A placebo-controlled study of extract of ginkgo biloba added to clozapine in patients with treatment-resistant schizophrenia

The focus of this study was the systematic evaluation of the clinical effects of the extract of ginkgo biloba (EGb) as an adjunct to the atypical antipsychotic clozapine in the treatment of refractory schizophrenia. In a placebo-controlled study, 42 patients with chronic, treatment-resistant schizophrenia, who were maintained on optimal doses of clozapine, were administered either 120 mg/day of EGb (N=20) or placebo (N=22) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Positive Symptoms, and the Scale for the Assessment of Negative Symptoms were completed biweekly. The use of EGb as an adjunct to clozapine was effective in decreasing negative symptoms, but not positive and overall psychopathology symptoms. EGb produced a mean 7.9+/-7.0 point reduction in the total Scale for the Assessment of Negative Symptoms score compared with a mean 1.8+/-3.5 point reduction in the placebo group (P=0.034). These preliminary data suggested that EGb was found useful for enhancing the effect of clozapine on negative symptoms in patients with treatment-resistant schizophrenia.     

The effects of Ginkgo biloba extract added to haloperidol on peripheral T cell subsets in drug-free schizophrenia: a double-blind, placebo-controlled trial

Objective To investigate the effects of Ginko biloba extract (EGb) administration on T lymphocyte subsets and superoxide dismutase (SOD) levels in schizophrenia.Methods One hundred and nine schizophrenic inpatients were randomly assigned to 12 weeks of treatment with 360 mg/day of EGb plus a stable dose of 0.25 mg kg⁻¹ day⁻¹ of haloperidol and placebo plus the same dose of haloperidol using a double-blind design. Clinical efficacy was determined using the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive Symptoms, and Scale for Assessment of Negative Symptoms. T lymphocytes (CD3+), T helper cells (CD4+), T suppressor cells (CD8+), and IL-2-secreting cells were measured using the alkaline phosphatase/antialkaline phosphatase technique; and SOD levels were measured by radioimmunometric assay at baseline and at posttreatment, as compared to 30 sex- and age-matched normal subjects.Results Patients demonstrated significantly lower CD3+, CD4+, and IL-2-secreting cells, together with CD4/CD8 ratio, and significantly higher blood SOD levels than did healthy controls at baseline. There was a significantly negative relationship between SOD and CD4+ cells in the schizophrenic group at baseline. After a 12-week treatment, CD3+, CD4+, and IL-2-secreting cells, together with CD4/CD8 ratio, showed a significant increase, but a significant decrease in SOD levels in the EGb group. There was only a significant increase in CD4+ cells but no change in SOD levels in the placebo group. There was a significant correlation between the change in CD4+ cells at posttreatment vs pretreatment and a reduction of BPRS total score in the whole patient group.Conclusions EGb may improve the decreased peripheral immune functions in schizophrenia. The beneficial effects of EGb on the immune systems and the improvement of schizophrenic symptoms may be medicated through its antioxidant activity.     

The effect of risperidone treatment on superoxide dismutase in schizophrenia

Some reports have shown that schizophrenia is accompanied by the abnormal metabolism of free radicals. The purpose of this study was to investigate the effect of the atypical antipsychotic drug risperidone on blood superoxide dismutase (SOD), a critical enzyme in the detoxification of superoxide radicals, and to explore the relationship between changes in SOD and the therapeutic outcome. Forty-one inpatients with diagnosed schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone at a fixed dosage of 6 mg/d after a 2-week washout period. Clinical efficacy was determined with the Positive and Negative Syndrome Scale (PANSS). Blood SOD was assayed by radioimmunoassay (RIA) in schizophrenic patients before and after the 12-week treatment, and the values were compared with those of 50 age-, sex-, and smoking-matched subjects without schizophrenia. Risperidone treatment significantly decreased the initially high blood SOD levels in schizophrenia. There was a significantly positive relationship between the change in SOD at pretreatment and posttreatment and the reduction in the PANSS negative subscore. These findings suggest that risperidone treatment significantly decreased the blood SOD levels of schizophrenic patients, a change which may be associated with the diminishment of symptoms. The limitations of this study are the measurement of SOD levels by RIA rather than biochemical assay; the 2-week washout, which may not be adequate; and the measurement of only SOD enzyme and not the other antioxidant enzymes.     

银杏叶提取物对老龄大鼠心肌老化的影响

目的 研究银杏叶提取物对老龄大鼠心肌老化的影响.方法 老龄雄性大鼠10只(老龄治疗组)用银杏叶提取物灌胃治疗16周;另设老龄对照组和成年对照组各10只.比较各组大鼠心肌电镜下超微结构改变、血清氧化指标超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-Px)、丙二醛(MDA)、心肌糖基化终末产物(AGEs)含量以及心肌线粒体DNA缺失率的差别.结果 老龄对照组大鼠心肌组织电镜下结构发生明显老化病理变化,间质增生,线粒体肿大,闰盘模糊.而在老龄治疗组,病理情况明显改善,与成年对照组有比较相似的超微结构.老龄治疗组大鼠血清SOD、GSH-Px与老龄对照组相比显著增多(P＜0.05),而血清MDA、心肌AGEs含量及心肌线粒体DNA缺失率显著下降(P＜0.05),且都与成年对照组无显著性差异(P＞0.05).结论 银杏叶提取物可以抑制氧化、抑制非酶糖基化,从而减缓心肌老化.     

Effects of risperidone and haloperidol on superoxide dismutase and nitric oxide in schizophrenia

Oxidative stress may be involved in the pathophysiology of schizophrenia. No double-blind study has compared the effects of typical and atypical antipsychotics on both antioxidant enzyme activity and nitric oxide (NO) levels in schizophrenic patients. Seventy-eight inpatients with chronic schizophrenia were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design. Clinical efficacy was determined using the Positive and Negative Syndrome Scale. Blood superoxide dismutase (SOD) and plasma NO levels were measured in patients and 30 normal controls. Our results showed that following a 2-week washout period, levels of SOD and NO were significantly increased in patients with schizophrenia compared to normal controls. Both risperidone and haloperidol equivalently reduced the elevated blood SOD levels in schizophrenia, but neither medication reduced the elevated plasma NO levels in schizophrenia. Low blood SOD levels at baseline predicted greater symptom improvement during treatment, and greater change in SOD was correlated with greater symptom improvement. These results suggest that both typical and atypical antipsychotic drugs may at least partially normalize abnormal free radical metabolism in schizophrenia, and some free radical parameters at baseline may predict antipsychotic responses of schizophrenic patients.     

The effect of ginkgo biloba extract on free radical production in hypoxic rats.

In the present study, we assayed the antioxidant properties of Ginkgo biloba (Gb) extract on rats submitted to 21 d of chronic hypoxia. Doses of 25 and 50 mg/kg were examined. Oxygenated free radical production measured by the chemiluminescence technique was significantly decreased in treated rats compared to control rats placed in similar experimental conditions, and this effect was more significant at the 50 mg/kg dose. On the other hand, no antioxidant enzyme activities of the drug were observed towards red blood cells. These results suggest that ginkgo biloba extract has a free radical scavenging action. These antioxidant properties could explain the beneficial hematological properties of Gb extract.     

银杏叶提取物对大鼠离体心脏缺血再灌注损伤的保护作用

氧自由基在心肌缺血再灌注损伤中扮演了很重要的角色[1]。银杏叶提取物在体外实验中可直接灭活各类氧自由基[2,3],我们实验发现银杏叶提取物可以抑制Ｈ2Ｏ2对培养大鼠心肌细胞造成的损伤。本实验利用离体心脏的灌注模型,观察了最新一代的银杏叶提取物金纳多对大鼠心肌缺血再灌注损伤的作用及其机制。1　材料与方法1.1　药品　银杏叶提取物由德国威玛舒培药厂提供,针剂,批号:Ｘ940261,其有效成分为24%黄酮类及6%萜内酯类,包括银杏内酯和白果内酯。1.2　动物　(200±50)ｇ♂大鼠,由上海医科大学实验动物中心提供。1.3　实验方法　常规方法制备…     

银杏叶提取物治疗慢性肺源性心脏病40例临床观察

目的观察银杏叶提取物辅助治疗慢性肺源性心脏病（简称肺心病）急性加重期的疗效及治疗前后血浆C反应蛋白、纤维蛋白原、D-二聚体含量的变化。方法观察40例肺心病急性加重期患者在常规治疗基础上,加用银杏提取物20ml加入5%葡萄糖注射液（或生理盐水）中静脉滴注,1次/d,14d为1个疗程。另38例以常规治疗为对照组。结果两组显效率分别为87.50%和68.42%,总有效率为97.50%和86.84%,差异有统计学意义（P〈0.05）;治疗后两组间血浆C反应蛋白含量差异有统计学意义（P〈0.01）,纤维蛋白原、D-二聚体含量差异有有统计学意义（P〈0.05）。结论银杏叶提取物可明显改善机体炎症反应,降低血黏度,提高肺心病急性加重期的临床疗效。     

Protective effect of ginkgo biloba extract on endothelial cell against damage induced by oxidative stress

The viability of bovine aortic endothelial cells (BAECs) treated with 0.1 m H O was decreased by 39.8%, and 100 mg/l EGb761 increased the viability by 20.6%. Exposure BAECs to H O for 6 min resulted in a significant elevation in the intracellular free Ca. Pretreatment of BAECs with 10 mg/l and 100 mg/l EGb761 for 10 min showed a decrease in the intracellular free Ca, 4.5% and 20.6%, respectively. The apoptotic rate of BAECs measured by propidium iodide (PI) staining was (38.1 +/- 2%) after 18 h of treatment with H O. Pretreatment of BAECs with 100 mg/l EGb761 for 1 h reduced the apoptotic rate to 27 +/- 1%. In addition, there were about 5-7% of cells stained positive measured by TUNEL assay. When BAECs were exposed to 0.1 m H O for 18 h, the number of TUNEL-positive cells increased to 37-44%. When 10 mg/l EGb761 and 100 mg/l EGb761 were used, the TUNEL-positive cells decreased to 26.5 +/- 3.1% and 17.5 +/- 1.7%, respectively. Furthermore, EGb761 also inhibited caspase-3 activity induced by H O. It is concluded that EGb761 has protective effect on bovine vascular endothelial cells against damage induced by H O. Further studies are needed to clarify the mechanisms of action of EGb761.     

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。     

银杏叶提取物对实验性高脂血症及脂质过氧化作用的影响

目的观察银杏叶提取物（GBE）对高脂血症大鼠血脂代谢及脂质过氧化反应的影响。方法高脂乳剂灌胃30d,同时给大鼠灌胃GBE（40,80,160mg·kg^-1）,测定血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL—C）、高密度脂蛋白（HDL-C）的活性,测定血清一氧化氮（NO）、丙二醛（MDA）及超氧化物歧化酶（SOD）活性。结果GBE（80,160mg·kg^-1）组均能明显降低血清TC、TG、LDL—C及MDA的活性（P〈0．05或P〈0．01）,并能显著升高血清HDL—C和NO、SOD的活性（P〈0．05或P〈0．01）。结论GBE能通过调节脂蛋白-胆固醇代谢,改善血管内皮功能、纠正自由基代谢紊乱、促进抗氧化酶活性等途径发挥调脂及抗氧化作用。     

银杏叶提取物对神经系统损伤的保护作用

银杏叶提取物(EGb761)是一种具有多种生物活性的中药制剂,研究表明EGBb761中的黄酮类单体皆有高效的抗自由基的作用,内酯部分在保护细胞免受损伤等方面也起重要作用,该文就EGb761对神经系统损伤保护作用作一综述.     

银杏叶提取物治疗顺铂所致大鼠肾损伤

目的研究银杏叶提取物(EGb)对顺铂所致肾损伤的保护作用及其作用机制.方法单次腹腔注射顺铂(7.5 mg·kg-1)于大鼠体内,建立肾损伤模型.连续5 d用EGb(50 mg·kg-1或100 mg·kg-1)灌胃大鼠一次.结果单次腹腔注射顺铂可诱导大鼠肾功能损伤,促进血清肌酐(Cr)和尿素氮(BUN)水平上升和肾皮质丙二醛(MDA)含量增加;同时抑制对氧磷酶(PON1)和超氧化物歧化酶(SOD)活性.EGb可显著性降低顺铂所致血清Cr、BUN和肾皮质MDA含量升高,抑制PON1和SOD活性下降,并减轻肾组织的病理学损伤.结论EGb对顺铂所致肾功能损伤有明显保护作用,其作用机制可能与抗氧自由基损伤,增加对氧磷酶活性有关.     

海昆肾喜胶囊联合银杏达莫注射液治疗慢性肾衰竭的临床观察

目的观察海昆肾喜胶囊联合银杏达莫注射液治疗慢性肾衰竭的临床疗效。方法将42例慢性肾衰竭患者随机分为观察组与对照组,各21例,两组均给予低盐、低脂、优质低蛋白饮食等基础治疗,对照组给予海昆肾喜胶囊口服,观察组在对照组基础上加用银杏达莫注射液,疗程3个月,比较两组疗效及治疗前后血肌酐、血尿素氮、24 h尿蛋白定量。结果观察组总有效率高于对照组,差异有统计学意义(P<0.05)。观察组治疗后血肌酐、血尿素氮及24 h尿蛋白定量明显低于对照组,差异有统计学意义(P<0.05)。结论海昆肾喜胶囊联合银杏达莫注射液可明显改善慢性肾衰竭患者的肾功能,延缓肾衰竭进展。     

银杏达莫注射液治疗120例原发性肾病综合征临床疗效分析

目的评价银杏达莫注射液对原发性肾病综合征的临床治疗效果。方法将238例原发性肾病综合征患者随机分成2组,对照组118例,实施常规疗法,给予1 mg/（kg.d）强的松及其他对症治疗。治疗组120例,在常规治疗前提下,给予银杏达莫注射液治疗。结果治疗后,治疗组PT、APTT、Fbg、HCT及D-二聚体明显改善（P〈0.05）;对照组治疗前、治疗后比较,差异无统计学意义（P〉0.05）;两组各指标比较,差异有统计学意义（P〈0.05）。治疗后,两组尿蛋白、血浆蛋白、胆固醇、甘油三酯均明显改善（P〈0.05）;两组各指标比较,差异有统计学意义（P〈0.05）。结论银杏达莫注射液能够有效改善肾病综合征的高凝状态,降低尿蛋白,增加血浆清蛋白浓度,控制脂质代谢,加快肾病综合征的缓解。     

Antagonistic effects of extract from leaves of ginkgo biloba on glutamate neurotoxicity.

AIM: To determine whether the extract of leaves of Ginkgo biloba L (EGb) and several active constituents of EGb have protective effects against glutamate (Glu)-induced neuronal damage. METHODS: Microscopy and image analysis of nucleus areas in the arcuate nuclei (AN) of mice were made. The neuronal viability in primary cultures from mouse cerebral cortex was assessed using MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] staining and the intracellular free calcium concentration ([Ca2+]i) of single neuron was measured using Fura-2. RESULTS: EGb (2.5 mg.L-1) and its constituent ginkgolide B (Gin B, 2 mg.L-1) protected the neuronal viability against Glu-induced injury, and prevented the Glu-induced elevation in [Ca2+]i. EGb (3-10 mg.kg-1) attenuated the decrease of nucleus areas in arcuate nuclei induced by Glu (1 g.kg-1, s.c.). CONCLUSION: EGb and Gin B prevent neurons from Glu neurotoxicity through reduction of the rise in [Ca2+]i.     

银杏叶注射液治疗不稳定心绞痛

目的　评价银杏叶注射液治疗不稳定心绞痛 (UAP)的临床疗效。方法　将 72例UAP病人随机分为治疗组、对照组各 36例 ,均服用抗心肌缺血基础药物 ,治疗组加用银杏叶注射液 10ml静滴 ,每天 1次 ,连用 14d。对照组口服阿司匹林 10 0mg ,每天 1次。结果　总有效率治疗组 91 6 7% ,对照组 6 9 4 4 % (P<0 0 5 ) ;治疗组全血粘度、血浆粘度、全血还原粘度、血小板聚集率均显著降低 (P <0 0 1) ,明显低于对照组(P <0 0 5 )。结论　在常规治疗的基础上联合银杏叶注射液治疗不稳定心绞痛效果显著 ,不良反应少。     

The effect of liposomes with superoxide dismutase on A2182 cells.

Differently charged liposomes were examined for the efficiency of delivery of Cu/Zn superoxide dismutase (CuZnSOD) to human lung epithelial cells, A2182, and their prospects of cell protection from oxidative agents. A2182 cells were treated with cationic, neutral and anionic liposomes with encapsulated CuZnSOD. Untreated cells and cells pre-treated with liposome-encapsulated CuZnSOD were exposed to oxidative stress caused by xanthine/xanthine oxidase. Cellular antioxidant response was monitored for 4 or 24h after the beginning of oxidative stress induced by the activity of superoxide dismutase (SOD) and total glutathione concentration. CuZnSOD-loaded liposomes increased the SOD activity of A2182 cells 24h after treatment. The highest increase of cellular SOD, by 108%, was achieved using anionic liposomes. Neutral and cationic liposomes increased cellular SOD by 83 and 85%, respectively. Cationic liposomes were the most cytotoxic. Exposure of untreated cells to oxidative stress increased the cellular glutathione level after 24h. Cells pre-treated with liposome-encapsulated CuZnSOD were protected from oxidative stress, as shown by the unchanged concentration of cellular glutathione.