| In Vitro | In vitro activity: Ginkgolide B potently inhibits a platelet-activating factor (PAF) receptor. Treatment of PMN with ginkgolide B (0.5 μM -12 μM) stimulates a rapid and weak production of reactive oxygen species determined by chemiluminescence. Ginkgolide B potentiates the CL response induced by fMet-Leu-Phe and zymosan. Ginkgolide B induces cyst cell differentiation and alteres the Ras/MAPK signaling pathway. Ginkgolide B promotes the proliferation and endothelial gene expression, and markedly enhances vascular endothelial growth factor-induced migration response and the capability to incorporate into the vascular networks in EPCs. Ginkgolide B protects EPCs from H2O2-induced cell death. Ginkgolide B induces the phosphorylation of eNOS, Akt and p38, which in turn promotes cell proliferation and function. |
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| In Vivo | Ginkgolide B (2 μM) significantly inhibits MDCK cyst formation dose dependently, with up to 69% reduction. Ginkgolide B also significantly inhibits cyst enlargement in the MDCK cyst model, embryonic kidney cyst model, and PKD mouse model. Preischemic application of Ginkgolide B (50 mg/kg p.o.) significantly reduces neuronal damage. 30 minutes of pretreatment with Ginkgolide B (100 mg/kg, s. c.) reduces the infarct area in the mouse model of focal ischemia. In primary cultures of hippocampal neurons and astrocytes from neonatal rats, Ginkgolide B (1 μM) protects the neurons against damage caused by glutamate. Ginkgolide B (100 μM) reduces apoptotic damage induced by staurosporine. In pentobarbitone or ethyl carbamate-anaesthetized animals, Ginkgolide B (1 mg/kg i.v. or 10 mg/kg p.o.) inhibits bronchoconstriction, the hematocrit increase and the accompanying thrombopenia and leukopenia induced by PAF-acether (33 ng/kg–100 ng/kg). Ginkgolide B at a dose of 3 mg/kg reduces the bronchoconstriction induced by aerosolized PAF-acether. Ginkgolide B at a dose of 300 μM also inhibits the superoxide production by PAF-acether-stimulated alveolar macrophages. Ginkgolide B blocks the formation of thromboxane-triggered by PAF-acether (100 ng) injected into perfused lung.Pretreatment of parenchyma lung strips with Ginkgolide B (100 μM) partially inhibits the contraction induced by PAF-acether (0.1 μM) and suppresses the accompanying release of thromboxane. Ginkgolide B inhibits the maturation of ischemic injury. Ginkgolide B treatment reveals marked reduction in infarction volume, brain edema and neurological deficits. Ginkgolide B also inhibitsischemia/reperfusion (I/R) induced NF-κB, microglia activation and production of pro-inflammatory cytokines. Ginkgolide B reducesBax protein levels and increases Bcl-2 protein levels in the post-ischemic brains. Ginkgolide B attenuates platelet aggregation and inhibits phosphatidylinositol 3 kinase (PI3K) activation and Akt phosphorylation in thrombin- and collagen-activated platelets.Ginkgolide B decreases plasma PF4 and RANTES levels in ApoE–/– mice.Ginkgolide B diminishes P-selectin, PF4, RANTES, and CD40L expression in aortic plaque in ApoE–/– mice.Moreover, ginkgolide B suppresses macrophage and vascular cell adhesion protein 1 (VCAM-1) expression in aorta lesions in ApoE–/– mice. |
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