银杏叶提取物EGb761对大鼠脊髓损伤后的神经保护作用

目的探讨银杏叶提取物EGb761对实验性大鼠脊髓损伤后神经保护的作用及其机制。方法成年雄性SD大鼠132只,体重200～250 g,随机分为正常对照组（N组）、损伤组（T组）、甲基强的松龙治疗组（MP组）和EGb761治疗组（EGb761组）,每组33只。T组、MP组、EGb761组用改良Allen法以25GCF损伤力度致伤大鼠,建立T9脊髓中度损伤模型。术后4、8、24 h每组随机取3只动物切取损伤区1 cm脊髓节段,分别用黄嘌呤氧化酶法和硫代巴比妥酸（TBA）法测定脊髓组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量。分别于术后24 h、3、5、7、14 d处死动物（n=6）,快速取T9节段脊髓,TUNEL法标记细胞凋亡,免疫组化方法检测诱生型一氧化氮合酶（iNOS）的表达。结果术后4、8、24 h EGb761治疗组SOD活性及MDA含量与损伤对照组比较均差异有显著性（P〈0.01）。术后各时相点EGb761治疗组神经细胞凋亡指数和iNOS表达阳性细胞率均低于损伤对照组（P〈0.01或P〈0.05）。结论 EGb761能抑制脊髓损伤后的脂质过氧化反应,减轻神经细胞的凋亡,其机制可能与抑制iNOS表达有关。     

银杏叶提取物预防在体心肌缺血再灌注损伤

目的：探讨中药成份银杏叶提取物（ginkgo biloba extract,EGb 761)在体心肌缺血再灌注损伤中的作用及其机制。方法：以在体大鼠心肌缺血再灌注为模型,分别于再灌注前10min静脉给予生理盐水或不同剂量的EGb761,检测缺血再灌区心肌组织现二醛（MDA）、一氧化氮（NO）含量。结果：缺血再灌注使相应区域心肌MDA、NO含量上升,EGb761治疗组心肌MDA、NO含量下降,但下降程度与EGb761剂量不呈量效关系。结论：EGb761通过抗氧自由基和清除一氧化氮能预防在体心肌缺血再灌注损伤。     

慢性脑缺血大鼠脑星形胶质细胞反应性增生及EGb761的影响

目的 探讨EGb761(银杏叶提取物)对慢性脑缺血损伤后大鼠脑组织星形胶质细胞反应性增生的影响.方法 将雄性SD大鼠随机分为假手术组、单纯缺血组、EGb761干预组.制备慢性脑缺血大鼠模型,药物干预12周后,免疫组化方法检测各组大鼠脑组织中星形胶质细胞的表达.结果 EGb761干预组大鼠海马、胼胝体、皮质GFAP阳性细胞表达明显低于单纯缺血组,差异有统计学意义(P＜0.05).结论 EGb761可减少慢性脑缺血损伤后反应性星形胶质细胞增生.     

自身免疫性、多发性周围神经病患者的免疫球蛋白和银杏制剂对体外培养的SD大鼠雪旺氏细胞生长的影响

目的：明确自身免疫介导的多发性周围神经病患者血清中的免疫球蛋白（immunoglobulin,Ig)是否具有破坏雪旺氏细胞（Schwann cell,Sc)的作用；银杏制剂（Extract of Ginkgo biloba 761,EGb761)在这种情况下是否具有保护Sc的作用。方法：在离体培养的雪旺氏细胞中分别加入正常人和自身免疫性周围神经病患者的Ig、Ig和EGb761的混合液，观察雪旺细胞的形态学变化。结果：正常人的Ig对Sc的生长无影响；患者的Ig对体外培养的Sc的生长有抑制作用。EGb761对Sc的生长无显著影响。结论：自身免疫性周围神经病患者的Ig在补体的参与下对体外培养的Sc有明显的破坏作用。银杏制剂在这种情况下似乎无显著的保护体外Sc继续生长的作用。     

银杏叶提取物EGb761对NO供体硝普钠诱导的海马神经元凋亡的保护作用

目的　探讨银杏叶提取物(EGb 761 )对NO供体硝普钠(SNP)引起的大鼠海马神经元凋亡的影响。方法　采用MTT比色分析测细胞存活率、Hoechst 332 58荧光染色及DNA琼脂糖凝胶电泳分析等方法检测凋亡。结果　不同剂量EGb761预处理海马神经元6h可剂量依赖地对抗SNP引起的神经元凋亡,提高神经元的存活率;减少SNP引起的核固缩、凝聚和碎裂现象;DNA凝胶电泳图谱未见典型的“梯子状”改变。结论　EGb 761对NO供体SNP诱导的海马神经元凋亡具有明显的保护作用     

银杏叶提取物EGb761对NO供体硝普钠诱导的海马神经元凋亡的保护作用

目的　探讨银杏叶提取物 (EGb 761 )对NO供体硝普钠 (SNP)引起的大鼠海马神经元凋亡的影响。方法　采用MTT比色分析测细胞存活率、Hoechst 332 58荧光染色及DNA琼脂糖凝胶电泳分析等方法检测凋亡。结果　不同剂量EGb761预处理海马神经元 6h可剂量依赖地对抗SNP引起的神经元凋亡 ,提高神经元的存活率 ;减少SNP引起的核固缩、凝聚和碎裂现象 ;DNA凝胶电泳图谱未见典型的“梯子状”改变。结论　EGb 761对NO供体SNP诱导的海马神经元凋亡具有明显的保护作用     

银杏叶提取物EGb 761对N0供体硝普钠诱导的海马神经元凋亡的保护作用

目的 探讨银杏叶提取物(EGb 761)对NO供体硝普钠(SNP)引起的大鼠海马神经元凋亡的影响。方法 采用MTT比色分析到细胞存活率、Hoechst 33258荧光染色及DNA琼脂糖凝胶电泳分析等方法检测凋亡。结果 不同剂量EGb761预处理海马神经元6h可剂量依赖地对抗SNP引起的神经无凋亡，提高神经元的存活率；减少SNP引起的核固缩、凝聚和碎裂现象；DNA凝胶电泳图谱未见典型的“梯子状“改变。结论 EGb 761对NO供体SNP诱导的海马神经元凋亡具有明显的保护作用。     

银杏磷脂复合物的研究进展

目的：通过对银杏叶提取物（EGb761）研究现况的分析，找出提高EGb761口服制剂临床疗效的途径。方法：对EGb761的研究现况、药理作用、临床疗效及口服制剂中加入大豆卵磷脂提高银杏酮酯疗效的分析。结果：EGb761在治疗心脑血管疾病中有效，而且银杏磷脂复合物的药理作用明显强于等剂量的杏灵颗粒和银杏磷脂混合物。结论：EGb761口服制剂中加入大豆卵磷脂能够明显提高银杏酮酯的生物利用度，从而提高EGb761口服制剂的临床疗效。     

银杏叶提取物对db/db糖尿病小鼠胰岛功能的影响

目的探讨银杏叶提取物EGb761对胰岛分泌功能的影响及相关机制。方法 10只8周龄db/db小鼠随机分为两组,观察组(EGb761组)和糖尿病对照组(db/db组),每组各5只,分别给予EGb761 100 mg/(kg.d)和安慰剂灌胃。另选5只同周龄db/m小鼠给予安慰剂灌胃作为非糖尿病对照(db/m组)。每周监测体重、血糖,8周后行腹腔葡萄糖耐量试验并取胰腺行免疫组化检测,分析胰岛内烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate,NADPH)氧化酶表达情况。结果 EGb761组血糖、胰岛素分泌功能和胰岛素敏感性、胰岛内NADPH氧化酶gp91phox、p22phox亚基的表达水平、胰岛质量显著改善。结论 EGb761能够降低NADPH氧化酶的表达,减少氧化应激的来源,改善胰岛微环境,从而保护胰岛β细胞。     

银杏叶提取物EGb761对阿米卡星所致离体豚鼠耳蜗外毛细胞内钙和运动性变化的影响

利用激光共聚焦成像系统和荧光探针Fluo 3/AM监测离体单个豚鼠耳蜗外毛细胞 (OHC)内游离钙浓度 ([Ca2 + ]i)的变化 ,以及显微摄像记录OHC的运动情况 ,发现阿米卡星 (AK ,4 .76g·L- 1)使OHC[Ca2 + ]i 显著下降 ,伴随着细胞可逆性的缩短变粗 ,恢复后 ,细胞仍比正常短胖 ,胞膜折皱 ,核固缩 .银杏叶提取物EGb761(0 .2g·L- 1)在AK前或后加入均不能中断 [Ca2 + ]i 下降及细胞收缩这一过程 ,但可以使AK所致的极低 [Ca2 + ]i 回升 .此外 ,EGb761可以改善AK对OHC形态的不可逆损伤 .结果提示 ,AK所致的 [Ca2 + ]i 下降可破坏OHC慢运动 ,而EGb761对AK所致OHC损伤有一定拮抗作用 .     

EGb 761: ginkgo biloba extract,Ginkor

EGb 761 [Ginkgo biloba extract EGb 761, R?kan, Tanakan, Tebonin] is a standardised extract of Ginkgo biloba leaves and has antioxidant properties as a free radical scavenger. A standardised extract of Ginkgo biloba leaves is a well defined product and contains approximately 24% flavone glycosides (primarily quercetin, kaempferol and isorhamnetin) and 6% terpene lactones (2.8-3.4% ginkgolides A, B and C, and 2.6-3.2% bilobalide). Ginkgolide B and bilobalide account for about 0.8% and 3% of the total extract, respectively. Other constituents include proanthocyanadins, glucose, rhamnose, organic acids, D-glucaric and ginkgolic acids. EGb 761 promotes vasodilation and improves blood flow through arteries, veins and capillaries. It inhibits platelet aggregation and prolongs bleeding time. EGb 761, which was originated by Dr Willmar Schwabe Pharmaceuticals (Dr Willmar Schwabe Group), has been available in Europe as a herbal extract since the early 1990s. However, products containing EGb 761 are not approved for use by the US FDA. As a dietary supplement, Nature's Way in the US distributes and markets a standardised extract of Ginkgo biloba leaves (the EGb 761 Formula) under the name Gingold Nature's Way. The French company Beaufour-Ipsen and its German subsidiary Ipsen Pharma are co-developing EGb 761 with Dr Willmar Schwabe Group. Beaufour-Ipsen (France) is developing EGb 761 as Tanakan, Dr Willmar Schwabe Pharmaceuticals (Germany) as Tebonin and Ipsen Pharma (Germany) as R?kan. Intersan was formerly developing EGb 761 in Germany, but Intersan appears to have been merged into Ipsen Pharma. However, there has been no recent development for these indications. In the UK and other European countries, the cardioprotective effects of EGb 761 in myocardial ischaemia and reperfusion are being investigated in preclinical studies. The psychological and physiological benefits of ginkgo are said to be based on its primary action of regulating neurotransmitters and exerting neuroprotective effects in the brain, protecting against or retarding nerve cell degeneration. Ginkgo also benefits vascular microcirculation by improving blood flow in small vessels and has antioxidant activity. There has been conflicting evidence about the benefits of ginkgo, e.g. the ginkgo clinical trial published in August 2002 in JAMA concluded that a leading ginkgo supplement did not produce measurable benefits for memory in healthy adults over 60, although a month earlier, another study concluded that the same ginkgo extract is effective in helping normal healthy older adults in memory and concentration. However, in December 2002, the Cochrane Collaboration, the world's most respected scientific reviewer of clinical trials in medicine, concluded that the published literature strongly supports the safety and potential benefits of ginkgo in treating memory loss and cognitive disorders associated with age- related dementia. A phase II study of EGb 761 in combination with fluorouracil is in progress in Germany in patients with pancreatic cancer. German researchers are investigating the potential of EGb 761 for the treatment of sudden deafness and tinnitus in clinical studies. EGb 761 was undergoing preclinical development for the potential treatment of diabetes in France, diabetic neuropathies in Russia, and cancer in Brazil. However, there has been no recent development for these indications. Beaufour-Ipsen has expressed the intention to license out its diabetes projects that may include EGb 761.     

Effect of the Ginkgo biloba extract, EGb 761, on memory formation in day-old chicks

Previous studies indicate that the Ginkgo biloba extract, EGb 761, has a facilitative effect on deficient memory. The temporal parameters of this effect, however, have not been clearly defined or distinguished from the effect on normal memory. The aim in the current study was to investigate the effects of EGb 761 on memory using a well-controlled animal model. Day-old chicks were trained on either a weakly or strongly reinforced version of a passive avoidance task. Long-term memory formation of the weakly reinforced version of the task was improved significantly by EGb 761 (3 mg/ml) when administered between 10 and 30 min after training. However, the same dose of EGb 761 impaired retention when administered prior to strongly reinforced training. These data provide convincing evidence that posttraining administration of EGb 761 initiates long-term memory in chicks with only short-term memory, but that the same dose-administered pretraining can be deleterious for normal retention. This dual effect has important implications for the clinical use of Ginkgo biloba extracts.     

Hydrogen peroxide-induced oxidative damage and apoptosis in cerebellar granule cells: protection by Ginkgo biloba extract.

The ability of oxidative stress to induce apoptosis and the protective effects of Ginkgo biloba extract (EGb761) against this induction were studied in cultures of rat cerebellar granule cells. Cells were exposed to oxidative stress by treatment with 50 microm hydrogen peroxide+100 microm ferrous sulphate which generates hydroxyl radicals by Fenton reaction. Both morphological observation and biochemical analysis revealed that H(2)O(2)/FeSO(4)treatment induced apoptotic cell death in cerebellar granule cells, which was characterized by chromatin condensation and DNA fragmentation. During this process, the fluidity of the cell membrane decreased markedly, and the conformation of membrane proteins altered significantly. Pretreating cerebellar granule cells with the antioxidant EGb761 (Ginkgo biloba extract) effectively attenuated oxidative damage induced by H(2)O(2)/FeSO(4), and prevented cells from apoptotic cell death. The results suggested that EGb761 might be used as a potential drug for neuronal diseases associated with the excessive production of reactive oxygen species.     

Effect of Ginkgo biloba extract EGb 761 on the nonspecific and humoral immune responses in a hypothalamic-pituitary-adrenal axis activation model

We evaluated the immune response of healthy control and stressed Wistar rats submitted to hypothalamic-pituitary-adrenal (HPA) axis activation. Rats were treated with Ginkgo biloba extract (EGb 761) orally (100 mg/kg per day for 7 days). EGb 761 stimulated the digestion index of peritoneal and alveolar macrophages (PM and AM) of stressed rats. Likewise, the cellular immune response measured using the delayed-type hypersensitivity response to sheep red blood cells (SRBC) and the humoral immune response (measured through an anti-SRBC response), were also restored in stressed rats. Thus, this G. biloba extract possesses immunostimulatory activity in addition to its broad spectrum of pharmacological effects.     

Influence of the Ginkgo extract EGb 761 on rat liver cytochrome P450 and steroid metabolism and excretion in rats and man

Extracts from leaves of Ginkgo biloba L. are among the most used herbal medicinal products worldwide. Based on in-vitro tests and studies in rats, concern has been expressed that intake of Ginkgo extracts may affect hepatic metabolism of xenobiotics and cause drug interactions, although no evidence for modulation of cytochrome P450 (CYP450) enzyme activity was obtained in human trials. Because of these contradictory findings, we investigated the effects of the standardised extract EGb 761 on hepatic CYP450 in rats. EGb 761 (100 mg kg-1 daily, p.o., for 4 days) strongly increased liver CYP450 content and altered the ex-vivo biotransformation of androstendione, as well as metabolism of endogenous steroids. However, in human subjects no effect on the urinary steroid profile was observed after intake of EGb 761 for 28 days (240 mg daily). These results indicate that the effects of EGb 761 on drug metabolising enzymes are specific for rats and may not be extrapolated to man.     

Ginkgo biloba extract EGb 761® versus pentoxifylline in chronic tinnitus: a randomized,double-blind clinical trial

International Journal of Clinical Pharmacy - Background Ginkgo biloba extract EGb 761® and pentoxifylline are frequently prescribed for the treatment of tinnitus. Objective To compare the...     

Effects of an extract of Ginkgo biloba on learning and memory in mice

The effects of an extract of Ginkgo biloba (EGb 761) on acquisition, performance, and retention of mice in an appetitive operant conditioning were investigated. The animals were trained for 30 consecutive days to acquire a two-lever response sequence followed by food reward. EGb 761 was administered daily at a dose level of 100 mg/kg PO. Drug treatment started four and eight weeks before the training and was maintained until a retention test 10 weeks after it. The results indicated that EGb 761 facilitated memory processes. EGb 761 quickened the acquisition and improved the performance of the two-response sequence: The number of correct responses was increased and correct responses were performed more frequently in the most effective manner. Besides, incorrect responses were reduced sooner and faster and to a lower level in EGb 761-treated mice. With regard to the retention EGb 761 improved the retrieval of the learned response.     

Effects of Ginkgo biloba extract (EGb 761) on the guinea pig vestibular system.

Previous studies have demonstrated that the administration of Ginkgo biloba extract (EGb 761) improves the compensation of the vestibular syndrome induced by transection of the VIIIth nerve. To investigate the mechanisms at play, the vestibular nuclei of alert guinea pigs were perfused with EGb 761. This perfusion always induced a stereotyped reversible postural syndrome that was the mirror image of the syndrome provoked by the unilateral lesion of the otolithical receptors. This result supports the hypothesis that EGb 761 has a direct excitatory effect on the lateral vestibular nuclei (LVN) neurons. In a second step, we quantified the horizontal vestibuloocular reflex (HVOR) of the normal guinea pig following IP injection of EGb 761. In normal guinea pig, IP administration of EGb 761 led to a reversible, dose-dependent decrease of the HVOR gain without affecting the phase of the reflex. These data help to explain the therapeutic effects of EGb 761 during vestibular syndromes and strongly suggest an impact at the neuronal level.