Ginkgolide B is a terpene lactone extracted from Ginkgo biloba leaves and is a specific antagonist of platelet activating factor (PAF), with an IC50 of 3.6μM[1]. Platelet activating factor (PAF) is a phospholipid inflammatory mediator that rapidly activates platelets, white blood cells and endothelial cells by binding to PAFR, amplifying inflammatory and thrombotic responses[2]. Ginkgolide B has antioxidant, anti-inflammatory, anti-tumor, and anti-apoptotic activities and is commonly used for research on ischemia/reperfusion injury, neuroinflammation, and tumors[3-5].
In vitro, treatment of Human umbilical vein endothelial cells (HUVECs) with Ginkgolide B (30–300μM; 24h) dose-dependently increased PXR nuclear translocation, upregulated CYP3A4 and MDR1 expression, attenuated doxorubicin- or staurosporine-induced apoptosis, and suppressed TNF-α-induced THP-1 cell adhesion and expression of VCAM-1 and E-selectin[6].
In vivo, in rat model of cerebral ischemia/reperfusion injury, Ginkgolide B(20mg/kg; i.p.; 14days) significantly reduce the volume of cerebral infarction and the neurological deficit score, increased the proportion of nestin-, neuron-specific enolase- and glial fibrillary acid protein-positive cells, increased the mRNA expression of brain-derived neurotrophic factor(BDNF) and epidermal growth factor(EGF), and increased the expression levels of BDNF and suppressor of cytokine signaling 2(SOCS2) in the ischemic penumbra[7]. In pentobarbitone or ethyl carbamate-anaesthetized guinea-pigs, Ginkgolide B (1mg/kg; i.v.; 1h) inhibited bronchoconstriction, the hematocrit increase and the accompanying thrombopenia and leukopenia induced by PAF-acether[8].
References:
[1] Lamant V, Mauco G, Braquet P, Chap H, Douste-Blazy L. Inhibition of the metabolism of platelet activating factor (PAF-acether) by three specific antagonists from Ginkgo biloba. Biochem Pharmacol. 1987;36(17):2749-2752.
[2] Venable ME, Zimmerman GA, McIntyre TM, Prescott SM. Platelet-activating factor: a phospholipid autacoid with diverse actions. J Lipid Res. 1993;34(5):691-702.
[3] Koltai M, Tosaki A, Hosford D, Braquet P. Ginkgolide B protects isolated hearts against arrhythmias induced by ischemia but not reperfusion. Eur J Pharmacol. 1989;164(2):293-302.
[4] Lee CW, Lin HC, Wang BY, et al. Ginkgolide B monotherapy reverses osteoporosis by regulating oxidative stress-mediated bone homeostasis. Free Radic Biol Med. 2021;168:234-246.
[5] Ahlemeyer B, Krieglstein J. Pharmacological studies supporting the therapeutic use of Ginkgo biloba extract for Alzheimer's disease. Pharmacopsychiatry. 2003;36 Suppl 1:S8-S14.
[6] Zhou T, You WT, Ma ZC, et al. Ginkgolide B protects human umbilical vein endothelial cells against xenobiotic injuries via PXR activation. Acta Pharmacol Sin. 2016;37(2):177-186.
[7] Zheng PD, Mungur R, Zhou HJ, Hassan M, Jiang SN, Zheng JS. Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury, both in vivo and in vitro. Neural Regen Res. 2018;13(7):1204-1211.
[8] Desquand S, Touvay C, Randon J, et al. Interference of BN 52021 (ginkgolide B) with the bronchopulmonary effects of PAF-acether in the guinea-pig. Eur J Pharmacol. 1986;127(1-2):83-95.
Ginkgolide B是从银杏叶中提取的一种萜内酯，是血小板活化因子（PAF）的特异性拮抗剂, IC50为3.6μM[1]。 血小板活化因子（PAF）是一种磷脂类炎症介质，通过与PAFR结合迅速激活血小板、白细胞和内皮细胞，放大炎症与血栓反应[2]。Ginkgolide B具有抗氧化、抗炎、抗肿瘤和抗凋亡活性，常用于缺血/再灌注损伤、神经炎症及肿瘤等研究[3-5]。
体外实验中，用Ginkgolide B（30–300μM；24小时）处理人脐静脉内皮细胞（HUVECs），剂量依赖性地增加PXR核转位，上调CYP3A4和MDR1的表达，减轻多柔比星或司他霉素诱导的细胞凋亡，并抑制TNF-α诱导的THP-1细胞黏附以及VCAM-1和E-选择素的表达[6]。
体内实验中，在大鼠脑缺血/再灌注损伤模型中，Ginkgolide B（20mg/kg；腹腔注射；连续14天）显著减少脑梗死体积和神经功能缺损评分，增加巢蛋白、神经特异性烯醇化酶和胶质纤维酸性蛋白阳性细胞的比例，提高脑源性神经营养因子（BDNF）和表皮生长因子（EGF）的mRNA表达水平，并增加缺血半暗带中BDNF和细胞因子信号转导抑制因子2（SOCS2）的表达水平[7]。在用戊巴比妥或乙基卡巴明麻醉的豚鼠中，Ginkgolide B（1mg/kg静脉注射；1小时）抑制了PAF-乙醚诱导的支气管收缩、血细胞比容增加以及伴随的血小板减少和白细胞减少[8]。