CN116531474A - 具有改善学习记忆能力的药食两用组合物及其制备方法与应用 - Google Patents
具有改善学习记忆能力的药食两用组合物及其制备方法与应用 Download PDFInfo
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Abstract
本发明公开了一种具有改善学习记忆能力的药食两用组合物及其制备方法和应用,它由枸杞子1‑10份,黄精1‑10份,人参1‑5份,益智仁1‑5份制成。本发明提供的具有改善学习记忆能力的药食两用组合物,具有延缓与改善老年期痴呆症患者学习记忆能力,疗效可靠,安全性好,不良反应低,可用于制备延缓老年期痴呆症的保健食品或医药产品。
Description
技术领域
本发明涉及一种天然产物组合物,特别是涉及一种具有改善学习记忆能力的药食两用组合物及其制备方法。
背景技术
近年来研究资料显示,中国已进入了老龄化社会的发展趋势。中国当下已经有多于1.6亿多的老龄人口,并且每年增长的速度也在不断的增加。老龄人口的加速增长,尤其是年龄比较大的生活不能自理的老人数量与日俱增,导致养老问题成为社会关注的焦点问题。
研究显示,阿尔茨海默病是老年人高发疾病中最为常见的记忆力损伤疾病。阿尔茨海默病发病增长率惊人,给社会和家庭带来巨大的压力。阿尔茨海默病临床症状表现为以记忆力受损的记忆障碍、掌握运用新知识与社交能力下降等认知障碍,并伴随有抑郁、情感淡漠或焦躁不安、注意力涣散等精神障碍。阿尔茨海默病的神经病理变化主要表现为β淀粉样蛋白(amyloid-βpeptide,Aβ)在神经元细胞外异常沉积形成的老年斑(senileplaque,SP),同时存在大量的神经元纤维缠结(neurofibril tangle,NFT)。其发病机制极为复杂,目前主要有以下几点认识:(1)Aβ级联假说:AD患者脑内β-淀粉样蛋白(β-amyloid,Aβ)沉淀、聚集对已分化成熟神经元表现出显著的神经毒性,并且通过过度诱导ROS,加剧氧化应激反应,激活小胶质细胞,产生炎症因子加剧对神经元的损伤。(2)胆碱能假说:患者脑内胆碱能神经受损,乙酰胆碱含量不足,胆碱能神经失衡,加速Aβ的沉积,产生神经炎症,加剧神经元损伤。(3)神经炎症假说:在AD状态下,小胶质细胞释放促炎因子,进一步导致Aβ聚集、突触丢失,加剧神经元损伤。(4)氧化应激假说:AD发病过程中会产生大量的氧自由基,破坏细胞内外钙离子平衡,诱导脑内脂褐素的形成并沉积,加剧神经元损伤。总之,阿尔茨海默病的发病机制可归结为因衰老所致的脑内种种损伤因素增加,导致神经生长受损,影响神经传导功能的正常发挥,产生意识障碍。
阿尔茨海默病无法彻底根治,有效的前期预防,或延缓疾病进程,显得尤其重要。临床主要有(1)胆碱酯酶抑制剂,如多奈哌齐(donepezil),加兰他敏(galanthamine)、石杉碱甲(huperzine)、他克林(tacrine)等,旨在抑制乙酰胆碱酯酶活性,调节脑内神经递质水平,改善神经递质传递功能;(2)谷氨酸受体阻断剂,如美金刚(memantine)等,旨在减少谷氨酸的神经毒性;(3)自由基清除剂和抗氧剂,如司来吉兰(selegiline),旨在对抗氧自由基神经毒性;但这些药物有非常明显的副作用,除了会带来焦虑、恶心呕吐、失眠等不良影响外,他克林有严重的肝毒性,胆碱酯酶抑制剂还会带来心悸反应,司来吉兰更具有心毒性。因此,寻找更为安全有效的阿尔茨海默病预防与治疗药物迫在眉睫。更为重要的是,阿尔茨海默病重在预防与延缓疾病进程,需要长期服用,因此迫切需要安全性好,适合长期服用的医药健康产品。
发明内容
发明目的:本发明的目的在于提供一种疗效可靠,安全性好,具有很好的改善学习记忆能力的药食两用组合物。本发明的另一目的是提供上述组合物的制备方法和应用。
技术方案:为了实现以上目的,本发明采取的技术方案为:
一种具有改善学习记忆能力的药食两用组合物,它包括下列重量份数的原料:枸杞子1-10份,黄精1-10份,人参1-5份益智仁1-5份。
作为优选方案,以上所述的具有改善学习记忆能力的药食两用组合物,它包括下列重量份数的原料:枸杞子5份,黄精5份,人参3份,益智仁3份。
作为优选方案,以上所述的具有改善学习记忆能力的药食两用组合物,它包括下列重量份数的原料:取枸杞子8份,黄精2份,人参1份,益智仁1份。
作为优选方案,以上所述的具有改善学习记忆能力的药食两用组合物,它包括下列重量份数的原料:枸杞子2份,黄精2份,人参5份,益智仁5份。
发明优势:本发明是基于中医药理论与阿尔茨海默病的病理机制,获得的增强学习与记忆能力,改善阿尔茨海默病的有效药食两用组合物。
脑为元神之府,又为髓海,故本病病位在脑,又与心肝脾肾功能失调密切相关。年迈体虚,肝肾亏虚,精亏髓减,心脾受损,气虚血少,导致髓海空虚,神志失养,渐成痴呆。黄精与枸杞子均为中医添精填髓、滋补肝肾之要药,与阿尔茨海默症肾精亏虚、髓海失养的基本病机高度吻合。但肾精须得元气资助,方能化生气血濡养脏腑。人参大补元气,不仅使气血生化有源,还可推动气血上荣于脑。黄精与枸杞子虽均较为滋腻,有碍脾之嫌。年老之人本就脾肾渐衰,故辅以益智仁,温肾以助肾阳,暖脾以滋脾运,又取其芳香之气,补而不滞。四药相合,肾精得充,气血可化,神志可复。
本发明所述的具有改善学习记忆能力的药食组合物的制备方法,还包括以下步骤:
(1)取上述药材,混合,以水回流提取,过滤,收集滤液。
(2)取步骤(1)中的药渣,以水回流提取,过滤,收集滤液。
(3)取步骤(2)中的药渣,加水回流提取,过滤,收集滤液;
(4)取步骤(1)所得滤液,减压浓缩得浸膏;取步骤(2)所得滤液,减压浓缩得浸膏;取步骤(3)所得滤液,减压浓缩得浸膏,混合,低温减压制得提取物。
作为优选方案,步骤(1)所述的回流提取条件为:首先加入药材重量10倍体积量的提取溶剂水,100℃回流提取90min。步骤(2)所述的回流条件为:加入药材重量8倍体积量的提取溶剂水,100℃回流提取60min。步骤(3)所述的回流条件为:加入药材重量8倍体积量的水,100℃回流提取60min。
有益效果说明:本发明提供的药食两用组合物,通过中医临床经验总结与实验筛选获得。动物模型实验结果表明:本发明提供的药食两用组合物可有效改善阿尔茨海默病的主要病理环节,增强模型动物记忆能力,降低脑内β淀粉样蛋白含量,恢复胆碱能神经系统,降低海马组织致炎因子表达,调节动物氧化应激水平。与上市的OTC药物健延龄胶囊相比,本发明的药食两用组合物具有相似的效用,而组成更为简单,成本较低。细胞模型实验结果表明,本发明提供的药食两用组合物可提高神经细胞抗氧化损伤能力和抗炎性损伤能力,增加神经胶质细胞内神经营养因子的表达。
上述研究表明本发明提供的药食两用组合物对阿尔茨海默病有显著的改善作用,可用于制备具有改善阿尔茨海默病的医药健康产品,适合阿尔茨海默病患者。
本发明所述的具有改善学习记忆能力的药食两用组合物在制备改善阿尔茨海默病医药健康产品的应用,将此药食两用组合物和药学上可接受的载体制成片剂、丸剂、散剂、汤剂、颗粒剂、煎膏剂或浸膏剂剂型的药物,临床服用方便,并且本发明提供的药食两用组合物安全性好,适合长期服用。
附图说明
图1-3为药食两用组合物对D-半乳糖衰老模型小鼠潜伏期、上台前路程、穿越次数影响的柱状图。
图4为药食两用组合物对D-半乳糖衰老模型小鼠脑内Aβ水平影响柱状图。
图5-6为药食两用组合物对D-半乳糖衰老模型小鼠脑内AchE活力和Ach含量影响的柱状图。
图7-9为药食两用组合物对D-半乳糖衰老模型小鼠脑内IL-1β、IL-6、TNF-a水平影响的柱状图。
图10-12为药食两用组合物对D-半乳糖衰老模型小鼠血清中IL-1β、IL-6、TNF-a水平影响的柱状图。
图13-15为药食两用组合物对D-半乳糖衰老模型小鼠脑内MDA含量、SOD活力、GSH含量影响的柱状图。
图16为药食两用组合物对大鼠皮层星型胶质细胞内BDNF、GDNF、NGF表达影响的柱状图。
图17为药食两用组合物对TBHP氧化损伤HT22细胞保护作用的柱状图。
图18为药食两用组合物对致炎培养基损伤HT22细胞保护作用的柱状图。
具体实施方式
下面结合具体实施例进一步阐明本发明,应理解这些实施例仅用于说明本发明而不用于限制本发明的范围,在阅读了本发明之后,本领域技术人员对本发明的各种等价形式的修改均落于本申请所附权利要求所限定的范围。
实施例1
一种具有增强记忆,改善抑郁情绪作用的药食两用组合物的制备方法,包括如下步骤:
(1)取枸杞子8份,黄精2份,人参1份,益智仁1份,混合。加入药材重量10倍量的水回流提取90min,过滤,收集滤液和滤渣。
(2)取步骤(1)中的药渣,加入药材重量8倍体积量的水回流提取60min,过滤,收集滤液。
(3)取步骤(2)中的药渣,加入药材重量8倍体积量的水回流提取60min,过滤,收集滤液。
(4)合并步骤(1)、步骤(2)和步骤(3)中所得滤液,减压浓缩得浸膏,低温减压制得提取物。
实施例2
一种具有增强记忆,改善抑郁情绪作用的药食两用组合物的制备方法,包括如下步骤:
(1)取枸杞子2份,黄精2份,人参5份,益智仁5份,混合。加入药材重量10倍量的水回流提取90min,过滤,收集滤液和滤渣。
(2)取步骤(1)中的药渣,加入药材重量8倍体积量的水回流提取60min,过滤,收集滤液。
(3)取步骤(2)中的药渣,加入药材重量8倍体积量的水回流提取60min,过滤,收集滤液。
(4)合并步骤(1)、步骤(2)和步骤(3)中所得滤液,减压浓缩得浸膏,低温减压制得提取物。
实施例3
一种具有增强记忆,改善抑郁情绪作用的药食两用组合物的制备方法,包括如下步骤:
(1)取枸杞子5份,黄精5份,人参3份,益智仁3份,混合。加入药材重量10倍量的水回流提取90min,过滤,收集滤液和滤渣。
(2)取步骤(1)中的药渣,加入药材重量8倍体积量的水回流提取60min,过滤,收集滤液。
(3)取步骤(2)中的药渣,加入药材重量8倍体积量的水回流提取60min,过滤,收集滤液。
(4)合并步骤(1)、步骤(2)和步骤(3)中所得滤液,减压浓缩得浸膏,低温减压制得提取物。
实施例4本发明药食两用组合物抗阿尔茨海默病实验研究
一、实验材料与药物
1.药物和试剂
D-半乳糖购自阿拉丁试剂(上海)有限公司。超氧化物歧化酶(SOD)试剂盒、谷胱甘肽(GSH)试剂盒、丙二醛(MDA)试剂盒均购自南京建成生物工程研究所;Aβ试剂盒、乙酰胆碱酯酶(AchE)试剂盒、乙酰胆碱(Ach)试剂盒均购自艾方生物科技有限公司;白介素-6(IL-6)试剂盒、白介素-1β(IL-1β)试剂盒、肿瘤坏死因子(TNF-α)试剂盒均购自南京金益柏生物科技有限公司。多奈哌齐(GD18339)购自萨恩化学技术有限公司。健延龄胶囊购自雷允上药业集团有限公司(批号107289)。
2.实验仪器
水迷宫行为测试仪(上海吉量仪器有限公司);酶标仪(美国Perkin-Elmer公司);BT125型电子天平(赛多利斯科学仪器有限公司);KQ-250E型超声波清洗器(昆山禾创超声仪器有限公司);Anke GL-16GII型离心机(上海安亭科学仪器厂)。
3.实验动物
SPF级雄性昆明种小鼠,体重18~22g,购自上海斯莱克实验动物有限责任公司,合格证号SCXK(京)2019-0010。
二、实验方法
1.小鼠D-半乳糖衰老模型的建立与药食两用组合物给药
健康小鼠适应性喂养5d后,小鼠随机分为空白组、模型组、阳性对照组和受试药食两用组合物(实施例3)低剂量组(1.33g/kg)、高剂量组(2.67g/kg),每组7只,经称重显示各组间体重差异无统计学意义。除空白组外,其余各组用D-半乳糖损伤造成记忆损伤,具体方式为小鼠每天皮下注射D-半乳糖(600mg/kg)连续6周。模型组给以等体积生理盐水。阳性对照组给以多奈哌齐(2mg/kg);对比药物给以健延龄胶囊(3.28g/kg)。其余各组给以本发明实施例3制备得到的中药组合物的提取物30d,进行系列测试。
2.药效评价方法
(1)行为学测试方法
6周D-半乳糖损伤造模结束后,进行连续4天的Morris水迷宫定位航行实验,以测试其空间记忆能力。将水迷宫内水温控制在20-22℃,水深约20cm,保持学习、训练和测试时水迷宫平台和周围物体位置固定不变。让小鼠在水迷宫内自由游120s,然后引导其找到水下平台,让其处于平台上10s。此操作一天进行2次,时间间隔2h以上。每天训练2个象限,训练共4天。第5天开始正式测试。让小鼠从平台所在象限对侧象限的最远点背对平台入睡,拍摄记录小鼠找到平台的全过程。第6天撤除目标象限的站台进行测试,记录小鼠穿越站台的次数。以各组小鼠自水迷宫起点游至平台终点所需的时间(潜伏期)、路程和穿越台子次数为衡量小鼠学习获得与记忆巩固能力的指标。
(2)生化指标测试
水迷宫测试结束后,取小鼠海马部位,测定海马中Aβ含量,乙酰胆碱酯酶(AchE)和乙酰胆碱(Ach)活力;测定氧化应激标志物水平:超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA);同时也测定海马匀浆测定炎性因子水平:白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子(TNF-α)。
取小鼠血清,测定血清中炎性因子水平:白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子(TNF-α)。
3.统计学处理
所有实验数据均采用SPSS18.0统计处理软件进行统计学处理,结果以表示,组间差异采用t检验,P<0.05为差异有统计学意义。
三、实验结果
1.药食两用组合物对D-半乳糖衰老模型小鼠学习记忆的影响
D-半乳糖损伤6周后,进行水迷宫实验测试。由图1-3可以看出小鼠经D-半乳糖损伤后,模型组小鼠较空白组小鼠潜伏期显著延长(P<0.05),上台次数显著减少(P<0.05),上台前路程显著增加(P<0.05),经灌胃本发明提供的药食两用组合物后,潜伏期显著缩短,上台次数显著增加,上台前路程显著减少,表明本发明所提供的药食两用组合物具有很好的对抗衰老损伤因素,改善学习记忆的功效。
2.药食两用组合物对D-半乳糖衰老模型小鼠海马组织中Aβ水平的影响
小鼠进行完行为学测试后,解剖分离动物脑组织,测定小鼠脑内Aβ含量,结果如图4所示。与正常组小鼠相比,模型组小鼠海马中Aβ含量显著上升,给予本发明实施例3药食两用组合物后可显著降低海马组织中Aβ的表达。表明本发明所提供的药食两用组合物具有很好的降低衰老模型动物脑内Aβ水平,改善学习记忆能力的作用。
3.药食两用组合物对D-半乳糖衰老模型小鼠海马组织中AchE和Ach水平的影响
解剖动物取脑,制得匀浆,根据试剂盒的操作方法,测定小鼠脑内AchE和Ach的活力。结果如图5-6所示,与正常组小鼠相比,模型组小鼠海马中AchE含量显著升高,Ach含量显著降低,给予本发明实施例3药食两用组合物后,可显著下调AchE的表达,显著提高Ach的活力,表明本发明所提供的药食两用组合物具有调节衰老模型动物脑内神经递质水平,改善神经传导功能的作用。
4.药食两用组合物对D-半乳糖衰老模型小鼠海马组织中炎性因子表达的影响
小鼠进行完行为学测试后,处死取脑,制得匀浆,依据相应试剂盒的操作方法,测量小鼠脑内IL-6、IL-1β、TNF-a的水平。由图7-9可以看出,小鼠经D-半乳糖损伤后,与空白组相比,模型组小鼠脑内IL-6、IL-1β和TNF-a含量显著上升(P<0.05)。给予本发明实施例3药食两用组合物后,可显著下调模型动物海马组织中IL-6、IL-1β和TNF-a表达,其作用趋势与阳性药多奈哌齐作用相当。表明本发明所提供的药食两用组合物具有很好的降低衰老模型动物脑内炎性因子水平,改善炎性损伤的作用。
5.药食两用组合物对D-半乳糖衰老模型小鼠海马组织中氧化因子的影响
小鼠进行完行为学测试后,处死取脑,制得匀浆,依据相应试剂盒的操作方法,测量小鼠脑内SOD、MDA、GSH的水平。由图10-12可以看出,与正常组小鼠相比,模型组小鼠脑内抗氧化关键因子超氧化物歧化酶(SOD)、谷胱甘肽(GSH)含量显著降低(P<0.05),氧化产物丙二醛(MDA)含量显著升高;给予实施例3药食两用组合物后,可显著改善上述趋势,其作用趋势与阳性药多奈哌齐及健延龄胶囊作用相当。表明本发明所提供的药食两用组合物具有很好的抗氧化作用。
6.药食两用组合物对D-半乳糖衰老模型小鼠血清中炎性因子表达的影响
小鼠进行完行为学测试后,取血清,依据相应试剂盒的操作方法,测量小鼠血清中IL-6、IL-1β、TNF-a的水平,如图13-15所示,模型组小鼠较正常组小鼠血清中IL-6、IL-1β、TNF-a的含量显著上升(P<0.05),给予实施例3药食两用组合物后,可显著改善上述趋势。提升本发明所提供的药食两用组合物具有显著的调控衰老动物免疫机能,对抗机体慢性炎症的作用。
实施例5体外神经营养实验研究
一、实验材料与药物
1.实验仪器
二氧化碳培养箱(Forma seriesⅡwater jacket CO2 incubator,Thermo公司),1300series A2超净工作台(Thermo公司),Auto Vert A1倒置荧光显微镜(ZEISS公司),Nanodrop(DS11 spectrophotometer,DeNovix公司),ABI7500荧光实时定量PCR仪(Invitrogen公司),高速离心机(Allegra X-12R Centrifuge和Microfuge 22RCentrifuge,Backman公司),恒温水浴锅(Bluepard公司),恒温振荡器(IS-RDV1 incubatorshaker,CRYSTAL公司),细胞培养器皿(CORNING公司)。
2.试剂
TRIzol RNA提取试剂盒(15596-026,Invitrogen),RT-PCR反转录试剂盒(PrimeScriptTM RT reagent Kit with gDNA Eraser,RR047A,TAKARA),SYBR荧光定量PCR试剂(FastStart Universal SYBR Green Master(ROX),04913914001,Roche),Bradford试剂(T9310A,TAKARA)。
3.细胞株
大鼠胶质细胞(C6)细胞株,来源于自ATCC细胞库。
二、实验方法
1.细胞培养与给药
将C6细胞按接种量1×105个/孔接种于6孔板中培养24h后,对照组24h换一次新鲜培养液,培养24h。样品组加实施例3中药食两用组合物高剂量、中剂量、低剂量(20、6、3ug/mL)阳性药组:加Forskolin(40nM)培养24h。
2.实时定量荧光PCR仪测定神经营养因子转录水平表达
RNA提取:吸去细胞培养液,加入1mL的PBS冲洗,每盘细胞中加入300μL的TRIzol,按TRIzol RNA提取试剂盒所列步骤进行操作。所提取RNA于-80℃保存。
cDNA的制备:用Nanodrop测试RNA的浓度和纯度,根据TaKaRa逆转录试剂盒的说明,总计取用1μg的RNA来进行逆转录的操作。
依照SYBR荧光实时定量试剂盒操作步骤,利用荧光实时定量PCR仪测定神经营养因子的基因转录水平表达。所用引物序列如下:
表1引物序列
3.统计学处理
所有实验数据均采用SPSS18.0统计处理软件进行统计学处理,结果以表示,组间差异采用t检验,P<0.05为差异有统计学意义。
三、实验结果
将体外培养的C6大鼠胶质细胞,加以不同比例的药食两用组合物24h后,利用qPCR技术检测细胞内BDNF的表达。如图16所示,实施例3中各药食两用组合物可以显著促进C6大鼠胶质细胞内BDNF、GDNF、NGF的表达,表现出较好的神经营养活性。
实施例6体外抗氧化神经损伤实验研究
一、实验材料与药物
1.实验仪器
二氧化碳培养箱(Forma seriesⅡwater jacket CO2 incubator,Thermo公司),1300series A2超净工作台(Thermo公司),Auto Vert A1倒置荧光显微镜(ZEISS公司),恒温水浴锅(Bluepard公司),多功能酶标仪(Enspire,Perkin Elmer公司),细胞培养器皿(CORNING公司)。
2.试剂
MTT(Salibro公司),叔丁基双氧水(TBHP)(tert-Butyl hydroperoxidesolution,STBH 3911,ALDRICH)。细胞培养基与所用试剂购自Invitrogen公司。
3.细胞株
小鼠海马神经元细胞(HT22)细胞株,来源于自ATCC细胞库。
二、实验方法
1.细胞培养与给药
将HT22细胞按接种量1.5×103个/孔接种于96孔板中培养24h后,对照组每24h换一次新鲜培养液,培养24h。模型组按对照组的方法培养24小时后加TBHP(0.3mM)继续培养3h。样品组组按对照组的方法培养24小时后,样品组药物和TBHP共同作用,样品组加实施例3中药食两用组合物高剂量、中剂量、低剂量(20、6、3ug/mL)和TBHP培养3h。
2.MTT法测定细胞存活率
培养结束后,每孔加入10μL MTT溶液(5mg/mL))。3h后弃去培养液,加入150μL二甲亚砜溶解细胞,充分振荡30min后在570nm波长处测定各孔的吸收值。细胞存活率由以下公式计算:细胞存活率=(实验组A570/对照组A570)×100%。
3.统计学处理
所有实验数据均采用SPSS18.0统计处理软件进行统计学处理,结果以表示,组间差异采用t检验,P<0.05为差异有统计学意义。
三、实验结果
将体外培养的HT22,经过TBHP损伤,加以实施例3中的药食两用组合物培养后,如图17所示,各药食两用组合物可以显著对抗TBHP所致的细胞损伤,表现出较好的抗氧化损伤,保护神经的活性。
实施例7体外抗炎性损伤实验研究
一、实验材料与药物
1.实验仪器
二氧化碳培养箱(Forma seriesⅡwater jacket CO2 incubator,Thermo公司);1300series A2超净工作台(Thermo公司);Auto Vert A1倒置荧光显微镜(ZEISS公司);恒温水浴锅(Bluepard公司);多功能酶标仪(Enspire,Perkin Elmer公司);细胞培养器皿(CORNING公司)。
2.试剂
MTT(Salibro公司),脂多糖Lipopolysaccharides(LPS)(14011S)购自CST公司,SYBR荧光定量PCR试剂(FastStart Universal SYBR Green Maste(ROX),04913914001,Roche)。Bradford试剂盒(T9310A,TAKARA)。细胞培养基购自Invitrogen公司。细胞培养所用试剂均购自Sigma公司。
3.细胞株
小鼠海马神经元细胞(HT22)细胞株,小鼠小胶质细胞(BV2)细胞株,均来源于ATCC细胞库。
二、实验方法
1.细胞培养与给药
炎性培养基构建:LPS(1μg/mL)损伤BV2细胞,收取上清,配置成90%炎性培养基损伤细胞。
将HT22细胞按接种量1.5×103个/孔接种于96孔板中培养24h后,对照组每24h换一次新鲜培养液,培养24h。模型组按对照组的方法培养24小时后炎性培养基继续培养24h。样品组组按对照组的方法培养24小时后,样品组药物与炎性培养基共同作用,样品组加实施例3药食两用组合物高剂量、中剂量、低剂量(20、6、3ug/mL)和炎性培养基培养24h。
培养结束后,每孔加入10μL MTT溶液(5mg/mL)。3h后弃去培养液,加入150μL二甲亚砜溶解细胞,充分振荡30min后在570nm波长处测定各孔的吸收值。细胞存活率由以下公式计算:细胞存活率=(实验组A570/对照组A570)×100%。
3.统计学处理
所有实验数据均采用SPSS18.0统计处理软件进行统计学处理,结果以表示,组间差异采用t检验,P<0.05为差异有统计学意义。
三、实验结果
将体外培养的HT22,经过炎性损伤,加以实施例3中的药食两用组合物培养后,如图18所示,各药食两用组合物可以显著对抗炎性因子所致的细胞损伤,表现出较好的抗炎性损伤,保护神经的活性。
以上实验结果表明,本发明提供的药食两用组合物具有显著的改善D半乳糖所致的记忆损伤、营养神经元,改善神经元氧化和炎性损伤等功能,表明本发明提供的药食两用组合物具有很好的改善阿尔茨海默病的作用。与现有的改善阿尔茨海默病的化学药物相比,该组合物具有多靶点的作用特点,改变了以往药物仅作用于炎性损伤、氧化损伤等单一靶点,尤其具有显著的神经营养功能。具有较高的药物开发价值。
以上所述仅是本发明的优选实施方式,应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (8)
1.一种具有改善学习记忆能力的药食两用组合物,其特征在于,它包括下列重量份数的原料:枸杞子1-10份,黄精1-10份,人参1-5份,益智仁1-5份。
2.根据权利要求1所述的具有改善学习记忆能力的药食两用组合物,其特征在于,它包括下列重量份数的原料:枸杞子5份,黄精5份,人参3份,益智仁3份。
3.根据权利要求1所述的具有改善学习记忆能力的药食两用组合物,其特征在于,它包括下列重量份数的原料:取枸杞子8份,黄精2份,人参1份,益智仁1份。
4.根据权利要求1所述的具有改善学习记忆能力的药食两用组合物,其特征在于,它包括下列重量份数的原料:枸杞子2份,黄精2份,人参5份,益智仁5份。
5.权利要求1至4任一项所述的改善学习记忆能力的药食两用组合物的制备方法,其特征在于,它包括以下步骤:
(1)按重量份数取枸杞子、黄精、人参、益智仁,混合,加水回流提取,得提取液,过滤,收集滤液和滤渣;
(2)取步骤(1)中的药渣,加水回流提取,过滤,收集滤液;
(3)取步骤(2)中的药渣,加水回流提取,过滤,收集滤液;
(4)取步骤(1)所得滤液,减压浓缩得浸膏;取步骤(2)所得滤液,减压浓缩得浸膏;取步骤(3)所得滤液,减压浓缩得浸膏,混合,制得提取物。
6.根据权利要求5所述的具有改善学习记忆能力的药食两用组合物的制备方法,其特征在于,步骤(1)所述的回流提取条件为:加入药材重量10倍体积量的水,100℃回流提取90min;步骤(2)所述的回流提取条件为:加入药材重量8倍体积量的水,100℃回流提取60min;步骤(3)所述的回流提取条件为:加入药材重量8倍体积量的水,100℃回流提取60min。
7.权利要求1至4任一项所述的药食两用组合物在制备防治老年期痴呆症保健食品或医药产品中的应用。
8.根据权利要求7所述的应用,其特征在于,将药食两用组合物的提取物和药学上可接受的载体制成片剂、丸剂、散剂、汤剂、颗粒剂、煎膏剂或浸膏剂的药物。
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