Ginkgetin, a biflavone from Ginko biloba leaves, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells

Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A₂ inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase-2 (COX-2) in vitro effect. Ginkgetin inhibits COX-2 dependent phases of prostaglandin D₂ (PGD₂) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC₅₀ values of 0.75 μM. Western blotting probed with specific anti-COX-2 antibodies showed that the decrease in quantity of the PGD ₂ product was accompanied by a decrease in the COX-2 protein level. In addition, this compound consistently inhibited the production of leukotriene C₄ (LTC₄) in a dose dependent manner, with an IC ₅₀ value of 0.33 μM. These results demonstrate that ginkgetin has a dual cyclooxygenase-2/5-lipoxygenase inhibitory activity. Furthermore, this compound also inhibited degranulation reaction in a dose dependent manner, with an IC₅₀ value of 6.52 μM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.