Abstract
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 0.75 microM. 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 0.33 microM. 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 6.52 microM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arachidonate 5-Lipoxygenase / metabolism
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Biflavonoids / chemistry
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Biflavonoids / isolation & purification
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Biflavonoids / pharmacology*
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Bone Marrow Cells / drug effects*
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Bone Marrow Cells / metabolism
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism
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Cyclooxygenase 2 Inhibitors / chemistry
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Dose-Response Relationship, Drug
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Flavonoids / chemistry
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Flavonoids / isolation & purification
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Flavonoids / pharmacology*
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Ginkgo biloba*
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Interleukin-10 / pharmacology
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Leukotriene C4 / antagonists & inhibitors
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Leukotriene C4 / genetics
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Leukotriene C4 / metabolism
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Lipopolysaccharides / pharmacology
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Lipoxygenase Inhibitors*
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Male
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Mast Cells / drug effects*
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Mast Cells / metabolism
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Mast Cells / pathology
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred BALB C
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Plant Leaves
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Prostaglandin D2 / antagonists & inhibitors
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Prostaglandin D2 / metabolism
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Up-Regulation
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beta-N-Acetylhexosaminidases / antagonists & inhibitors
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beta-N-Acetylhexosaminidases / metabolism
Substances
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Biflavonoids
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Cyclooxygenase 2 Inhibitors
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Flavonoids
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Lipopolysaccharides
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Lipoxygenase Inhibitors
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Membrane Proteins
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Interleukin-10
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Leukotriene C4
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ginkgetin
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Arachidonate 5-Lipoxygenase
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Cyclooxygenase 2
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PTGS2 protein, human
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beta-N-Acetylhexosaminidases
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Prostaglandin D2