Effects of Ginkgo Biloba Special Extract EGb 761^(█) in Very Mild Cognitive Impairment(vMCI)

Objective: To assess effects of EGb 761? on cognition and quality of life in subjects with very mild cognitive impair-ment. Methods: We randomized 300 subjects aged 45 to 65 with cognitive complaints and low functioning (more than one standard deviation below appropriate norm) in at least one cognitive test to double-blind treatment with once daily 240 mg EGb 761? or placebo for 12 weeks. Results: The exploratory intention-to-treat analysis showed significant im-provement (p < 0.025, one-sided) beyond practice effects for EGb 761? in a measure of attention (Vienna Test System - Work Performance Series) and trends in favour of EGb 761? in measures of memory (Wechsler Memory Scale III - Faces I, Appointments Test – delayed recall), and perceived physical health (SF36 - factor score Physical Health). Cognitive effects were more pronounced and more consistent (p < 0.025 in 4 of 5 tests) in subjects with lower memory function at baseline. Specifically, practice effects in the more demanding tests were attenuated or absent in these sub-jects. Conclusion: Ginkgo biloba extract EGb 761? improved cognitive functioning and aspects of quality of life in sub-jects with very mild cognitive impairment.

Ginkgo biloba Extract EGb 761® Improves Central Vestibular Vertigo in Patients Undergoing Vestibular Exercises: A Randomised Placebo-Controlled Trial

Background: Ginkgo biloba extract EGb 761® is widely used to treat various types of vertigo. Aims: An exploratory trial was conducted to evaluate the efficacy of EGb 761® in addition to vestibular exercises in central vestibular vertigo caused by vertebro-basilar ischaemia. Subjects and Methods: In this randomised, placebo-controlled, double-blind trial, 40 patients were enrolled in the vertigo clinic of a neurological university hospital and treated with daily doses of 240 mg EGb 761® or placebo for a period of 180 days. All patients regularly performed vestibular exercises in addition. Efficacy was assessed using: a visual analogue scale for the patients to rate the overall intensity of vertigo;a numeric scale for physician-rated change;a vertigo score based on intensity, duration, and frequency of vertigo;and electronystagmography. Results: Until day 180, the mean patient-rated intensity of vertigo decreased by 46% during EGb 761® treatment and by 19% with placebo (p ® group compared to the placebo group. Nystagmus or other eye movement disorders were present only in small subgroups of patients without sufficient statistical power to detect differences between treatment groups. Conclusions: EGb 761® alleviated vertigo caused by ischaemic lesions in the brainstem or cerebellum in patients undergoing vestibular exercises.

A ginkgo biloba extract promotes proliferation of endogenous neural stem cells in vascular dementia rats

The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson＇s disease model mice and in the hippocampal zone of young epileptic rats. However, it remains unclear whether EGb761 enhances proliferation of endogenous neural stem cells in the brain of rats with vascular dementia. In this study, a vascular dementia model was established by repeatedly clipping and reperfusing the bilateral common carotid arteries of rats in combination with an intraperitoneal injection of a sodium nitroprusside solution. Seven days after establishing the model, rats were intragastrically given EGb761 at 50 mg/kg per day. Learning and memory abilities were assessed using the Morris water maze and proliferation of endogenous neural stem cells in the subventricular zone and dentate gyrus were labeled by 5-bromo-2-deoxyuridine immunofluorescence in all rats at 15 days, and 1, 2, and 4 months after model establishment. The escape latencies in Morris water maze tests of rats with vascular dementia after EGb761 treatment were significantly shorter than the model group. Immunofluorescence staining showed that the number and proliferation of 5-bromo-2-deoxyuridine-positive cells in the subventricular zone and dentate gyrus of the EGb761-treated group were significantly higher than in the model group. These experimental findings suggest that EGb761 enhances proliferation of neural stem cells in the subventricular zone and dentate gyrus, and significantly improves learning and memory in rats with vascular dementia.

The Effects of Standardized Ginkgo Biloba Extracts (GBE) on Subjective Cognitive Decline (SCD) in Middle-Aged Adults: A Review

Subjective cognitive decline (SCD) is defined as the presence of self-reported cognitive complaints with unimpaired performance in neuropsychological cognitive tests. SCD has been identified as a precursor of mild cognitive impairment (MCI) and potentially represents the earliest clinical sign of Alzheimer’s disease (AD). Standardized extracts of Ginkgo biloba (GBE) are widely used as a treatment for cognitive impairment. Nonetheless, most of the available review articles focus on the effects of GBE in MCI and dementia but not in SCD and its specific cognitive effects. Thus, this review collects and discusses the available published clinical data for the effects of standardized GBE on the early stages of cognitive decline among an age group where SCD becomes a topic—the middle-aged adults. Randomized clinical trials (RCTs), systematic reviews and meta-analyses of standardized GBEs in cognitive decline subjects were searched using PubMed/MEDLINE, Science direct, Cochrane, and Google Scholar until January 2019. Data from relevant RCT were critically evaluated to determine the potential effects of GBE on SCD. The results showed that the number of available GBE studies on SCD is small. Eight studies were selected in which subjects reported memory impairment, in some cases with concerns (worries), and with an average age at onset SCD of 60 years. Six studies gave a proof of efficacy for GBE for the treatment of SCD in at least one cognitive parameter. One study is inconclusive, however, a post-hoc analysis demonstrates efficacy in preventing AD with intake >4 years. The most common GBE dosage used was 240 mg GBE/day over a minimum period of 8 weeks. Hence, there might be beneficial effects of GBE to prevent, improve or delay SCD in the generation of 50 years or older. However, larger, well-defined RCTs using SCD criteria are necessary to further substantiate this effect in SCD subjects.

Effects of Ginkgo biloba extract on expression of biomarkers during aflatoxin B_1-induced hepatocarcinogenesis in Wistar rats

Objective： The aim of this study was to study the effect of Ginkgo biloba extract （EGb761） on metabolism of afiatoxin B1 （AFB1） in Wistar rats. Methods： Seventy one Wistar rats were assigned at random to groups A, B and C. Rats in groups A, B were injected with AFB1 （intraperitoneal, 100-200 ug/kg body weight, 1-3 times/week）. Group C was normal control. Rats in group B were fed in food with EGb761, while rats in groups A, C were given normal food. Blood samples were collected and liver biopsies were performed on the 14th, 28th and 42nd week. All the rats were sacrificed on the 64th week. The incidence of hepatocarcinoma was investigated. The hepatic phase I drug-metabolizing enzyme Cytochrome-P450 （CYP450） and phase II metabolizing enzyme glutathione S-transferase （GST） were analyzed with spectrometry. Serum AFB1- lysine adduct levels were assessed with high performance liquid chromatography （HPLC）. The expression of 8-hydroxydeoxy- guanosine （8-OHdG） was measured with immunohistochemistry. Results： The incidence of hepatocellular carcinoma （HCC） in group B was significantly lower than that in group A （26.92% vs 76.00%, P 〈 0.001）. No HCC developed in group C. EGb761 showed no effects on the activities of CYP450 and GST in rat liver tissues. The level of AFB1-lysine adduct reached the peak （4356.01 pg/mg albumin） at the 14th week in group A. EGb761 significantly inhibited the formation of AFB1-lysine adduct in serum by 13.07% at the 14th week （P = 0.033）, and 73.63% at the 42nd week （P = 0.002）. The expression of 8-OHdG protein in rat liver tissues in group B was significantly lower than that in group A at the 28th, 42nd, and 64th week （P 〈 0.05）. Conclusion： The main mechanism underlying the effect of EGb761 in blocking hepatocarcinogenesis induced by AFB1 may not be fully attributable to its influence on the activity of liver phase I and phase II metabolizing enzymes. EGb761 inhibits the production of AFB1-lysine adducts, decreases the expression of 8-OHdG protein, and finally alleviates the DNA oxidative injury, which may be one of the mechanisms for the effects of EGb761 in inhibiting or delaying AFB1-induced hepatocarcinogenesis.

丹酚酸B和银杏叶提取物EGb761对β-淀粉样蛋白神经毒性抑制作用的比较

目的比较丹酚酸B(Sal B)和银杏叶提取物EGb 761对β-淀粉样蛋白(β-AP)纤维形成及细胞毒作用的影响。方法运用硫黄素T(ThT)荧光法和电子显微镜技术分析Sal B和EGb 761对β-AP1-40聚集和纤维形成的影响;另将β-AP25-35预先老化7 d,用MTT法和流式细胞仪检测两种提取物对此老化蛋白造成的PC12细胞毒性的保护作用,用荧光法观察β-AP25-35作用后细胞内活性氧含量的变化以及两种提取物的作用。结果Sal B和EGb 761都可有效地抑制β-AP1-40纤维的形成,明显抑制老化的β-AP25-35对PC12细胞的毒性作用,降低β-AP25-35造成的细胞内活性氧含量的增加。Sal B的有效剂量远远低于EGb 761。结论Sal B对β-AP神经毒性的抑制作用强于EGb 761。

银杏叶提取物EGb761对兔视网膜缺血损伤的保护作用

目的:研究自由基清除剂EGb761对实验性视网膜缺血前后的图形视网膜电图(P-ERG)和形态学的影响,探讨EGb761抗氧化作用及视网膜缺血损伤的发病机制。方法:升高新西兰白兔眼压至130mmHg持续60min来诱导视网膜缺血,实验组动物给予EGb761,对照组动物给予生理盐水,在缺血前、中、后记录P-ERG波幅变化,并在再灌注19h摘除眼球,作光镜、电镜形态学观察。结果:缺血60min再灌注19h引起b波振幅降低,视网膜神经节细胞、内核层细胞缺失(调亡、坏死),给予EGb761后可以改善b波的恢复,并可抑制或减少视网膜细胞损害。结论:自由基清除剂EGb761可改善视网膜缺血损伤的功能恢复。

EGb761对慢性低氧低糖培养的大鼠海马神经元β分泌酶的影响

目的研究银杏叶制剂EGb761(金钠多)对慢性低氧低糖培养大鼠海马神经元β分泌酶的影响,探讨其防治痴呆的可能机制。方法取新生24h的Wistar大鼠海马神经元原代培养,培养第7d行低氧低糖培养和EGb761(金纳多100ug/ml)药物干预,以荧光法检测β分泌酶活性,Western blot检测β分泌酶BACE1蛋白表达。结果低氧低糖培养12h、24h、36h组海马神经元较正常培养对照组β分泌酶活性升高(P<0.05);金纳多药物干预12h、24h、36h组与相应时间非药物干预组相比海马神经元β分泌酶活性降低(P<0.05)。低氧低糖培养12h、24h、36h组海马神经元β分泌酶BACE1表达水平升高(P<0.05);金纳多药物干预12h、24h、36h组与相应时间非药物干预组相比β分泌酶BACE1表达水平降低(P<0.05)。结论金钠多对慢性低氧低糖培养海马神经元β分泌酶活性和表达的影响是其防治痴呆的可能机制之一。

银杏叶提取物EGb-761对乳腺癌肺转移型小鼠体内实体瘤的影响

目的:探讨银杏叶提取物EGb-761对乳腺癌肺转移型小鼠体内实体瘤的影响。方法:选取雌性BALB/c小鼠,使用小鼠乳腺癌4T1细胞系建立高转移性的肿瘤小鼠模型,随机分为五组,即正常组、模型组、EGb-761组[高剂量组(200 mg/kg)、中剂量组(100 mg/kg)、低剂量组(50 mg/kg)]。观察并测量各组小鼠原位灶实体瘤体积和小鼠体质量;观察并计算各组小鼠肺部转移灶结节数、转移率;采用RT-PCR法检测各组小鼠特异性标志物角蛋白-19(CK-19)mRNA表达。结果:随着EGb-761剂量的增加,小鼠原位灶实体瘤体积越来越小,而小鼠体质量越来越重(P<0.05);随着EGb-761剂量的增加,肺部结节数随之减少(P<0.05),肺部转移率随之降低(P<0.05);随着EGb-761剂量的增加,肺组织CK-19 mRNA表达量越低(P<0.05)。结论:银杏叶提取物(EGb-761)对乳腺癌肺转移型小鼠体内的实体瘤生长有抑制作用。

银杏叶提取物联合多奈哌齐对阿尔茨海默病模型大鼠的协同作用及其机制

目的探讨银杏叶提取物(EGb 761)联合多奈哌齐对阿尔茨海默病(AD)模型大鼠的协同作用及其机制。方法取雄性SD大鼠72只,随机分为正常组(等体积生理盐水)、假手术组(等体积生理盐水)、模型组(等体积生理盐水)、多奈哌齐组(25 mg/kg)、EGb 761组(50 mg/kg)和联合组(多奈哌齐25 mg/kg+EGb 76150 mg/kg),各12只。腹膜内注射水合氯醛300 mg/kg麻醉,将聚集的Aβ25-35(10μL)以1μL/min的速率注入大鼠双侧海马,以复制AD大鼠模型。建模成功后,各组大鼠均灌胃相应药物或生理盐水,每天1次,共2个疗程(每个疗程10 d,间隔3 d)。采用Morris水迷宫实验评估大鼠的认知和记忆能力;采用TUNEL染色法,观察大鼠海马神经细胞凋亡情况,并计算凋亡指数;采用酶联免疫吸附法检测大鼠血清乙酰胆碱酯酶(AChE)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平;采用Western blot法检测大鼠海马组织中核因子(NF)-κB通路相关蛋白p-IKKα,p-IκBα,p-NF-κB表达水平。结果与模型组比较,各给药组大鼠Morris水迷宫实验第6天逃避潜伏期均大幅缩短,第7天各给药组大鼠在象限Ⅰ中穿越平台的次数及耗时百分比均显著增加;各给药组大鼠海马神经细胞阳性数量均显著减少,凋亡指数均显著降低(P<0.05);各给药组大鼠AChE和MDA水平均显著降低,SOD水平显著升高(P<0.05);各给药组大鼠NF-κB通路相关蛋白p-IKKα,p-IκBα,p-NF-κB的表达水平均显著升高(P<0.05);且联合组上述指标变化均更显著(P<0.05)。结论EGb 761联合多奈哌齐可协同改善AD模型大鼠的记忆能力,其机制可能与减少海马神经细胞NF-κB通路激活后的细胞凋亡有关。

银杏叶提取物761对矽肺大鼠的防护作用

目的探讨银杏叶提取物761(Ginkgo biloba Extract 761,EGb761)对矽肺大鼠的肺保护作用。方法采用二氧化硅悬液气管内灌注法建立矽肺大鼠模型。二氧化硅灌注1 d后,每日灌服EGb761,持续4周。处死大鼠,收集肺组织。HE和Van Gieson(VG)染色法观察肺组织病理形态学情况,采用ELISA法检测肺组织中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白介素6(interleukin 6,IL-6)和IL-1β的水平,采用免疫组织化学染色和Western blot法检测肺组织中α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、Ⅰ型胶原蛋白(typeⅠcollagen,COLⅠ)、纤维连接蛋白(fibronectin,FN)以及结缔组织生长因子(connective tissue growth factor,CTGF)的表达水平。结果EGb761可改善由二氧化硅诱导的肺纤维化,缓解肺部炎症,减轻肺泡损伤,减少胶原沉积,下调促炎因子和纤维化相关因子的表达。结论EGb761干预可改善二氧化硅诱导的矽肺大鼠的肺纤维化和肺损伤。

Hyperbaric Oxygen and Ginkgo Biloba Extract Ameliorate Cognitive and Memory Impairment via Nuclear Factor Kappa-B Pathway in Rat Model of Alzheimer＇s Disease

Background： Hyperbaric oxygen （HBO） and Ginkgo biloba extract （e.g., EGB 761） were shown to ameliorate cognitive and memory impairment in Alzheimcr＇s disease （AD）. However, the exact mechanism remains elusive. The aim of the present study was to investigate the possible mechanisms of HBO and EGB 761 via the function of nuclear factor kappa-B （NF-κB） pathway. Methods： AD rats were induced by injecting β-amyloid 25-35 into the hippocampus. All animals were divided into six groups： Normal. sham. AD model, HBO （2 atmosphere absolute： 60 min/d）, EGB 761 （20 mg·kg^-1 ·d ^-1）, and HBO/EGB 761 groups. Morris water maze tests were used to assess cognitive, and memory capacities of rats： TdT-mediated dUTP Nick-End Labeling staining and Western blotting were used to analyze apoptosis and NF-κB pathway-related proteins in hippocampus tissues. Results： Morris water maze tests revealed that EGB 761 and HBO significantly improved the cognitive and memory ability of AD rats. In addition, the protective effect of combinational therapy （HBO/EGB 761 ） was superior to either HBO or EGB 761 alone. In line. redticed apoptosis with NF-κB pathway activation was observed in hippocampus neurons treated by HBO and EGB 761. Conclusions： Our results suggested that HBO and EGB 761 improve cognitive and memory capacity in a rat model of AD. The protective effects are associated with the reduced apoptosis with NF-κB pathway activation in hippocampus neurons.

银杏叶提取物速释滴丸的研制

目的 :研究银杏叶提取物速释滴丸的处方和滴制工艺。方法 :分别以银杏总黄酮溶出百分量和丸重差异为评价指标 ,采用正交试验进行处方和工艺优化。结果 :优化结果表明 ,滴丸平均T50 为 3.6 2min ,平均丸重差异为2 .80 %。结论 :所研制的银杏叶提取物速释滴丸能明显提高有效成分的溶出速率 。

银杏叶提取物对柑橘青霉病菌的抑菌效果

研究银杏叶乙醇提取物(EGb)对储藏期柑橘青霉病菌的抑菌作用。采用95%乙醇提取银杏叶,用针刺伤柑橘后以青霉病菌菌液和EGb处理柑橘进行药效试验,测试EGb对柑橘青霉病菌的抑菌效果。结果表明,EGb对储藏期柑橘青霉病菌具有较强的抑菌作用,且随着EGb浓度的增大抑菌作用增强,随着储藏时间的延长,EGb的抑菌作用降低。

银杏叶提取物抗肿瘤机制研究进展

银杏叶提取物已被广泛应用于治疗心血管和外周血管灌注不足、过敏性疾病和神经性疾病等,最近研究证明银杏叶提取物对多种肿瘤具有抑制作用,其机制主要包括诱导凋亡、抗氧化和免疫调节等,银杏叶提取物抗肿瘤作用的具体研究对指导临床预防和治疗肿瘤有重要意义,对目前银杏叶提取物的抗肿瘤机制做一综述。

银杏叶提取物对高脂饮食大鼠胰岛素敏感性的影响

目的观察银杏叶提取物对高脂饮食诱导的胰岛素抵抗大鼠胰岛素敏感性的影响。方法采用高脂喂养的方法建立胰岛素抵抗大鼠动物模型,舒血宁腹腔注射进行干预,以罗格列酮作为阳性对照。干预前后分别行高胰岛素-正葡萄糖钳夹实验测定葡萄糖输注率(GIR),并测定血清总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)、空腹胰岛素(FINS)、空腹血糖(FBG)等指标。结果高脂喂养成功复制了胰岛素抵抗大鼠模型,第4周即出现GIR下降,与正常对照组相比,差异显著(P<0.05);随时间延长,GIR降低更加明显;TC、TG、FFA、FBG、FINS不同程度升高(P<0.05或P<0.01);银杏叶提取物干预使上述指标明显改善(P<0.05或P<0.01),与罗格列酮干预作用相近。结论银杏叶提取物可以显著改善高脂诱导的大鼠胰岛素抵抗状态,其作用可能与调节血脂及游离脂肪酸代谢有关。

银杏叶提取物对马兜铃酸肾病管周毛细血管病变的治疗作用

目的研究马兜铃酸肾病管周毛细血管(peritubularcapillaries,PTCs)损害以及银杏叶提取物(EGB)对其治疗作用。方法将20只雌性Wister大鼠先用关木通煎剂灌胃8周,然后随机分为治疗组(10只)和未治疗组(10只)。治疗组再予EGB灌胃治疗8周;未治疗组予饮用水灌胃8周。另设正常对照组8只。第16周处死全部大鼠,留取尿、血和肾组织标本,分别作病理、免疫组化CD34抗体标记、生化等检查。结果与正常对照组和治疗组相比,未治疗组大鼠间质微血管病变严重,PTCs密度明显减少(P<0.01),肾功能明显损害(P<0.01),肾小管萎缩明显,肾小管面积明显缩小(P<0.01),肾间质面积明显增加(P<0.01),肾间质严重纤维化。EGB能明显延缓马兜铃酸肾病的进展,减轻微血管病变,改善肾小管萎缩程度,保护肾功能。PTCs密度与血肌酐(Scr)水平、肾间质面积呈负相关(P<0.001),与近端小管面积呈正相关(P<0.001)。结论马兜铃酸肾病PTCs损伤严重,EGB治疗能明显改善PTCs损伤程度,保护肾功能。

银杏叶提取物对肉鸡生产性能、屠宰性能和免疫指标的影响

将240只1日龄健康AA肉仔母雏随机分成4个处理,每个处理3个重复,每个重复20只鸡,试验期35天.对照组饲喂基础日粮,试验1-3组分别在基础日粮中添加0.6%、0.8%、1.0%银杏叶提取物(EGB),研究EGB对肉鸡生产性能、屠宰性能和免疫指标的影响.结果表明:0.8%EGB显著提高肉鸡后期增重和饲料转化率,显著降低肉鸡腹脂率(P<0.05);肉鸡屠宰率随着EGB添加水平的增加呈提高的趋势(P>0.05);1.0%EGB显著提高肉鸡全净膛率;0.8%、1.0%EGB显著提高肉鸡法氏囊指数、胸腺指数和新城疫抗体滴度(P<0.05);1.0%EGB显著提高肉鸡血清球蛋白和IgG含量(P<0.05).可见,在本试验条件下,日粮中添加一定水平的EGB对肉鸡产肉性能和免疫性能有一定的促进作用.

银杏叶提取物对坐骨神经再生的影响

目的:研究银杏叶提取物局部应用对坐骨神经再生的影响。方法:选Wistar大鼠32只,随机分为银杏叶提取物组和对照组。在双目放大镜下切断两组大鼠右侧坐骨神经,于神经损伤处和周围肌肉间隙内注射药物后立即行缝合术。2周后进行坐骨神经功能指数、电生理学和组织形态学观测评定。结果:银杏叶提取物组各项指标均优于对照组,其坐骨神经功能指数的恢复、神经纤维的生长速度及数量明显优于对照组。结论:银杏叶提取物局部应用可有效促进大鼠坐骨神经损伤的早期再生,加快神经再生速度与神经功能恢复。