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Research Area
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Description
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Cancer |
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Biological Activity
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Description
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Ginkgolide B (BN 52021) is a PAFR antagonist with IC50 of 3.6 μM. |
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Targets
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PAFR |
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IC50 |
3.6 μM [1] |
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In Vitro
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Ginkgolide B potently inhibits a platelet-activating factor (PAF) receptor. [1] 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. [2] Ginkgolide B induces cyst cell differentiation and alteres the Ras/MAPK signaling pathway. [3] 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. [4] |
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In Vivo
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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.[3] Preischemic application of Ginkgolide B (50 mg/kg p.o.) significantly reduces neuronal damage.[5] 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. [6] 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. [7] Ginkgolide B inhibits the maturation of ischemic injury. [8] 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. [9] 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.[10] |
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Clinical Trials
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Features
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Protocol
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Animal Study
[10]
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| Animal Models |
Eight-week-old male ApoE?/? mice |
| Formulation |
PBS |
| Doses |
0.6 mg/day |
| Administration |
Intragastric administration |
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References |
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[1] Lamant V, et al. BiochemPharmacol, 1987, 36(17), 2749-2752.
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[2] Lenoir M, et al. BiochemPharmacol, 2002, 63(7), 1241-1249.
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[3] Zhou H, et al. Am J Physiol Renal Physiol, 2012, 302(10), F1234-F1242.
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[4] Tang Y, et al. Eur Cell Mater, 2011, 21, 459-469.
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[5] OberpichlerH, et al. J Cereb Blood Flow Metab, 1990, 10(1), 133-135.
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[6] Ahlemeyer B, et al. Pharmacopsychiatry, 2003, Suppl 1, S8-S14.
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[7] Desquand S, et al. Eur J Pharmacol, 1986, 127(1-2), 83-95.
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[8] Birkle DL,et al. J Neurochem, 1988, 51(6), 1900-1905.
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[9] Gu JH, et al. Eur J Pharm Sci, 2012, 47(4), 652-660.
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[10] Liu X,et al. PLoS One, 2012, 7(5), e36237.
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