Ginkgetin, a Biflavone from Ginko biloba Leaves, Inhibits Cyclooxygenases-2 and 5-Lipoxygenase in Mouse Bone Marrow-Derived Mast Cells(Biochemistry)

Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A_2 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 D_2 (PGD_2) generation in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with IC_<50> values of 0.75μm. 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 C_4 (LTC_4) in a dose dependent manner, with an IC_<50> value of 0.33μM. 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 IC_<50> value of 6.52μM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.