Ginkgetin, a Biflavone from <i>Ginko biloba</i> Leaves, Inhibits Cyclooxygenases-2 and 5-Lipoxygenase in Mouse Bone Marrow-Derived Mast Cells

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 m mM. 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 m mM. 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 m mM. Therefore, this compound might provide a basis for novel anti-inflammatory agents.

Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt–dependent matrix metalloproteinase-9 expression

“…Modern work with flavonoids, the components that affect blood circulation, was initiated by the isolation of ginkgetin, but there are only a few reports on the effects of ginkgetin and isoginkgetin on cell physiology. Ginkgetin has been shown to decrease cyclooxygenase (COX)-2 expression, and consequently, inhibits COX-2 -dependent phases of prostaglandin D2 generation and leukotriene C4 (22). Ginkgetin Figure 5.…”

Inhibition of 5-Lipoxygenase Product Synthesis by Natural Compounds of Plant Origin

“…In fact, the flavonoid quercetin 11 that suppresses 5-LO product synthesis also blocks the ERK1/2 and p38 MAPK pathway [58], [59], and plantderived tyrosine kinase inhibitors such as genistein reduced 5-LO activation in HL60 cells [47]. Moreover, agents that cause elevation of cAMP (e. g., ginkgetin 25 from Ginkgo biloba, a potent inhibitor of cellular 5-LO product synthesis [40], [60]) and thus stimulation of PKA may suppress 5-LO activity and translocation by such mechanisms.…”

“…Interestingly, 5-LO and cPLA 2 share structural (C2 domain) and regulatory properties [activated by Ca 2+ and by phosphorylation by members of the mitogen-activated protein kinase (MAPK) family] [31], [34]. Indeed, many studies revealed that natural compounds (e. g., flavonoids and other polyphenols) leading to suppression of LT formation also act as PLA 2 inhibitors preventing AA release [35], [36], [37], [38], [39], [40]. The anti-inflammatory sesterterpenoid manoalide, for instance, is an irreversible inhibitor of PLA 2 enzymes by covalently modifying lysine residues [41].…”

Therapeutic dose of Ginkgo biloba extract 761 may alter the urine excretion of Wistar rats

“…Collectively, these data suggest that GBE is comparable to acetylsalicylic acid in terms of the inhibition of TXB2 and COX-1 (Kudolo et al, 2004). Attention of the side effects of conventional AINE'S (Non-steroidal anti-inflammatory drugs) including gastrointestinal and renal toxicity (Son et al, 2005).…”

“…One of the molecules derived from Ginkgo biloba leaves, a biflavone known as Ginkgetin, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells (Son et al, 2005;Park et al, 2006). The importance of the cyclooxygenases pathways in the control of blood pressure is illustrated by the use of AINE'S in humans, which inhibit both cyclooxygenases 1 or 2 isoforms and cause Na + retention and hypertension.…”