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.

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。

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.

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。

银杏叶提取物延迟预处理对大鼠心肌缺血再灌注时细胞色素c氧化酶表达的影响

目的:探讨银杏叶提取物(EGb761)延迟预处理对大鼠心肌缺血再灌注时细胞色素c氧化酶(cytochrome coxidase,CcO)表达的影响。方法:健康成年Sprague-Dawley雄性大鼠40只,随机分成4组:S组(假手术组),仅开胸并分离冠状动脉左前降支,但不阻断血流150 min;IR组(缺血再灌注组),行冠状动脉左前降支阻断30 min,再灌注120 min;M组(银杏叶提取物延迟预处理组),予以静脉注射银杏叶提取物EGb761 100 mg/kg,给药后24 h同IR组处理;D组[银杏叶提取物预处理+5-羟葵酸(5-HD)组],缺血前15 min静脉注射5-HD 5 mg/kg,余同M组处理。再灌注结束后测心肌CcO的表达和心肌梗死面积,观察心肌细胞超微结构。结果:与IR组[(37.87±5.92)%]比较,M组[(23.78±4.82)%]心肌梗死面积减小(P<0.05),D组[(39.62±5.18)%]差异无统计学意义(P>0.05)。与S组比,IR组、M组和D组CcO均升高(P<0.05);与IR组比,M组CcO增高(P<0.05)。电镜下,M组心肌细胞损伤程度较IR组减轻,D组与IR组差异无统计学意义(P>0.05)。结论:银杏叶提取物延迟预处理对大鼠心肌的保护作用与上调心肌CcO表达有关。

银杏蜜环口服溶液改善犬急性心肌缺血的研究

目的:观察银杏蜜环口服溶液对犬急性心肌缺血的保护作用。方法:36只犬随机分为6组,模型组,合心爽组(5.0 mg/kg);天麻蜜环粉组(100 mg/kg);银杏提取物组(3.0 mg/kg);银杏蜜环口服溶液高剂量组(206 mg/kg)和银杏蜜环口服溶液低剂量组(103 mg/kg)。通过结扎犬冠状动脉前降支的方法复制急性心肌缺血模型。观察心肌缺血后不同时间点冠状动脉血流量、血氧含量、心肌耗氧量及心肌氧利用度,心肌梗死范围的变化。结果:与模型组比较,银杏蜜环口服溶液大、小剂量组以及蜜环粉组和银杏提取物组心肌梗死范围明显下降(P<0.05);同时银杏蜜环口服溶液高剂量组在缺血后30 min静脉血氧含量明显下降(P<0.05),在缺血后15、30、60 min心肌耗氧量和心肌氧利用度明显增加(P<0.05),在缺血后60~180 min时冠状动脉血流量明显升高(P<0.05)。结论 :银杏蜜环口服溶液可在心肌急性缺血状态下短期内促进心肌氧供给和氧消耗;有效增加冠脉血流量,增加心肌的供血供氧,提高心肌氧利用度。药效作用优于银杏提取物和天麻蜜环粉。

银杏叶提取物后处理对兔心肌缺血-再灌注损伤的影响

目的探讨银杏叶提取物(EGb761)后处理对兔心肌缺血-再灌注损伤的保护作用。方法 32只兔随机分为假手术组(S组,开胸后仅行左冠脉套线而不阻断160 min)、缺血-再灌注组(IR组,行左冠状动脉前降支阻断40 min,再灌注120 min)、缺血后处理组(IPC组,结扎冠状动脉前降支40 min,再通30 s,结扎30 s,重复3次,再灌注120 min)和EGb761后处理组(E组,开放左冠状动脉即刻1 min内予以静脉推注EGb761 100mg/kg,再灌注120 min)。分别于左冠前降支阻断前20 min(T1)、左冠前降支阻断20 min(T2)、左冠前降支阻断40 min(T3)、心肌再灌注1h(T4)和心肌再灌注2 h(T5)抽取颈内动脉血测定血清肌钙蛋白(IcTnI)含量。再灌注末抽血离心测定超氧化物歧化酶(SOD)、丙二醛(MDA),测定梗死面积。结果和IR组相比,IPC组和E组再灌注各个时间点cTnI均降低(P<0.05);IPC组和E组梗死面积均小于IR组(P<0.05);IPC组和E组血清中SOD的活性高于IR组,MDA的含量低于IR组(P<0.05)。结论银杏叶提取物后处理具有类似缺血后处理的心肌保护作用,其机制可能是通过减少氧自由基的生成,增强心肌抗氧化能力有关。

银杏叶提取物对大鼠脑缺血再灌注氧化损伤的保护作用

目的观察银杏叶提取物(extracts of Ginkgo biloba leaf,EGB)对大鼠脑缺血再灌注氧化损伤的保护作用,为进一步开展复方候选新药筛选研究提供参考依据。方法雄性Wistar大鼠60只,随机等分为①对照组,②模型组,③假手术组,④EGB低剂量组,⑤EGB中剂量组,⑥EGB高剂量组。第①～③组灌胃给予蒸馏水l0 ml/kg,第④～⑥组分别灌胃给予含EGB 25、50、100 mg/kg的蒸馏水混悬液l0 ml/kg,连续14 d。最后一次灌胃后1h,②、④、⑤、⑥组大鼠均结扎双颈总动脉造成不完全性脑缺血1 h,复灌30 min;①组不做处理,③组仅做手术处理不结扎颈总动脉。取各组大鼠大脑皮层制备组织匀浆,检测超氧化物歧化酶(SOD)和一氧化氮合酶(NOS)活性,谷胱甘肽(GSH)和丙二醛(MDA)含量以及总抗氧化能力(T-AOC)等指标的变化。结果与对照组相比,模型组脑组织中的SOD活性、GSH含量和T-AOC显著下降,而NOS活性和MDA含量明显升高;与模型组相比,给于EGB使脑组织中SOD活性、GSH含量和T-AOC明显升高,NOS活性和MDA含量明显降低,中剂量的效果较好。结论 EGB对大鼠脑缺血再灌注氧化损伤具有明显保护作用,且呈一定的剂量相关特性。

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 10 min静脉给予生理盐水或不同剂量的 EGb 761,检测缺血再灌区心肌组织丙二醛 ( 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 ,EGb 761治疗组心肌MDA、NO含量下降 ,但下降程度与 EGb 761剂量不呈量效关系。结论 :EGb 761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。

银杏叶提取物防治心脑血管疾病的研究进展

银杏叶提取物(Ginkgo biloba extract)是目前国际上使用最为广泛的中药提取物之一,主要活性成分是银杏黄酮和银杏内酯类化合物。心脑血管疾病是全球主要的病死原因,对其防治具有重要的意义。近年来的研究表明,银杏叶提取物对心脑血管疾病的防治有多环节、多靶点、不良反应小的优势,应用前景良好。因此,本文综述了近年来银杏叶提取物对心脑血管疾病的防治作用和机制。