CN116687907A - 淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用 - Google Patents
淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用 Download PDFInfo
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Abstract
本发明公开了淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，本发明利用在果蝇中表达Aβarc(北极突变体Aβ42)构建AD模型来探索淫羊藿素作为AD治疗药物的可能性。本申请证实植物天然小分子药物淫羊藿素具有显著提升Aβarc果蝇攀爬能力、飞行能力和极大延长Aβarc果蝇寿命的能力。进一步研究发现，淫羊藿素显著抑制了Aβarc果蝇大脑氧化应激状态，挽救了Aβarc果蝇大脑受损的能量代谢，极大提高了Aβarc果蝇大脑能量(ATP)的供应。更进一步研究发现，淫羊藿素几乎完全恢复了Aβarc果蝇受损的线粒体结构和功能，是保障Aβarc果蝇大脑能量供应和抑制其氧化应激的关键因素。
Description
【技术领域】
本发明属于医药用途技术领域，涉及淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用。
【背景技术】
阿尔茨海默病(Alzheimer’s disease，AD)是一种最为常见的神经退行性疾病，在老年性痴呆(Dementia)中比例高达60-80％。该病也是一种进行性发展的致死性神经退行性疾病，多起病于老年期，潜隐起病，病程缓慢且不可逆。AD在临床上主要表现为学习记忆能力下降，认知障碍，性格和行为异常，最终可导致自理能力的丧失。在病理改变上主要为双侧大脑皮质弥漫性萎缩，脑沟增宽，脑室扩大；在细胞病理学水平，主要表现为广泛的神经元丢失及两个重要的病理特点：老年斑(senile plaque，SP)和神经元纤维缠结(neurofibrillary tangles，NFT)。SP又称为淀粉样斑块，是一种胞外蛋白沉积，生物化学的研究发现其主要成分为包含40及42个氨基酸的多肽即Aβ40和Aβ42。NFT则存在于细胞内，其主要成分为高度磷酸化的微管蛋白tau。自1906年德国科学家Alois Alzheimer首次对该病进行了病理特征上的描述，对于该病的认识及研究已持续了一百多年，直至今日对于其发病机制已产生了多种看法学说，然而近20年来，占主导地位的学说仍然是Aβ级联学说，即淀粉样蛋白级联假说。
随着当今全球老龄化问题的加剧，AD病人的数目也必然随之剧增，这必将成为-个巨大的社会负担，而目前针对阿茨海默病治疗药物的开发还没有取得突破，因此开发AD的治疗药物日渐迫切。最新和最主流的“淀粉样蛋白级联假说”表明，AD的主要病理变化，包括氧化应激、能量代谢损伤、突触损伤、胶质细胞活化、炎症、Tau蛋白过度磷酸化等，都与可溶性Aβ的积累密切相关。因此，开发针对Aβ积累的治疗药物是治疗AD的关键。
由于果蝇体积小、易于繁殖和易于遗传操作，因此被广泛用于建立AD模型。果蝇AD模型几乎是通过表达人Aβ、APP、早老素和BACE生成的。这些AD模型表现出类似AD的病理和行为变化。北极突变体Aβ42(E22G)是Aβ42在家族性阿尔茨海默病(FAD)中的一个重要突变。在果蝇中，Aβarc(北极突变体Aβ42)的表达比Aβ40和Aβ42的表达更具有神经毒性，也就是说，表达Aβarc的果蝇是探索AD治疗药物的优秀果蝇AD模型。作为AD模型的Aβarc果蝇的攀爬能力、飞行能力下降和寿命缩短是其典型的表征。
目前，AD的治疗尚无特效药，对于AD的药物研究一直是热点，寻找经济有效的治疗AD的药物迫在眉睫。鉴于丰富的资源和低廉的成本，植物天然药物及其小分子提取物在AD药物开发上具有独特的优势。
淫羊藿为小檗科植物淫羊藿、箭叶淫羊藿、粗毛淫羊藿、巫山淫羊藿或朝鲜淫羊藿的干燥地上部分。中医认为其味辛、甘，性温，归肝、肾经，主治功能：补肾阳，强筋骨，祛风湿。淫羊藿含多种黄酮类成分，如淫羊藿甘、淫羊藿次苷、淫羊藿素(Icaritin，ICT)等。淫羊藿素是淫羊藿属植物提取物淫羊藿苷的水解衍生产物，属于黄酮醇类化合物，其化学结构式如下：
目前有关淫羊藿素的药理活性研究报道较少。有报道淫羊藿素可抑制体外培养的小鼠T淋巴瘤EL-4细胞的增殖并诱导其凋亡，范双翼、余英豪，中国比较医学杂志2011年21卷06期。淫羊藿素能够诱导雌激素受体阴性肿瘤细胞凋亡和生长抑制，2009年第二军医大学硕士学位论文，张妤；导师：殷正丰、吴孟超。淫羊藿素能以浓度依赖性方式有效地抑制CML原代细胞增殖和诱导CML原代细胞凋亡，2009年中南大学博士学位论文，朱剑锋；导师：张广森。中国专利CN1869204A公开了淫羊藿素在诱导干细胞体外定向分化方面的用途。中国专利CN1194701C公开了淫羊藿素或去甲淫羊藿素在制备雌激素受体调节剂的应用。
AD是一种最为常见的神经退行性疾病。近年来，研究者对AD疾病病理生理学的探索逐渐深入，但在治疗药物方面仍未取得突破。Aβ的积累在AD的发生过程中起核心作用，因此抗Aβ是治疗AD的关键。
【发明内容】
针对现有技术中治疗阿尔茨海默病尚无特效药的问题，本发明提供了淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，本发明使用实验手段考察了淫羊藿素对Aβarc诱导AD疾病的保护作用，采用Aβarc诱导果蝇AD疾病，利用淫羊藿素干预，探讨淫羊藿素对AD疾病的保护作用，为AD疾病的治疗提供新的线索。
本发明的目的通过以下技术方案来实现：
淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用。
进一步的，所述的淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，所述药物组合物是以淫羊藿素为主要成分，加上药学中可接受的辅料或辅助性成分制备成临床上可接受的药物制剂。
进一步的，所述的淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，所述药物制剂包括口服制剂和注射制剂两种剂型。
进一步的，所述的淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，所述口服制剂为口服胶囊，所述注射制剂为静脉注射液。
通常而言，作为药物，均是在制备成制剂后才临床应用。本发明所述的药物组合物，作为药物组合物可根据本领域公知的方法制备。可通过将本发明药物组合物与一种或多种药学上可接受的固体或液体赋形剂和/或辅剂结合，制成适于人或动物使用的任何剂型。本发明所述的淫羊藿素在其药物组合物中的含量通常为0.01-95％(w/w)。
本发明药物组合物或含有它的药物组合物可以单位剂量形式给药，给药途径可为肠道或非肠道，如口服、静脉注射、肌肉注射、皮下注射、鼻腔、口腔粘膜、眼、肺和呼吸道、皮肤、阴道、直肠等。
给药剂型可以是液体剂型、固体剂型或半固体剂型。液体剂型可以是溶液剂(包括真溶液和胶体溶液)、乳剂(包括o/w型、w/o型和复乳)、混悬剂、注射剂(包括水针剂、粉针剂和输液)、滴眼剂、滴鼻剂、洗剂和搽剂等；固体剂型可以是片剂(包括普通片、肠溶片、含片、分散片、咀嚼片、泡腾片、口腔崩解片)、胶囊剂(包括硬胶囊、软胶囊、肠溶胶囊)、颗粒剂、散剂、微丸、滴丸、栓剂、膜剂、贴片、气(粉)雾剂、喷雾剂等；半固体剂型可以是软膏剂、凝胶剂、糊剂等。
本发明药物组合物可以制成普通制剂、也可以制成缓释制剂、控释制剂、靶向制剂及各种微粒给药系统。为了将本发明药物组合物制成片剂，可以广泛使用本领域公知的各种赋形剂，包括稀释剂、黏合剂、润湿剂、崩解剂、润滑剂、助流剂。稀释剂可以是淀粉、糊精、蔗糖、葡萄糖、乳糖、甘露醇、山梨醇、木糖醇、微晶纤维素、硫酸钙、磷酸氢钙、碳酸钙等；润湿剂可以是水、乙醇、异丙醇等；黏合剂可以是淀粉浆、糊精、糖浆、蜂蜜、葡萄糖溶液、微晶纤维素、阿拉伯胶浆、明胶浆、羧甲基纤维素钠、甲基纤维素、羟丙基甲基纤维素、乙基纤维素、丙烯酸树脂、卡波姆、聚乙烯吡咯烷酮、聚乙二醇等；崩解剂可以是干淀粉、微晶纤维素、低取代羟丙基纤维素、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠、羧甲基淀粉钠、碳酸氢钠与枸橼酸、聚氧乙烯山梨糖醇脂肪酸酯、十二烷基磺酸钠等；润滑剂和助流剂可以是滑石粉、二氧化硅、硬脂酸盐、酒石酸、液体石蜡、聚乙二醇等。
还可以将片剂进一步制成包衣片，例如糖包衣片、薄膜包衣片、肠溶包衣片，或双层片和多层片。
为了将给药单元制成胶囊剂，可以将有效成分本发明药物组合物与稀释剂、助流剂混合，将混合物直接置于硬胶囊或软胶囊中。也可将有效成分本发明药物组合物先与稀释剂、黏合剂、崩解剂制成颗粒或微丸，再置于硬胶囊或软胶囊中。用于制备本发明药物组合物片剂的各稀释剂、黏合剂、润湿剂、崩解剂、助流剂品种也可用于制备本发明药物组合物的胶囊剂。
为将本发明药物组合物制成注射剂，可以用水、乙醇、异丙醇、丙二醇或它们的混合物作溶剂并加入适量本领域常用的增溶剂、助溶剂、pH调剂剂、渗透压调节剂。增溶剂或助溶剂可以是泊洛沙姆、卵磷脂、羟丙基-β-环糊精等；pH调剂剂可以是磷酸盐、醋酸盐、盐酸、氢氧化钠等；渗透压调节剂可以是氯化钠、甘露醇、葡萄糖、磷酸盐、醋酸盐等。如制备冻干粉针剂，还可加入甘露醇、葡萄糖等作为支撑剂。
此外，如需要，也可以向药物制剂中添加着色剂、防腐剂、香料、矫味剂或其他添加剂。
和现有技术相比，本发明具有如下优点：
1、本发明所述的淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，本申请利用在果蝇中表达Aβarc构建AD模型来探索淫羊藿素作为AD治疗药物的可能性。本申请证实植物天然小分子药物淫羊藿素具有显著提升Aβarc果蝇攀爬能力、飞行能力和极大延长Aβarc果蝇寿命的能力。进一步研究发现，淫羊藿素显著抑制了Aβarc果蝇大脑氧化应激状态，挽救了Aβarc果蝇大脑受损的能量代谢，极大提高了Aβarc果蝇大脑能量(ATP)的供应。更进一步研究发现，淫羊藿素几乎完全恢复了Aβarc果蝇受损的线粒体结构和功能，是保障Aβarc果蝇大脑能量供应和抑制其氧化应激的关键因素。
2、本发明所述的淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，基于淫羊藿素以上新性质，本发明确定了利用其制备由Aβarc诱导AD疾病保护药物的新用途，其疗效好，具有良好的前景价值。
【附图说明】
图1是本发明实验例中淫羊藿素对Aβ诱导阿尔兹海默病果蝇寿命的影响的图；
图2是本发明实验例中淫羊藿素对Aβ诱导阿尔兹海默病果蝇攀爬能力的影响的图(**P<0.01表示差异极显著，NS表示差异无明显变化)；
图3是本发明实验例中淫羊藿素对Aβ诱导阿尔兹海默病果蝇飞行能力的影响的图(**P<0.01表示差异极显著，*P<0.05表示差异显著，NS表示差异无明显变化)；
图4是本发明实验例中淫羊藿素对Aβ诱导阿尔兹海默病果蝇大脑ROS含量的影响的图(**P<0.01表示差异极显著，NS表示差异无明显变化)；
图5是本发明实验例中淫羊藿素对Aβ诱导阿尔兹海默病果蝇大脑SOD活性的影响的图(**P<0.01表示差异极显著，*P<0.05表示差异显著，NS表示差异无明显变化)；
图6是本发明实验例中淫羊藿素对Aβ诱导阿尔兹海默病果蝇大脑ATP含量的影响的图(**P<0.01表示差异极显著)；
图7是本发明实验例中淫羊藿素对Aβ诱导阿尔兹海默病果蝇受损线粒体结构的影响的图(其中：图7(a)WT组；图7(b)AD组；图7(c)ICT组；图中虚线标注的是每组果蝇的线粒体的情况，可以直观的看到：Aβ诱导阿尔兹海默病果蝇线粒体结构破损严重，淫羊藿素治疗后Aβ诱导阿尔兹海默病果蝇受损线粒体结构得到很好的修复；
图8是本发明实验例中淫羊藿素对Aβ诱导阿尔兹海默病果蝇线粒体呼吸链ComplexⅠ呼吸功能的影响的图(**P<0.01表示差异极显著，NS表示差异无明显变化)。
【具体实施方式】
以下结合实施例对本发明的具体实施方式做进一步说明。
实施例1：
淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用：
按照现有的工艺要求，制备成硬胶囊。
实施例2：
淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用：
按照现有的工艺要求，制备成注射剂。
实验例：
1、淫羊藿素治疗淀粉样蛋白Aβ诱导阿尔兹海默病果蝇模型培养条件及分组情况
成年果蝇在标准培养基上培养：ddH2O 0.65L/L，面包酵母15g/L，玉米粉38.85g/L，琼脂5.6g/L，蔗糖15.81g/L，葡萄糖31.6g/L，对羟基苯甲酸甲酯0.75g/L，并在25℃、相对湿度50％-70％的条件下进入12h/12h的光/暗循环培养。野生型W1118果蝇用作对照(Wildtype group，WT组)，表达北极突变体Aβ42的阿尔兹海默病果蝇为疾病组(Alzheimer’sdisease group，AD组)，用在食物中添加终浓度为30μM的淫羊藿素(Icaritin，ICT)喂养表达北极突变体Aβ42的阿尔兹海默病果蝇为治疗组(ICT组)。淫羊藿素喂养从果蝇羽化后开始，持续喂养25天后进行下述相关实验。
2、淫羊藿素极大延长Aβ诱导阿尔兹海默病果蝇寿命
按上述方式，实验共分为三组，分别为：野生型果蝇-WT组、阿尔兹海默病果蝇-AD组和淫羊藿素治疗阿尔兹海默病果蝇-ICT组。每组200只蝇均等装入10个装有标准食物的小瓶中，29℃培养。每隔三天将果蝇转移到装有新鲜食物的小瓶中，同时统计死亡果蝇的数量。采用GraphPad Prism软件分析果蝇存活数量。
实验结果发现：在果蝇寿命实验开始30天以内，WT组的果蝇存活数量多于ICT组，ICT组的果蝇存活数量多于AD组；在果蝇寿命实验开始30天及以后，ICT组的果蝇存活数量多于WT组和AD组(图1)。
图1淫羊藿素对Aβ诱导阿尔兹海默病果蝇寿命的影响；
实验结果说明：淫羊藿素能够极大延长Aβ诱导阿尔兹海默病果蝇寿命。
3、淫羊藿素显著提升Aβ诱导阿尔兹海默病果蝇攀爬能力
按上述方式，实验共分为三组，分别为：野生型果蝇-WT组、阿尔兹海默病果蝇-AD组和淫羊藿素治疗阿尔兹海默病果蝇-ICT组。将每组含有30只的成年果蝇分别放入直径2.1厘米、高度19.0厘米的透明测试瓶，并轻敲其到底部。由于负趋地性，果蝇可以在测试瓶壁上向上攀爬，并使用安装在测试瓶前50厘米的三脚架上的数字录像机记录果蝇的攀爬过程。在间隔60秒的3-5次连续实验中对果蝇攀爬能力进行评估。通过软件“RflyDetection”测量录像40秒时，每个测试瓶中每只苍蝇的高度，以评估果蝇的攀爬能力。所有行为记录均在25℃下进行。
实验结果发现：WT组的果蝇爬行高度与ICT组无明显差异，WT组与ICT组的果蝇爬行高度明显高于AD组(图2)。
图2淫羊藿素对Aβ诱导阿尔兹海默病果蝇攀爬能力的影响(**P<0.01表示差异极显著，NS表示差异无明显变化)。
实验结果说明：淫羊藿素显著提升Aβ诱导阿尔兹海默病果蝇攀爬能力。
4、淫羊藿素显著提升Aβ诱导阿尔兹海默病果蝇飞行能力
按上述方式，实验共分为三组，分别为：野生型果蝇-WT组、阿尔兹海默病果蝇-AD组和淫羊藿素治疗阿尔兹海默病果蝇-ICT组。将单个果蝇敲入内径为10厘米、长度为39厘米的玻璃圆柱体中，该圆柱体被分为13个区域，每个区域3厘米。记录果蝇降落的区域，并用于估计降落高度。每组使用30只苍蝇。所有行为记录均在25℃下进行。
实验结果发现：WT组的果蝇降落高度高于ICT组，ICT组的果蝇降落高度明显高于AD组(图3)。
图3淫羊藿素对Aβ诱导阿尔兹海默病果蝇飞行能力的影响(**P<0.01表示差异极显著，*P<0.05表示差异显著，NS表示差异无明显变化)。
实验结果说明：淫羊藿素显著提升Aβ诱导阿尔兹海默病果蝇飞行能力。
4、淫羊藿素显著抑制Aβ诱导阿尔兹海默病果蝇大脑氧化应激状态
按上述方式，实验共分为三组，分别为：野生型果蝇-WT组、阿尔兹海默病果蝇-AD组和淫羊藿素治疗阿尔兹海默病果蝇-ICT组。上述成年果蝇25天后，剥离每组果蝇大脑，在含有蛋白酶抑制剂的裂解液中使用组织匀浆器彻底匀浆，并在冰上孵育30分钟。然后将样品在4℃下以12000rpm离心10分钟，收集上清液用于分析活性氧(Reactive oxygenspecies，ROS)的含量和超氧化物歧化酶(Superoxide dismutase，SOD)的活性。
实验结果发现：WT组的果蝇ROS含量与ICT组无明显差异，WT组与ICT组的ROS含量明显低于AD组(图4)；WT组的果蝇SOD活性与ICT组无明显差异，WT组与ICT组的SOD活性明显高于AD组(图5)。
图4淫羊藿素对Aβ诱导阿尔兹海默病果蝇大脑ROS含量的影响(**P<0.01表示差异极显著，NS表示差异无明显变化)。
图5淫羊藿素对Aβ诱导阿尔兹海默病果蝇大脑SOD活性的影响(**P<0.01表示差异极显著，*P<0.05表示差异显著，NS表示差异无明显变化)。
实验结果说明：淫羊藿素显著抑制Aβ诱导阿尔兹海默病果蝇大脑氧化应激状态。
5、淫羊藿素显著改善Aβ诱导阿尔兹海默病果蝇大脑能量供应状态
按上述方式，实验共分为三组，分别为：野生型果蝇-WT组、阿尔兹海默病果蝇-AD组和淫羊藿素治疗阿尔兹海默病果蝇-ICT组。上述成年果蝇25天后，剥离每组果蝇大脑，在含有蛋白酶抑制剂的裂解液中使用组织匀浆器彻底匀浆，并在冰上孵育30分钟。然后将样品在4℃下以12000rpm离心10分钟，收集上清液用于分析ATP的含量变化。
实验结果发现：ICT组的果蝇ATP含量明显高于WT组，WT组的果蝇ATP含量明显高于AD组(图6)。
图6淫羊藿素对Aβ诱导阿尔兹海默病果蝇大脑ATP含量的影响(**P<0.01表示差异极显著)。
实验表明：淫羊藿素显著改善Aβ诱导阿尔兹海默病果蝇大脑能量供应状态。
6、淫羊藿素显著修复Aβ诱导阿尔兹海默病果蝇受损的线粒体结构
按上述方式，实验共分为三组，分别为：野生型果蝇-WT组、阿尔兹海默病果蝇-AD组和淫羊藿素治疗阿尔兹海默病果蝇-ICT组。上述成年果蝇25天后，剥离每组果蝇胸部组织，制作电镜样本，然后观察每组样本线粒体结构变化。
实验结果发现：WT组与ICT组的果蝇线粒体结构完整，AD组的果蝇线粒体结构破损严重(图7)。
图7淫羊藿素对Aβ诱导阿尔兹海默病果蝇受损线粒体结构的影响(其中：图7(a)WT组；图7(b)AD组；图7(c)ICT组；图中虚线标注的是每组果蝇的线粒体的情况，可以直观的看到：Aβ诱导阿尔兹海默病果蝇线粒体结构破损严重，淫羊藿素治疗后Aβ诱导阿尔兹海默病果蝇受损线粒体结构得到很好的修复)。
实验结果说明：淫羊藿素显著修复Aβ诱导阿尔兹海默病果蝇受损的线粒体结构。
7、淫羊藿素显著修复Aβ诱导阿尔兹海默病果蝇受损的线粒体功能
按上述方式，实验共分为三组，分别为：野生型果蝇-WT组、阿尔兹海默病果蝇-AD组和淫羊藿素治疗阿尔兹海默病果蝇-ICT组。上述成年果蝇25天后，新鲜分离的胸部组织在冰上的反应混合物(20mM HEPES，10mM KH2PO4，110mM蔗糖，20mM牛磺酸，60mM K-乳酸盐，0.5mM EGTA，3mM MgCl2，1g/L无脂肪酸BSA)中匀浆。线粒体呼吸链复合物的各种底物、解偶联剂和抑制剂如下：底物包括2M丙酮酸、0.8M苹果酸、2M谷氨酸、1M琥珀酸、0.5M ADP+Mg2+和4mM细胞色素C；解偶联剂包括1mM羰基氰化物间氯苯腙(CCCP)；抑制剂包括1mM鱼藤酮和5mM抗霉素A(AMA)。在丙酮酸、苹果酸、谷氨酸和ADP+Mg2+存在的情况下，在呼吸缓冲液中测量线粒体呼吸链复合物Ⅰ(ComplexⅠ)呼吸的具体情况。使用DatLab软件记录线粒体呼吸链复合物Ⅰ(ComplexⅠ)呼吸功能的氧浓度和氧通量。
实验结果发现：WT组的果蝇线粒体呼吸链复合物Ⅰ呼吸功能与ICT组无明显差异，WT组与ICT组的果蝇线粒体呼吸链复合物Ⅰ呼吸功能明显高于AD组(图8)。
图8淫羊藿素对Aβ诱导阿尔兹海默病果蝇线粒体呼吸链ComplexⅠ呼吸功能的影响(**P<0.01表示差异极显著，NS表示差异无明显变化)。
实验表明：淫羊藿素显著修复Aβ诱导阿尔兹海默病果蝇受损的线粒体功能。
结论：
1、图1显示淫羊藿素显著延长Aβarc果蝇寿命。
2、图2显示淫羊藿素显著提升Aβarc果蝇攀爬能力。
3、图3显示淫羊藿素显著提升Aβarc飞行能力。
4、图4显示淫羊藿素显著抑制了Aβarc果蝇大脑中增加的ROS含量，改善其氧化应激状态。
5、图5显示淫羊藿素显著修复了Aβarc果蝇大脑中受损的SOD活性，改善其氧化应激状态。
6、图6显示淫羊藿素显著恢复了Aβarc果蝇大脑中减少的ATP含量，挽救了Aβarc果蝇大脑受损的能量代谢，极大提高了Aβarc果蝇大脑能量(ATP)的供应。
7、图7显示淫羊藿素几乎完全修复了Aβarc果蝇受损的线粒体结构，是保障Aβarc果蝇能量供应和抑制其氧化应激的关键因素。
8、图8显示淫羊藿素挽救了Aβarc果蝇受损的线粒体功能，是保障Aβarc果蝇能量供应和抑制其氧化应激的关键因素。
上述说明是针对本发明较佳可行实施例的详细说明，但实施例并非用以限定本发明的专利申请范围，凡本发明所提示的技术精神下所完成的同等变化或修饰变更，均应属于本发明所涵盖专利范围。
Claims (3)
1.淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，其特征在于：所述药物组合物是以淫羊藿素为主要成分，加上药学中可接受的辅料或辅助性成分制备成临床上可接受的药物制剂，所述的淫羊藿素在其药物组合物中的含量为0.01-95％w/w。
2.根据权利要求1所述的淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，其特征在于：所述药物制剂包括口服制剂和注射制剂两种剂型。
3.根据权利要求2所述的淫羊藿素在制备抑制淀粉样蛋白Aβ诱导阿尔兹海默病药物中的应用，其特征在于：所述口服制剂为口服胶囊，所述注射制剂为静脉注射液。
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