Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761

Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, has been used in clinical trials for its beneficial effects on brain functions, particularly in connection with age-related dementias and Alzheimer's disease (AD). Substantial experimental evidence indicates that EGb761 protects against neuronal damage from a variety of insults, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing an AD-associated double mutation, we report that EGb761 inhibits formation of amyloid-beta (Abeta) fibrils, which are the diagnostic, and possibly causative, feature of AD. The decreased Abeta fibrillogenesis in the presence of EGb761 was observed both in the conditioned medium of this Abeta-secreting cell line and in solution in vitro. In the cells, EGb761 significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of caspase 3, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that (i) neuronal damage in AD might be due to two factors: a direct Abeta toxicity and the apoptosis initiated by the mitochondria; and (ii) multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of Abeta aggregation, underlie the neuroprotective effects of EGb761.     

Ginkgo biloba extract EGb 761 and Wisconsin Ginseng delay sarcopenia in Caenorhabditis elegans

Previously we reported that the standardized Ginkgo biloba extract EGb 761 extended life span and increased stress resistance in Caenorhabditis elegans. In this study, pharmacological modulation of age-dependent muscle degeneration, or sarcopenia, was determined. Transgenic C. elegans strain (PD4251) expressing green fluorescent protein (GFP)-MYO-3, localized in body wall muscles and vulval muscle nuclei, were fed with EGb 761 or Wisconsin Ginseng, and muscle integrity was analyzed by quantification of GFP fluorescence. Both EGb 761 and Wisconsin Ginseng significantly delayed sarcopenia. Ginseng was more effective in worms of more advanced age, which is consistent with the ultrastructural changes observed by transmission electron microscopy. Furthermore, both agents ameliorated age-associated decline of locomotive behaviors including locomotion, body bend, and pharyngeal pumping. These results suggest that pharmacological extension of life span is a consequence of maintaining functional capacity of the tissue, and that C. elegans is a valid model system for testing therapeutic intervention for delaying the progress of sarcopenia.     

银杏叶提取物EGb761对铜与高胆固醇共处理家兔主动脉病变的影响

目的 观察银杏叶提取物EGb761对铜和高胆固醇诱导的家兔主动脉病变的保护作用.方法 采用Sparks的方法复制铜和高胆固醇家兔模型,EGb761以50 mg·kg-1·d-1的剂量灌胃3 w后,苏丹Ⅲ和HE染色观察主动脉的大体和镜下形态改变,图像分析测量动脉粥样硬化面积占主动脉面积的百分比,酶法检测血清总胆同醇(TC)、甘油三酯( TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,硫代巴比妥酸( TBA)法测定血清丙二醛(MDA)水平,实时定量RT-PCR法检测肝组织LDLR和LR PI mRNA表达.结果 模型组主动脉可见明显的动脉粥样硬化改变,EGb761组动脉粥样硬化病变较模型组减轻,图像分析结果显示,EGb761组斑块面积百分比显著降低,与模型组相比差别具有统计学意义(P＜0.05).模型组血清TC、TG、HDL-C、LDL-C和MDA水平均显著升高,与正常组相比差别具有统计学意义(P＜0.05);EGb761组血清LDL-C和MDA水平均显著降低,与模型组相比差别具有统计学意义(P＜0.05).EGb761组肝组织LRPI mRNA表达显著升高,与模型组相比差别具有统计学意义(P＜0.05).结论 EGb761具有改善动脉粥样硬化病变的作用,其作用机制与调节血脂水平和抗过氧化损伤有关.     

Effect of the antioxidant action of Ginkgo biloba extract (EGb 761) on aging and oxidative stress

Aging is responsible for oxidative damage to DNA, protein, lipid, and other macromolecules linked to tissue alterations. The resultant damage contributes significantly to degenerative diseases, to include those of the brain, sensorial tissues, and cardiovascular system. To protect cellular components from oxyradical attack, especially lipoperoxidation, a substantial interest in the use of antioxidants has evolved. A free radical scavenger, Ginkgo biloba extract (EGb 761) may be effective in fighting the oxidative stress related to aging. Many data support the efficacy of EGb 761 in biological model systems. In aging processes, EGb 761 may ameliorate the mitochondria respiratory chain function by quenching the superoxide anion, and the hydroxyl and peroxyl radicals. It protects the brain by facilitating the uptake of neurotransmitters and by reducing ischemia-reperfusion episodes and level of apoptosis. Moreover, in sensorial tissues, EGb 761 reduces apoptosis in the olfactive bulb and in the retinal pigmented epithelium of the eye, and protects against the lipoperoxidation alteration of the retina that results in a decrease of the electroretinogram response. In the cardiovascular system, by a direct effect on oxidative low density lipoproteins, EGb 761 may decrease atherosclerosis evolution, and is shown to accelerate cardiac mechanical recovery after ischemia-reperfusion. In conclusion, the antioxidant effects of EGb 761 noted in many experimental data, may explain the therapeutic efficacy observed in clinical trials of the elderly. These beneficial properties seem in part to come from the activity of EGb 761 constituents, such as flavonoids and terpens.     

Short-term oral ingestion of Ginkgo biloba extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects

We have recently reported that ingestion of Ginkgo biloba extract (EGb 761) (a) significantly reduced collagen-induced platelet aggregation and thromboxane B2 (TXB2) production in both non-diabetic individuals as well as those with type 2 diabetes mellitus (T2DM), (b) significantly reduced platelet malondialdehyde (MDA), an index of lipid peroxidation, in non-diabetic subjects. In the present study we report that ingestion of EGb 761 (120 mg daily for 3 months), significantly decreased platelet MDA-thiobarbituric acid reacting substances (TBARS) (41 +/- 9 pmol/10(7) platelets versus 30 +/- 11 pmol/10(7) platelets) (p < 0.005) in T2DM subjects with normal cholesterol levels (total cholesterol, 164 +/- 22 mg/dl; age, 54 +/- 9 years; BMI, 35.0 +/- 8.8 kg/m2, n = 12). In T2DM subjects with high cholesterol (total cholesterol, 218 +/- 15 mg/dl; age, 52 +/- 5 years; BMI, 36.2 +/- 6.6 kg/m2, n = 7), EGb 761 ingestion reduced the platelet TBARS from 29 +/- 9 to 22 +/- 9 pmol/10(7) platelets (p < 0.04). Because ingestion of EGb 761 did not alter platelet counts it is concluded that EGb 761, probably due to the flavonoid fraction, reduced the TBARS by inhibiting cyclooxygenase (COX)-1-mediated arachidonic acid oxygenation or by reducing the arachidonic acid pool. This is likely to lead to a reduction of platelet hyperactivity, a significant contributor to the development of cardiovascular disease in T2DM patients. Because of other reported beneficial properties of EGb 761, such as stimulation of pancreatic beta-cell function in T2DM subjects with pancreatic exhaustion, it appears that T2DM subjects might benefit from ingesting EGb 761 as a dietary supplement.     

Protective effect of the standardized leaf extract of Ginkgo biloba (EGb761) against hypertension-induced renal injury in rats

ABSTRACT

Background: Ginkgo biloba leaves extract has been widely used worldwide to protect against oxidative stress-induced cell damage and improves blood circulation. Methods: The potential protective role of the standardized leaf extract of Ginkgo biloba (EGb761) on hypertension-induced renal injury was investigated in rats. Hypertension was induced in rats by L-NAME. Result: Repeated treatment with EGb761 produced progressive reductions in the systolic, diastolic and mean arterial blood pressure. Also, EGb761 increased the progressive reductions in blood pressure induced by losartan. Hypertension-induced marked elevation of renal malondialdehyde (MDA) and nitrite levels and reduction of reduced glutathione (GSH) level were inhibited by EGb761. In addition, hypertension-induced increases in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)) levels in renal tissues were inhibited by EGb761. Also, treatment with EGb761 inhibited hypertension-induced decrease in endothelial nitric oxide synthase (eNOS) protein expression and increase in the protein expressions of inducible NO synthase (iNOS), TNF-α, IL-6 and IL-1B in the kidney tissues. EGb761 enhanced losartan effects on renal tissues oxidative stress, nitrite, and inflammatory markers levels and on protein expressions of eNOS, iNOS, TNF-α, IL-6 and IL-1B. effects. Conclusions:These results indicate that EGb761 has the ability to protect against hypertension-induced renal injury.     

Complementary cardioprotective effects of flavonoid metabolites and terpenoid constituents of Ginkgo biloba extract (EGb 761) during ischemia and reperfusion

Hemodynamic and electron spin resonance (ESR) analyses were performed on isolated ischemic and reperfused rat hearts to assess the cardioprotective and antioxidant effects of therapeutically relevant concentrations of Gingko biloba extract (EGb 761; 5, 50 or 200 μg/ml), its terpenoid constituents (ginkgolide A; 0.05 μg/ml and ginkgolide B; 0.05, 0.25 or 0.50 μg/ml), and a terpene-free fraction of EGb 761 (CP 205; 5 or 50 μg/ml). Hearts underwent 10 min of low-flow ischemia, 30 min of no-flow global ischemia, and 60 min of reperfusion. Test substances were added to the perfusion fluid during the last 10 min of control perfusion, low-flow ischemia and the first 10 min of reperfusion. A separate group of rats were treated with CP 205 (60 mg/kg/day; p.o.) for 15 days, after which the hearts were perfused with plain buffer. In ESR experiments, the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was added to the perfusate to determine the effects of treatment on post-ischemic myocardial free radical generation. Results showed that in vitro exposure of hearts to EGb 761 (5 or 50 μg/ml) or to ginkgolides A and B (both at 0.05 μg/ml), or in vivo pretreatment of the rats with CP 205 delayed the onset of contracture during ischemia. The strong reperfusion-induced elevation of left ventricular end-diastolic pressure observed in untreated hearts was significantly reduced by in vitro exposure to the lowest concentrations of EGb 761, by ginkgolide A, and to a lesser extent by ginkgolide B, or by prior oral treatment with CP 205. Post-ischemic functional recovery was significantly improved by in vivo administration of CP 205, by perfusion with 5 μg/ml of EGb 761 or with both terpenoids as compared to untreated group but in vitro CP 205 was not effective. ESR analyses revealed that DMPO-OH (the DMPO / hydroxyl radical spin-adduct) concentrations in coronary effluents were markedly decreased by all treatments, except for the lowest concentration of gingkolide B. Perfusing 5 μg/ml EGb 761 resulted in a better inhibition of baseline DMPO-OH concentration than 5 μg/ml CP 205 (−70% and −48% vs. control, respectively), indicating that both terpenoid and flavonoid constituents of EGb 761 are required to produce this effect. CP 205 was significantly more efficient in reducing DMPO-OH concentration when administered in vivo than when applied in vitro, indicating that the antioxidant effect of flavonoid metabolites (formed in vivo) is superior to that of intact flavonol glycosides (present in vitro). Collectively, these findings provide the first evidence that part of the cardioprotection afforded by EGb 761 is due to a specific action of its terpenoid constituents and that this effect involves a mechanism independent of direct free radical-scavenging. Thus, the terpenoid constituents of EGb 761 and the flavonoid metabolites that are formed after in vivo administration of the extract act in a complementary manner to protect against myocardial ischemia-reperfusion injury. Received: 30 September 1999 Returned for revision: 1 December 1999 Revision received: 14 January 2000 Accepted: 8 February 2000     

Ginkgo biloba extract （EGb 761） attenuates lung injury induced by intestinal ischemia/reperfusion in rats： Roles of oxidative stress and nitric oxide

AIM： To investigate the effect of ginkgo biloba extract （EGb 761） on lung injury induced by intestinal ischemia/ reperfusion （ Ⅱ/R）. METHODS： The rat model of Ⅱ/R injury was produced by damping the superior mesenteric artery for 60 min followed by reperfusion for 180 min. The rats were randomly allocated into sham, Ⅱ/R, and EGb ＋Ⅱ/R groups. In EGb ＋Ⅱ/R group, EGb 761 （100 mg/kg per day） was given via a gastric tube for 7 consecutive days prior to surgery. Rats in Ⅱ/R and sham groups were treated with equal volumes of the vehicle of EGb 761. Lung injury was assessed by light microscopy, wet-todry lung weight ratio （W/D） and pulmonary permeability index （PPT）. The levels of malondialdehyde （MDA） and nitrite/nitrate （NO2/NO3）, as well as the activities of superoxide dismutase （SOD） and myeloperoxidase （MPO） were examined. Western blot was used to determine the expression of inducible nitric oxide synthase （iNOS）. RESULTS： EGb 761 markedly improved mean arterial pressure and attenuated lung injury, manifested by the improvement of histological changes and significant decreases of pulmonary W/D and PPT （P 〈 0.05 or 0.01）.Moreover, EGb 761 markedly increased SOD activity, reduced MDA levels and MPO activity, and suppressed NO generation accompanied by down-regulation of iNOS expression （P 〈 0.05 or 0.01）. CONCLUSION： The results indicate that EGb 761 has a protective effect on lung injury induced by Ⅱ /R, which may be related to its antioxidant property and suppressions of neutrophil accumulation and iNOS- induced NO generation. EGb 761 seems to be an effective therapeutic agent for critically ill patients with respiratory failure related to Ⅱ/R.     

Ginkgo biloba Extract (EGb 761) Pretreatment Limits Free Radical Oxidative Stress in Patients Undergoing Coronary Bypass Surgery

A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This clinical study was designed to evaluate, in 15 patients undergoing aortic valve replacement, whether the extent of CPB- and reperfusion-induced lipid peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is reduced by orally administered EGb 761, a Ginkgo biloba extract withpotent in vitro antiradical properties. Patients received either EGb 761 (Tanakan, 320 mg/day, n = 8) or a matching placebo (n = 7) for 5 days before surgical intervention. Plasma samples were obtained from the peripheral circulation and the coronary sinus at crucial stages of the operation (i.e., before incision, during ischemia, and within the first 30 minutes post-unclamping), and up to 8 days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac release of thiobarbituric acid species (p ` 0.05), as assessed by high-performance liquid chromatography, and attenuated the early (5–10 minute) decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin resonance index of the plasma ascorbate pool (p ` 0.05). EGb 761 also significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days postoperatively). The clinical outcome of recovery of treated patients was improved, but not significantly, compared with untreated patients. Our results demonstrate the usefulness of adjuvant EGb 761 therapy in limiting oxidative stress in cardiovascular surgery and suggest the possible role of highly bioavailable terpene constituents of the drug.     

银杏叶提取物EGb761对局灶性脑缺血再灌注大鼠XIAP和Smac表达的影响

目的 探讨银杏叶提取物EGb761对局灶性脑缺血大鼠脑组织X-连锁凋亡蛋白抑制剂(X-linked inhibitor of apoptosis protein,XIAP)和Smac蛋白表达的影响.方法 40只雄性Wistar大鼠随机分为假手术组、脑缺血再灌注组、EGb761小剂量组和EGb761大剂量组,每组10只.制作大鼠大脑中动脉闭塞1.5 h再灌注24 h模型.EGb761小剂量组和EGb761大剂量绀于模型制作前1 h分别腹腔注射ECY0761 50 mg/kg和100 mg/kg.大鼠脑组织XIAP和Smac表达用免疫组化方法 检测.结果 EGb761小剂量绀和EGb761大剂量组脑组织XIAP表达分别为18.33±4.01和26.7±3.27,显著高于脑缺血再灌注绀的12.13±3.44(P均<0.01),且EGb761大剂量组高于EGb761小剂量组(P<0.01);EGb761小剂量组和EGb761大剂量组脑组织Smac表达分别为21.33±3.15和11.33±2.10,显著低于脑缺血再灌注组的28.93±4.96(P均<0.05),EGb761大剂最组显著低于EGb761小剂量组(P<0.01).结论 脑缺血再灌注可诱导XIAP和Smae表达,EGn761干预在上调XIAP表达的同时能抑制Smac蛋白表达,提高XIAP/Smac比值,可能是EGb761干预的保护机制之一.     

Gingko biloba extract EGb 761 and pentoxifylline in intermittent claudication. Secondary analysis of the clinical effectiveness]

Clinical trials on the efficacy of EGb 761 and pentoxifylline are summarized in the context of their methods and results and compared with each other. All placebo-controlled, randomized and double-blind studies with the major target objective of "pain-free walking distance" were selected. The pentoxifylline studies were adopted from a survey of the existing literature in the English language, which has been brought up to date via DIMDI research. The studies on both active substances are fraught with similar difficulties as to method, and are not different as regards their quality. The increase in walking distance is highly variable, especially in the pentoxifylline studies. On average through each and all of the studies on both preparations, an increase of 45% (EGb 761) or 57% (pentoxifylline) in relation to initial values is here found. No differences in the documentation of efficacy and the clinical efficacy were discovered between the two substances, both of which are registered as effective substances in the treatment of peripheral arterial occlusion (pAO) in accordance with the Federal German Drugs Law (Arzneimittelgesetz, AMG) of 1976.     

No alteration in the PFA-100 in vitro bleeding time induced by the Ginkgo biloba special extract, EGb 761, in elderly patients with mild cognitive impairment.

EGb 761 is widely used in the management of mild cognitive impairment in the elderly population. Elucidation of the effects of EGb 761 on primary haemostasis via PFA-100 could represent an important step for better understanding of the haemostatic safety of EGb 761. The purpose of this prospective study is to assess the effects of Ginkgo biloba special extract, EGb 761, on PFA-100 in vitro bleeding time in elderly patients with mild cognitive impairment. A total of 40 elderly patients aged 65-79 years who were referred for geriatric assessment and who were diagnosed as having mild cognitive impairment were included. Patients were started on 80 mg EGb-761 three times daily. The complete set of PFA-100 in vitro bleeding time and coagulation parameters including prothrombin time, activated partial thromboplastin time and International Normalized Ratio were assessed before and on the seventh day of treatment with EGb 761. There was no statistically significant prolongation in PFA-100 in vitro bleeding time or coagulation parameters in patients receiving EGb 761 after 7 days. The data about the safety of EGb 761 from the point of primary haemostasis in our elderly patient population with mild cognitive impairment casts hope for the future management of this 'difficult-to-treat' population with the promising Ginkgo extracts.     

Effects of Ginkgo biloba extract on cell proliferation and cytotoxicity in human hepatocellular carcinoma cells

AIM: To study the effect of Ginkgo biloba extract (EGb 761) containing 22-27% flavonoids (ginkgo-flavone glycosides) and 5-7% terpenoids (ginkgolides and bilobalides) on cell proliferation and cytotoxicity in human hepatocellular carcinoma (HCC) cells. METHODS: Human HCC cell lines (HepG2 and Hep3B) were incubated with various concentrations (0-1 000 mg/L) of EGb 761 solution. After 24 h incubation, cell proliferation and cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and lactate dehydrogenase (LDH) release, respectively. After 48 h incubation, the expression of proliferating cell nuclear antigen (PCNA) and p53 protein was measured by Western blotting. RESULTS: The results showed that EGb 761 (50-1 000 mg/L) significantly suppressed cell proliferation and increased LDH release (P<0.05) in HepG2 and Hep3B cells compared with the control group. The cell proliferation of HepG2 and Hep3B cells treated with EGb 761 (1 000 mg/L) was 45% and 39% of the control group (P<0.05), respectively. LDH release of HepG2 cells without and with EGb 761 (1 000 mg/L) treatment was 6.7% and 37.7%, respectively, and that of Hep3B cells without and with EGb 761 (1 000 mg/L) treatment was 7.2% and 40.3%, respectively. The expression of PCNA and p53 protein in HepG2 cells treated with EGb 761 (1 000 mg/L) was 85% and 174% of the control group, respectively. CONCLUSION: Ginkgo biloba extract significantly can suppress proliferation and increase cytotoxicity in HepG2 and Hep3B cells. Additionally, Ginkgo biloba extract can decrease PCNA and increase p53 expression in HepG2 cells.     

银杏叶提取物对窒息后血清诱导人近曲肾小管上皮细胞损伤的影响

目的研究银杏叶提取物（EGb）对新生儿窒息后血清攻击人近曲肾小管上皮细胞（HK-2）损伤模型的影响。方法以人近曲肾小管上皮细胞（HK-2）为研究对象,200ml／L窒息血清作为攻击因素。实验共分为两阶段,均设对照组、模型组和EGb干预组（EGb预处理24h）。第一阶段EGb干预组设立5个质量浓度亚组。观察三组细胞形态学,乳酸脱氢酶（LDH）漏出率和细胞存活（MTT法）变化。第二阶段以第一阶段选出的EGb最适质量浓度预处理细胞,观察三组NF-κB p65蛋白（免疫组化）和抑制亚基I-κBα（western blot）的变化。结果与对照组相比,模型组细胞形态发生改变,LDH漏出率增加,细胞活力降低（P〈0．05）;与模型组比较,EGb预处理组细胞形态明显得到改善,LDH漏出率降低,细胞活力增加（P〈0．05）,在5—50mg／L保护效应逐渐增加,50mg／L时保护效果最强,而〉50mg／L时保护效应反而下降。与对照组相比,模型组细胞NF-κB p65蛋白表达明显增加,I-κBα量减少（P〈0．05）;与模型组比较,EGb干预组细胞NF-κB p65蛋白表达明显减少,I-κBα量增加（P〈0．05）。结论EGb具有减轻窒息血清所致HK-2细胞损伤的作用,其作用可能与抑制窒息血清所致NF—κB激活有关。     

Influence of a 7-day treatment with Ginkgo biloba special extract EGb 761 on bleeding time and coagulation: a randomized, placebo-controlled, double-blind study in healthy volunteers.

During recent years, several case reports have been published in which the authors have voiced their suspicion of a causal relationship between hemorrhagic complications and the intake of Ginkgo biloba preparations. Therefore, a trial was conducted to investigate the influence of Ginkgo biloba special extract EGb 761 on hemostasiological parameters. Fifty healthy, male volunteers underwent 7 days of crossover treatment with 2 x 120 mg/day EGb 761 and placebo in randomized sequence. Between the two treatment phases, a washout-period of at least 3 weeks was inserted. The study's main outcome measures were bleeding time, coagulation parameters, platelet activity in response to various agonists and platelet morphology. The equivalence of the two treatments was analyzed by computing the 90% Fieller confidence intervals for the ratio between the means of the pre-post treatment differences for EGb 761 and placebo, respectively. Treatment safety was investigated by clinical laboratory and vital signs assessment and by adverse events monitoring. Among the 29 coagulation and bleeding parameters assessed, none showed any evidence of an inhibition of blood coagulation and platelet aggregation through EGb 761. Furthermore, the study did not reveal any evidence to substantiate a causal relationship between the administration of EGb 761 and hemorrhagic complications. As regards treatment tolerability, there were no interpretable differences between EGb 761 and placebo except for a slight increase of gastrointestinal complaints during administration of the herbal extract.     

High-density lipoprotein increases intracellular calcium levels by releasing calcium from internal stores in human endothelial cells

Elevated levels of high-density lipoproteins (HDL) appear to delay or prevent the development of atherosclerosis. The intracellular signaling mechanisms activated by HDL in vascular cells are currently under active investigation. In this study the effects of HDL on endothelial intracellular Ca levels (EC Ca(i)) are investigated. We show that HDL, like low density lipoproteins (LDL), increases EC Ca(i) in a dose-dependent fashion by releasing Ca from internal stores. Neither apolipoprotein A-I (apo A-I) nor apolipoprotein A-II (apo A-II) was responsible for the increase in EC Ca(i). HDL appeared to release Ca from the same internal stores as did LDL, since preincubation of EC with LDL prevented subsequent responses to HDL but not to the vasodilator ATP. In addition, preincubation of EC with pertussis toxin, an inhibitor of specific G proteins, as well as U73122, an inhibitor of phospholipase C, prevented a rise in EC Ca(i) in response to HDL. These findings suggest that HDL, like LDL, can modulate EC Ca(i) and that this occurs via a pertussis toxin-sensitive G protein-mediated pathway which involves phospholipase C.     

Effect of Ginkgo biloba (EGb 761) and aspirin on platelet aggregation and platelet function analysis among older adults at risk of cardiovascular disease: a randomized clinical trial.

Several case reports have implicated Ginkgo biloba in clinically adverse bleeding disorders. Ginkgo biloba has been reported to increase pain-free walking distance among patients with peripheral artery disease (PAD). Standard PAD therapy includes 325 mg/day aspirin. The objective of this study was to examine potential adverse effects of concomitant aspirin and Ginkgo biloba on platelet function. Ginkgo biloba (EGb 761, 300 mg/day) was compared with placebo for effects on measures of platelet aggregation among adults consuming 325 mg/day aspirin in a randomized, double-blind, placebo-controlled, parallel design trial of 4-week duration. Participants were adults, age 69 +/- 10 years, with PAD or risk factors for cardiovascular disease. Outcome measures included platelet function analysis (PFA-100 analyzer) using ADP as an agonist (n = 26 placebo; n = 29 ginkgo), and platelet aggregation using ADP, epinephrine, collagen and ristocetin as agonists (n = 21 placebo; n = 23 ginkgo). Participants kept daily logs of bleeding or bruising episodes. There were no clinically or statistically significant differences between treatment groups for any agonists, for either PFA-100 analysis or platelet aggregation. Reports of bleeding or bruising were infrequent and similar for both study groups. In conclusion, in older adults with PAD or cardiovascular disease risk, a relatively high dose of Ginkgo biloba combined with 325 mg/day daily aspirin did not have a clinically or statistically detectable impact on indices of coagulation examined over 4 weeks, compared with the effect of aspirin alone. No adverse bleeding events were observed, although the trial was limited to a small sample size.     

银杏叶提取物抗氧化和防治心脑血管疾病的作用机制研究

本文总结了银杏叶提取物 (EGb)对自由基的清除作用、对自由基引起的脑细胞凋亡的保护作用和对心肌缺血再灌注损伤的保护作用的实验结果 ,分析了EGb抗氧化和防治心脑血管疾病的机制。     

银杏叶提取物及其合剂对饲胆固醇兔动脉粥样硬化的作用

目的：研究银杏叶提取物和银杏叶提取物合剂（银杏叶提取物＋维生素Ｅ＋Ｌ－精氨酸＋牛磺酸,２：１：２：２．５）对饲胆固醇兔动脉粥样硬化的防治作用。方法采用饲１％胆固醇兔形成动脉粥样硬化为模型,观察银杏叶提取物和银杏叶提取物合剂对饲胆固醇兔胸主动脉动脉粥样硬化斑块面积百分比及对血浆丙二醛和一氧化氮含量的影响。结果银杏叶提取物合剂（１－３ｍｇ／ｋｇｐｅｒｄａｙ）和银杏叶提取物（０．５ｍｇ／ｋｇｐｅｒｄａｙ