银杏叶提取物的研究进展--天然药化学习资料

1、银杏叶提取物的研究进展-天然药化Click to add Title1Click to add Title2Click to add Title3Click to add Title4 Add your text in here Add your text in here Add your text in here Add your text in here Add your text in here Click to add Text Click to add Text Click to add Text Click to add Text Click to add TextContents

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15、n Digital Content & Contents mall developed by Guild Design Inc.TitleTitleTitleTitleTitleTitleDiagramTitleTitle Add your text in here - Your text in here - Your text in here Add your text in here - Your text in here - Your text in here Add your text in here Add your text in here - Your text in h

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18、our text in here Add your text in here Add your text in hereDiagram1996年Add your text in here- Your text in here- Your text in here银杏叶研究开发近况银杏叶研究开发近况.2O世纪60年代初600年前 德国德国Willamar Schwabe首次从银杏叶中获首次从银杏叶中获得银杏提取物得银杏提取物(EGB716),用于治疗用于治疗心脑血管疾病和神心脑血管疾病和神经系统疾病，具有经系统疾病，具有显著的疗效且无明显著的疗效且无明显的毒副作用显的毒副作用 银杏提取物银杏提取

19、物(GBE)成成为欧洲最畅销的保为欧洲最畅销的保健品，在美国也是健品，在美国也是最受欢迎的五种保最受欢迎的五种保健品之一，银杏制健品之一，银杏制剂年销售额已经突剂年销售额已经突破破1O亿美元亿美元银杏叶活性成分的提取分离银杏叶活性成分的提取分离超临界流体萃取法超临界流体萃取法(SFE)水浸提取法水浸提取法有机溶剂提取法有机溶剂提取法银杏叶提取物的药理作用银杏叶提取物的药理作用药药理作用理作用心血管系统的药理作用心血管系统的药理作用对心脏的保护作用对心脏的保护作用抗血栓与抗凝作用抗血栓与抗凝作用对血管的保护作用对血管的保护作用降压作用降压作用调节血脂的作用调节血脂的作用心脏的保护作用心脏的保护作

20、用v 对心脏的保护作用有研究发现EGB能显著减少离体大鼠心脏再灌注所致的心律失常，可明显降低室早的发生次数，减少室速、室颤的持续时间，降低心律失常分级，故认为EGB对心肌缺血再灌注损伤有保护作用 。v 另有实验采用结扎家兔冠状动脉前降支造成急性心肌梗死的病理模型，以心电图、血清磷酸肌酸激酶活性和梗死面积等指标评价银杏叶总黄酮对心肌缺血的保护作用，结果发现银杏叶总黄酮可明显降低心肌梗死兔EKG中sT段异常抬高的总幅度以及病理性Q波的出现次数，显著抑制心肌组织磷酸肌酸激酶释放 。抗血栓与抗凝作用抗血栓与抗凝作用v EGB能改善血液流变学，EGB静脉注射或口服可以部分拮抗电刺激动脉壁或乳酸钠对家兔软

21、脑膜所致的血小板血栓形成。v 总黄酮灌胃亦能对抗静脉注射胶原一肾上腺素所致的小鼠体内血栓形成。v 异白果双黄酮静脉注射能抑制大鼠血栓形成，减少血小板黏附，抑制兔血小板聚集 。EGB有抑制大鼠电刺激颈总动脉的血栓形成作用，且其对抗血栓形成强度具剂量依赖性 。EGB可明显延长大鼠的复钙时间，降低血液的最大粘、弹性，可明显延长血液凝固时间，对血液纤维网的形成以及血凝块的退缩均有明显抑制作用。v 体外能抑制高低浓度ADP诱导的血小板聚集 。血管的保护作用血管的保护作用v EGB通过肾上腺索能系统增强生理性血管调节，使离体动脉条呈剂量依赖性收缩，EGB能降低毛细血管的通透性，对由毛细血管通透性增加引起的

22、水肿和由单克隆丙种球蛋白引起的低血容量性休克，有较好的治疗作用。v LPC(溶血卵磷脂胆碱)可致培养血管内皮细胞损伤，而EGB可对抗LPC所造成的血管内皮细胞损伤，可能是通过清除氧自由基，抗脂质过氧化作用和提高EC产生抗氧化能力。降压作用降压作用v 银杏叶总黄酮的乙醇提取液给大鼠静脉注入，以颈动脉插管法分别观测正常麻醉大鼠、肾性高血压大鼠及自发性高血压大鼠的血压变化，并选取临床轻度、中度、重度妊娠高血压患者，每天早晚各口服银杏叶提取物。观察其用药前后尿蛋白、血压、NO含量及内皮素(ET)活性变化。结果发现，银杏总黄酮对各种高血压大鼠均有明显降压作用；并使妊娠高血压患者的尿蛋白减少，NO含量及E

23、T活性降低。大脑及神经系统的药理作用大脑及神经系统的药理作用抗痴呆(阿尔茨海默病。AD)抗癫痫抗震颤麻痹(帕金森病，PD)神经保护作用促智作用对脑缺血损伤的保护作用大脑及神经大脑及神经系统的药理作用系统的药理作用抗癫痫抗癫痫v EGB具有一定的抗癫痫作用，可作为治疗癫痫病的辅助药物。虽然临床上已证实EGB是一种理想的治疗癫痫病的辅助药，但理论研究还不十分深入，应进一步探讨其机制。神经保护作用神经保护作用v EGB可经抑制缺氧复氧时nNOS和iNOS的活性、降低NO的产生而达到其神经保护的作用。EGB有效成分复杂，神经保护作用机制仍不十分清楚，但越来越多的研究观察到 其主要作用机制之一为对氧自由

24、基强有力的清除作用 。促智作用促智作用v EGB能明显改善动物学习、记忆功能。实验以氢化可的松或环磷酰胺诱导小鼠免疫功能低下和学习记忆障碍模型。跳台法作行为检测，单向免疫扩散法和二硝基氟苯诱导迟发型超敏反应法测定有关指标，结果EGB可减少小鼠的跳台错误次数，延长其Step down latency (SDL)，缩短Escape latency(EL)，对化学物质诱导的免疫功能低下有明显的增强作用 。EGB能明显增加正常老龄前期小鼠的学习、记忆能力，且对东莨菪碱、亚硝酸钠造成的记忆缺失有不同程度的改善作用。EGB能改善动物学习、记忆障碍等功能，与其对动物隔区胆碱能神经元的保护作用有关。v EGB

25、对NO供体硝普钠(SNP)引起的大鼠海马神经元凋亡的影响，结果发现不同剂量EGB预处理海马神经元6h可剂量依赖性对抗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状改变。表明EGB对SN诱导的海马神经元凋亡也具有显著的对抗作用。抗痴呆抗痴呆(阿尔茨海默病。阿尔茨海默病。AD)v EGB可用于防治痴呆症。以B淀粉样蛋Et25 35片段(B AP25 35)诱发原代培养小鼠皮层神经元出现凋亡作为AD的离体模型，在此基础上观察了EGB对上述神经元损伤的对抗作用，表明EGB能抑制B AP25 35引起的神经元活性的下降和超微结构的改变

26、，即抑制B AP25 35诱导的神经元凋亡，是EGB临床用于防治AD的理论依据之一。v 研究了EGB对AD和多发性梗塞性痴呆(MID)的疗效，设计一项为期52周的随机、双盲、安慰剂对照、平行分组的多中心对照试验，结果表明EGB能明显改善患者的认知和社会功能。是治疗AD较理想的药物之一。抗震颤麻痹（帕金森病，抗震颤麻痹（帕金森病，PD）v EGB能有效防止帕金森病大鼠黑质细胞损伤，具有防治帕金森病的作用。v 实验证明EGB、银杏苦内酯在预防给药14d后能明显缩短急性震颤模型A的震颤时间，能减轻慢性旋转模型B的旋转行为；而且银杏苦内酯还能使模型B受损侧纹状体的多巴胺含量升高。v 实验研究，认为EG

27、B可减轻左旋多巴的神经毒性作用；并认为EGB、左旋多巴联合用于帕金森病的疗效优于单用左旋多巴。脑缺血损伤的保护作用脑缺血损伤的保护作用v EGB可明显延长双侧颈总动脉结扎导致的急性脑缺血小鼠的存活时间，显著降低小鼠脑缺血再灌期脑组织谷胱甘肽过氧化物酶和钠一钾一ATP酶活性的抑制。v 预防或治疗性静脉注射EGB均能显著减少脑缺血面积，明显改善大鼠脑缺血造成的行为障碍。EGB可促进缺血皮层脑电图(EEG)较快恢复，10 min恢复为正常的93 ，EGB对急性实验性脑缺血引起EEG改变和缺血缺氧有明显保护作用 。v 给急性不完全脑缺血模型的大鼠舌下静脉注入EGB，25 h后计算各组脑梗死体积，结果发

28、现各浓度EGB药物组的脑梗死体积明显低于对照组。该实验还发现脑局部缺血后，超氧化物岐化酶(SOD)活性明显降低而脂质过氧化物丙二醛(MDA)含量明显升高，应用EGB后能提高SOD活性，并可明显降低MDA的含量。降低缺血脑组织的含水量及其毛细血管的通透性。清除自由基和抗脂质过氧化作用清除自由基和抗脂质过氧化作用v 氧自由基反应和脂质过氧化反应在机体新陈代谢过程中起着重要作用，如果机体内自由基产生和清除的动态平衡严重失调，就会引发一系列的自由基链锁反应，导致新陈代谢失常和免疫功能降低，从而诱发疾病。v 银杏叶提取物有提高超氧化物歧化酶(SOD)活性及抗自由基作用，对诱发的脂质过氧化反应有抑制作用，

29、且作用强度随EGB浓度增加而增加r2 ，这表明EGB可通过清除自由基起到防治疾病和抗衰老的作用。胃黏膜的保护作用胃黏膜的保护作用大鼠束缚冷冻应激模型大鼠束缚冷冻应激模型小鼠无水乙醇损伤模型小鼠无水乙醇损伤模型观察观察EGB对胃黏膜损伤指数的影响对胃黏膜损伤指数的影响 幽门结扎法收集胃液幽门结扎法收集胃液 观察观察EGB对胃液分泌对胃液分泌量胃液酸度和胃蛋白酶活性的影响量胃液酸度和胃蛋白酶活性的影响采用硫代巴比妥酸采用硫代巴比妥酸(TBA)法测定法测定胃黏膜及血清中丙二醛胃黏膜及血清中丙二醛(MDA)含量含量结果表明：结果表明：EGB可剂量依赖性地可剂量依赖性地抑制束缚冷冻应抑制束缚冷冻应激和无水乙醇引激和无水乙醇引起的胃黏膜损伤起的胃黏膜损伤。EGB还能增强还能