Heme oxygenase 1, beneficial role in permanent ischemic stroke and in Gingko biloba (EGb 761) neuroprotection.
Heme oxygenase 1, beneficial role in permanent ischemic stroke and in Gingko biloba (EGb 761) neuroprotection.
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DOI：
10.1016/j.neuroscience.2011.02.031
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发表时间：
2011-04-28
期刊：
影响因子：
3.3
通讯作者：
Dore, S.
中科院分区：
文献类型：
--
作者：
Shah, Z. A.;Nada, S. E.;Dore, S.
银杏叶提取物是一种常用的标准化天然提取物，含有24%的银杏黄酮苷和6%的萜内酯。银杏叶提取物761在世界范围内被用于治疗许多疾病，虽然许多研究表明其具有神经保护作用，但其作用机制尚未完全阐明。我们推测，银杏内酯761及其部分生物活性成分[白果内酯(BB)、银杏内酯A(GA)、银杏内酯B(GB)和无萜烯类物质(TFM)]可能通过血红素加氧酶1(HO1)发挥神经保护作用。小鼠大脑中动脉远端永久性闭塞(PMCAO)，存活7d。与野生型(WT)小鼠相比，HO1-/-小鼠表现出显著更高的(p<；0.05)脑梗塞体积和神经功能缺失评分(NDS)。在另一组小鼠中，给予pMCAO100 mg/kg银杏叶提取物7616 mg/kg BB、GA、GB或10 mg/kg TFM 4h后，脑梗塞体积(BB；29.0±3.9%，GA；31.3±4.0%，GB；32.0±3.8%，TFM；32.5±3.5%；761；27.4±4.5%)显著低于赋形剂组(46.0±3.7%)。BB组：7.1±1.8，GA；7.4±2.1，GB；7.9±1.8，TFM；7.7±1.7，EGb 6.8±2.0，均低于赋形剂治疗组(13.8±1.5)。有趣的是，当用银杏叶提取物761处理HO1基因敲除小鼠时，银杏叶提取物761的保护作用基本消失。在另一个队列中，EGb 761和BB组大脑皮层HO1、VEGF和eNOS蛋白水平似乎较高，而GA、GB和TFM处理组则无明显变化。综上所述，这些结果表明，HO1至少部分地在银杏叶提取物761的神经保护机制和迟发性脑缺血中发挥重要作用。以这一通路为靶点可能导致针对缺血性中风的神经保护剂。
Ginkgo biloba extract, EGb 761, a popular and standardized natural extract, contains 24% ginkgo-flavonol glycosides and 6% terpene lactones. EGb 761 is used worldwide to treat many ailments, and while a number of studies have shown its neuroprotective properties, the mechanisms of action have not been elucidated fully. We hypothesize that EGb 761 and some of its bioactive components [Bilobalide (BB), Ginkgolide A (GA), Ginkgolide B (GB), and Terpene Free Material (TFM)] could provide neuroprotection ischemic conditions through heme oxygenase 1 (HO1). Mice were subjected permanent distal middle cerebral artery occlusion (pMCAO) and survived for 7 days. HO1-/- mice showed significantly higher (p<0.05) infarct volume and Neurologic Deficit Scores (NDS) as compared to their wildtype (WT) counterparts. In another cohort, mice subjected to pMCAO and treated at 4 h of pMCAO with 100mg/kg EGb 761 6mg/kg BB, GA, GB, or 10mg/kg TFM showed significantly lower (p<0.05) infarct volumes (BB; 29.0±3.9%, GA; 31.3±4.0%, GB; 32.0±3.8%, TFM; 32.5±3.5%, and 761; 27.4±4.5%) than those in the vehicle-treated mice (46.0±3.7%). Similarly, were lower in BB: 7.1±1.8, GA; 7.4±2.1, GB; 7.9±1.8, TFM; 7.7±1.7, and EGb 6.8±2.0 groups as compared with the vehicle-treated group (13.8±1.5). Interestingly, the protective effect of EGb 761 was essentially lost when HO1 knockout mice were treated with EGb 761. In another cohort, HO1, VEGF and eNOS protein levels in the cortices appeared to be higher in EGb 761 and BB but not in GA, GB and TFM treated groups. Together, these results suggest that HO1 plays, at least in part, an important role in the neuroprotective mechanism of EGb 761 and in delayed ischemia. Targeting this pathway could lead to neuroprotective agents against ischemic stroke.
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影响因子：
8.3
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