bioflavono id. Previously, certain biflavonoids were found to possess the inhibit ory effects on phospholipase A(2) activity and lymphocytes proliferati on' suggesting their anti-inflammatory/immunoregulatory potential. In this study, effects of several biflavonoids on arachidonic acid releas e from rat peritoneal macrophages were investigated, because arachidon ic acid released from the activated macrophages is one of the indices of inflammatory conditions. When resident peritoneal macrophages label ed with [H-3]arachidonic acid were activated by phorbol 12-myristate 1 3-acetate (PMA) or calcium ionophore, A23187, radioactivity released i n the medium was increased approximately 4.1 similar to 7.3 fold after 120 min incubation compared to the spontaneous release in the control incubation. In this condition, biflavonoids (10 uM) such as ochnaflav one, ginkgetin and isoginkgetin, showed inhibition of arachidonate rel ease from macrophages activated by PMA (32.5 similar to 40.0% inhibiti on) or A23187 (21.7 similar to 41.7% inhibition). Amentoflavone showed protection only against PMA-induced arachidonate release, while apige nin, a monomer of these biflavonoids, did not show the significant inh ibition up to 10 uM. Staurosporin (1 uM), a protein kinase C inhibitor , showed an inhibitory effect only against PMA-induced arachidonate re lease (96.8% inhibition). Inhibition of arachidonate release from the activated macrophages may contribute to an anti-inflammatory potential of biflavonoids in vivo.