CN104082659B - 增强记忆的组合物及其应用 - Google Patents
增强记忆的组合物及其应用 Download PDFInfo
- Publication number
- CN104082659B CN104082659B CN201410264474.7A CN201410264474A CN104082659B CN 104082659 B CN104082659 B CN 104082659B CN 201410264474 A CN201410264474 A CN 201410264474A CN 104082659 B CN104082659 B CN 104082659B
- Authority
- CN
- China
- Prior art keywords
- coriolan
- group
- memory
- dementia
- model
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000015654 memory Effects 0.000 title claims abstract description 23
- 239000000203 mixture Substances 0.000 title claims abstract description 12
- 239000009429 Ginkgo biloba extract Substances 0.000 claims abstract description 31
- 229940068052 ginkgo biloba extract Drugs 0.000 claims abstract description 31
- 235000020686 ginkgo biloba extract Nutrition 0.000 claims abstract description 31
- 239000003814 drug Substances 0.000 claims description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 38
- 206010012289 Dementia Diseases 0.000 abstract description 37
- 239000000890 drug combination Substances 0.000 abstract description 15
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 abstract description 14
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 abstract description 14
- 210000005013 brain tissue Anatomy 0.000 abstract description 13
- 238000011534 incubation Methods 0.000 abstract description 13
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 abstract description 11
- 241000699670 Mus sp. Species 0.000 abstract description 11
- 210000004027 cell Anatomy 0.000 abstract description 10
- 229930003944 flavone Natural products 0.000 abstract description 7
- 235000011949 flavones Nutrition 0.000 abstract description 7
- 230000004044 response Effects 0.000 abstract description 7
- 238000005728 strengthening Methods 0.000 abstract description 7
- 230000006872 improvement Effects 0.000 abstract description 6
- 241000218628 Ginkgo Species 0.000 abstract description 5
- 230000006886 spatial memory Effects 0.000 abstract description 5
- 101800000263 Acidic protein Proteins 0.000 abstract description 4
- 230000002159 abnormal effect Effects 0.000 abstract description 4
- 239000004480 active ingredient Substances 0.000 abstract description 4
- 239000000284 extract Substances 0.000 abstract description 4
- 241000233866 Fungi Species 0.000 abstract description 2
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 abstract description 2
- -1 flavone compound Chemical class 0.000 abstract description 2
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 abstract description 2
- 238000012360 testing method Methods 0.000 description 18
- 238000000034 method Methods 0.000 description 9
- 238000010586 diagram Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 150000002213 flavones Chemical class 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 235000011201 Ginkgo Nutrition 0.000 description 3
- 235000008100 Ginkgo biloba Nutrition 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 229960003980 galantamine Drugs 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000003446 memory effect Effects 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 238000012549 training Methods 0.000 description 3
- 238000012347 Morris Water Maze Methods 0.000 description 2
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000002079 cooperative effect Effects 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 230000006386 memory function Effects 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 238000009116 palliative therapy Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 description 1
- 206010063409 Acarodermatitis Diseases 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 206010008096 Cerebral atrophy Diseases 0.000 description 1
- LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 description 1
- 102000003914 Cholinesterases Human genes 0.000 description 1
- 108090000322 Cholinesterases Proteins 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 229940122601 Esterase inhibitor Drugs 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- ZQPQGKQTIZYFEF-WCVJEAGWSA-N Huperzine Natural products C1([C@H]2[C@H](O)C(=O)N[C@H]2[C@@H](O)C=2C=CC=CC=2)=CC=CC=C1 ZQPQGKQTIZYFEF-WCVJEAGWSA-N 0.000 description 1
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 241000447727 Scabies Species 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000222355 Trametes versicolor Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000007131 anti Alzheimer effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 201000004559 cerebral degeneration Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 229940048961 cholinesterase Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 231100000317 environmental toxin Toxicity 0.000 description 1
- 239000002329 esterase inhibitor Substances 0.000 description 1
- BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 208000005687 scabies Diseases 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Alternative & Traditional Medicine (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
增强记忆的组合物及其应用，组合物的有效成分为云芝多糖和银杏黄酮。分别提取药用真菌云芝多糖，天然药用植物银杏叶中的黄酮类化合物，云芝多糖与银杏黄酮联合用药时，可显著性缩短痴呆小鼠的逃避潜伏期、提高空间记忆能力、增加正确反应次数、延长首次犯错潜伏期、减少错误次数及减轻脑组织细胞状态异常及，并显著降低胶原纤维酸性蛋白GFAP的表达，对痴呆模型小鼠的记忆有一定的改善作用。
Description
技术领域
本发明属于生物医学和食品保健技术领域，具体涉及一种增强记忆的组合物及其应用。
背景技术
老年痴呆症，主要表现为阿兹海默症(Alzheimer’s disease,AD)，或称脑退化症，是一种持续性神经功能障碍。AD是一种以进行性认知障碍和记忆力损害为主的中枢神经系统退行性疾病，主要病理特征为大脑萎缩、脑组织内老年斑，脑血管沉积物和神经元纤维缠结。后期主要为中枢一些部位胆碱能功能不足，故胆碱能增强药是目前主要的治疗药物，如胆碱酯酶抑制剂多奈哌齐、石杉碱甲、加兰他敏、卡巴拉汀等。然而，胆碱酯酶(AChE)抑制剂只是一种能够暂时性改善认知功能的姑息性治疗策略，随着对AD病理生理的分子和细胞学机制研究的深入，寻找其他可能延缓病程进展的药物干预手段显得尤为重要。AD的发生包括遗传因素、慢性感染、免疫缺陷和环境毒素等多种原因，临床表现为进行性精神状态衰退，包括记忆、智力、定向、判断能力、情感障碍和行为失常甚至发生意识模糊等。患者通常在发病后5-6年内死于继发感染和全身衰竭。建立合理的病症结合动物模型对于抗AD药物筛选具有重要意义。单因素造模法模型基础较简单，以D-半乳糖注射、Aβ诱发、化学性胆碱能神经损伤、慢性铝中毒为主要的造模方法。常见的复合因素造模法有D-半乳糖致衰老为基础的及Aβ注射联合其他因素建立的AD中医病证模型，其中，以D-半乳糖联合AlCl3可诱导模拟肾虚痰阻型AD模型。
云芝多糖是云芝提取物中的主要活性成份，是含有蛋白质的葡聚糖。云芝多糖的抗肿瘤作用、免疫增强作用和保护肝脏的作用已普遍用于临床。近年来有研究显示云芝多糖对小鼠和大鼠的学习记忆功能亦有一定的改善作用。而银杏黄酮是银杏叶的提取物，研究证明银杏黄酮具有改善人体心血管功能,降血脂,提高机体免疫机能和增强记忆力作用。多种生物活性物质的复配经常能进一步提高其作用，但到目前为止，还没有利用云芝多糖和银杏黄酮复配物来进行改善记忆的研究被报道。本专利主要对云芝多糖和银杏黄酮复配物对增强记忆作用进行了研究。
发明内容
解决的技术问题：本发明提供了一种增强记忆的组合物及其应用，旨在弥补现有技术提供的用于增强记忆的药物依赖性强、副作用大、姑息性治疗等不足。
技术方案：增强记忆的组合物，有效成分为云芝多糖和银杏黄酮。
优选的，所述云芝多糖和银杏黄酮的质量比为(1-9):(9-1)。
进一步优选的，所述云芝多糖和银杏黄酮的质量比为1:1。
上述组合物在制备治疗阿兹海默症药物中的应用。
上述组合物在制备增强记忆药物中的应用。
治疗阿兹海默症药物，有效成分为上述组合物。
有益效果：本发明提供的一种云芝多糖与银杏黄酮的复配物及其增强记忆的应用，该组合物采用云芝多糖与银杏黄酮联合经口给药，增强痴呆模型小鼠的记忆能力。分别提取药用真菌云芝多糖，天然药用植物银杏叶中的黄酮类化合物。云芝多糖与银杏黄酮联合用药时，可显著性缩短痴呆小鼠的逃避潜伏期、提高空间记忆能力、增加正确反应次数、延长首次犯错潜伏期、减少错误次数及减轻脑组织细胞状态异常及，并显著降低胶原纤维酸性蛋白GFAP的表达，对痴呆模型小鼠的记忆有一定的改善作用。
附图说明
图1为第六天各组小鼠第四象限停留时间百分率、穿越原平台次数对照示意图(n＝8)；其中A为第四象限停留时间百分率对照示意图；B为穿越原平台次数对照示意图；注：与正常对照组比较，***p<0.001；与痴呆模型组比较，#p<0.05，##p<0.01，###p<0.001；
图2为Y迷宫试验各组小鼠正确反应次数对照示意图(n＝8)；注：与正常对照组比较，***p<0.001；与痴呆模型组比较，#p<0.05,###p<0.001；
图3为避暗试验各组小鼠潜伏期和错误次数对照示意图(n＝8)；其中A为潜伏期对照示意图，B为错误次数对照示意图；注：与正常对照组比较，**p<0.01，***p<0.001；与痴呆模型组比较，#p<0.05，###p<0.001；
图4为各组小鼠脑组织形态学变化对照图(200×)；
图5为各组小鼠脑组织GFAP表达情况对照图(400×)；
图6为各组小鼠脑组织GFAP表达量对照图；
图7为各组小鼠脑组织GFAP表达量对照柱状图；注：与正常对照组比较，***p<0.001；与痴呆模型组比较，###p<0.001。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白，以下结合附图及实施例，对本发明进行进一步的详细说明。应当理解，此处所描述的具体实施例仅仅用以解释本发明，并不用于限定发明。
本发明的目的在于提供一种增强痴呆模型小鼠记忆的方法，该方法采用云芝多糖与银杏黄酮联合经口给药，改善痴呆模型小鼠的记忆功能。
在本发明实施例中，云芝多糖中多糖含量为30wt.％，银杏黄酮中黄酮含量为25wt.％。
在本发明实施例中，云芝多糖与银杏黄酮联合用药时的用药剂量为：云芝多糖150mg/kg/d、银杏黄酮150mg/kg/d。
在本发明实施例中，云芝多糖与银杏黄酮联合用药时，可显著性缩短痴呆小鼠的逃避潜伏期、提高空间记忆能力、增加正确反应次数、延长首次犯错潜伏期、减少错误次数及减轻脑组织细胞状态异常及，并显著降低胶原纤维酸性蛋白GFAP的表达。
在本发明实施例中，云芝多糖与银杏黄酮联合经口给药对痴呆模型小鼠记忆有改善作用。
实施例1：
下面结合附图及具体实施例对本发明的应用原理作进一步描述。
一、实验目的
观察云芝多糖与银杏黄酮联合经口给药对痴呆模型小鼠记忆的改善作用。
二、实验材料
1.受试药物
云芝多糖：多糖含量：30wt.％
银杏黄酮：黄酮含量：25wt.％
阳性对照药：氢溴酸加兰他敏(西安杨森制药有限公司，规格：28片/盒，8mg/片，批号：111012730，适应症：用于治疗轻度到中度阿尔茨海默型痴呆症状。)
2.实验动物
2.1来源、种属、品系、合格证：扬州大学比较医学中心，清洁级ICR小鼠，96只，动物合格证号：SCXK(苏)2012-0004。
2.2体重：20±2g
2.3性别：雌雄各半
2.4各组动物数：8只/组
2.5饲养：动物饲养于22±3℃，相对湿度40-75％，昼夜明暗交替时间12h，动物自由摄食、饮水，适应性饲养7天后用于实验。
3.主要试剂
D-半乳糖，中国惠兴生化试剂有限公司，规格：25g/瓶，批号：120916；无水氯化铝(AlCl3)，国药集团化学试剂有限公司，规格：500g/瓶，批号：20120106。
4.主要仪器
Sartorius BT125D分析天平：赛多利斯科学仪器(北京)有限公司；Morris水迷宫：上海吉量软件科技有限公司；Y迷宫：淮北正华实验仪器公司；避暗仪：淮北正华实验仪器公司；电泳仪：北京市六一仪器厂。
三、实验方案
1.动物分组:将96只ICR小鼠，雌雄各半，随机分为6组,每组16只。分别为：
正常对照组:自来水；
痴呆模型组:自来水；
云芝多糖单用组：300mg/kg/d，多糖含量：30wt.％(英骏生物技术有限公司)；
银杏黄酮单用组：300mg/kg/d，黄酮含量：25wt.％(英骏生物技术有限公司)；
云芝多糖与银杏黄酮联合用药组(联合用药组)：云芝多糖150mg/kg/d+银杏黄酮150mg/kg/d；
阳性对照组：氢溴酸加兰他敏6mg/kg/d；
2.造模和给药:除正常对照组给予普通饮用水，其他各组每天给予0.50mg/ml的AlCl3溶液作为饮用水，同时每日上午腹腔注射10.0mg/ml的D-半乳糖生理盐水溶液(给药体积，0.1ml/10g；给药剂量，100mg/kg/d),连续造模54天后，进行水迷宫测试，连续6天，确定模型。
3.检测指标:每日下午灌胃给予受试药物，第54天开始，每日给药后2h，各组小鼠进行水迷宫测试，连续6天。第7天进行Y迷宫测试，连续2天。第9天进行避暗试验，连续2天。第11天给药后2h后处死动物，取脑组织，每组3只福尔马林固定，脑组织切片后免疫组化检测胶质细胞原纤维酸性蛋白GFAP表达，其余组织匀浆作Western blot检测。
四、统计学处理方法
实验数据用SPSS11.5软件处理，多组样本均数间比较用Dunnett t检验，不符合t检验条件的样本用Tamhane-T2检验。所有数据均用均数±标准差()表示。p<0.05表示有显著性差异，p<0.01表示有极显著性差异。
五、实验结果
1.受试药各组对实验性痴呆模型小鼠认知障碍的影响
表1可见平台训练各组小鼠潜伏期(n＝8)
由表1可见，在Morris水迷宫试验中，各组小鼠的训练潜伏期相近，说明各组小鼠的视觉、活动能力以及对目标的识别能力均正常。
表2隐蔽平台试验各组小鼠潜伏期(n＝8)
注：与正常对照组比较，***p<0.001；与痴呆模型组比较，#p<0.05。
由表2可见，在之后3天的隐蔽平台试验中，痴呆模型组小鼠的潜伏期显著长于正常对照组，联合用药组能明显缩短痴呆模型小鼠的潜伏期，提高小鼠的学习记忆能力，存在协同效应。
由图1可见，在第6天的空间探索试验中，痴呆模型组小鼠在第四象限停留时间百分率以及穿越原平台次数均显著低于正常组，云芝多糖单用组能够增加痴呆模型小鼠的第四象限停留时间百分率，阳性对照组、银杏黄酮单用组、联合用药组能显著增加痴呆模型小鼠的第四象限停留时间百分率及穿越原平台次数，联合用药组提高AD模型小鼠的空间记忆能力，存在协同效应。
由图2可见，在Y迷宫试验中，第一天的学习训练试验，各组小鼠的正确反应次数无显著性差异。而在第二天的测试试验中，与正常对照组相比，痴呆模型组小鼠测试10次中的正确反应次数显著降低，而联合用药组能够显著增加痴呆模型小鼠的正确反应次数，存在协同效应。
由图3可见，在第一天学习训练中，各组小鼠的潜伏期无明显差异。第二天测试结果显示，痴呆模型组小鼠的潜伏期显著短于正常对照组，而错误次数显著多于正常对照组。各受试药组均可减少痴呆模型小鼠的错误次数，联合用药组能够显著延长痴呆模型小鼠的潜伏期，具有协同效应。
2.受试药各组对实验性痴呆模型小鼠脑组织病理学变化的影响
组织病理学检查，各种随机取3份，各标本经10wt.％福尔马林固定、取材、脱水、浸蜡、包埋，再切成4μm厚切片，HE染色，200×光镜观察。结果如下：
代表性结果如图4所示。正常对照组细胞结构完整，排列规整；痴呆模型组细胞体缩小，着色变深，排列稀疏，散在细胞固缩、坏死；云芝多糖单用组3例取样中有2例海马区细胞核深染，核固缩，1例正常；银杏黄酮单用组3例取样中均有部分海马区细胞核深染，但程度较模型组轻；联合用药组3例取样中有1例部分海马区细胞核深染，程度较轻，其余2例均正常。
3.受试药各组对实验性痴呆模型小鼠脑组织胶质细胞原纤维酸性蛋白GFAP表达的影响
为了进一步在分子水平上分析各组受试药对痴呆模型小鼠的影响，我们采用免疫组化检测小鼠脑内胶质细胞原纤维酸性蛋白GFAP表达，并提取各组小鼠脑组织蛋白，采用Westernblot法检测GFAP的表达。
图5～7结果显示，与正常对照组比较，痴呆模型组小鼠脑内GFAP阳性染色细胞增多、染色较深(图5)且蛋白表达量较高(图6，图7)，GFAP的表达增加说明星形胶质细胞大量激活，而各给药组与模型组比较，GFAP阳性细胞数目不同程度减少、蛋白表达量也显著降低。
六、结论
云芝多糖和银杏黄酮联用对痴呆模型小鼠具有一定的增强记忆作用，联合用药组比单用组提升记忆的效果明显。
本发明实施例提供的增强痴呆模型小鼠记忆的方法，该方法采用云芝多糖与银杏黄酮联合经口给药，增加痴呆小鼠模型的记忆能力，云芝多糖中多糖含量为30wt.％，银杏黄酮中黄酮含量为25wt.％，云芝多糖与银杏黄酮联合用药时的用药剂量为：云芝多糖150mg/kg/d、银杏黄酮150mg/kg/d，云芝多糖与银杏黄酮联合用药时，可显著性缩短痴呆小鼠的逃避潜伏期、提高空间记忆能力、增加正确反应次数、延长首次犯错潜伏期、减少错误次数及减轻脑组织细胞状态异常及，并显著降低胶原纤维酸性蛋白GFAP的表达，同时云芝多糖与银杏黄酮联合经口给药对改善痴呆模型小鼠的记忆存在协同作用。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。
Claims (2)
1.云芝多糖和银杏黄酮的质量比为1:1的组合物在制备治疗阿兹海默症药物中的应用。
2.云芝多糖和银杏黄酮的质量比为1:1的组合物在制备增强记忆药物中的应用。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410264474.7A CN104082659B (zh) | 2014-06-13 | 2014-06-13 | 增强记忆的组合物及其应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410264474.7A CN104082659B (zh) | 2014-06-13 | 2014-06-13 | 增强记忆的组合物及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104082659A CN104082659A (zh) | 2014-10-08 |
| CN104082659B true CN104082659B (zh) | 2016-10-05 |
Family
ID=51630508
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410264474.7A Active CN104082659B (zh) | 2014-06-13 | 2014-06-13 | 增强记忆的组合物及其应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104082659B (zh) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1452972A (zh) * | 2003-05-23 | 2003-11-05 | 李森青 | 一种含银杏黄酮的植物提取物组合物及其用途 |
| CN1714832A (zh) * | 2005-07-11 | 2006-01-04 | 深圳市生物谷科技有限公司 | 具有协同作用的药物组合物 |
| CN101432008A (zh) * | 2006-04-28 | 2009-05-13 | 株式会社柳柳制药 | 具有对阿尔茨海默病和帕金森病的预防或治疗有用的新组合的银杏叶提取物及其提取和纯化方法 |
| CN103006718A (zh) * | 2012-12-18 | 2013-04-03 | 南京林业大学 | 一种有效降解血脂的组合物 |
| CN103404658A (zh) * | 2013-08-06 | 2013-11-27 | 北京绿源求证科技发展有限责任公司 | 一种养脑的食品养生茶冲剂 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000012102A1 (en) * | 1998-08-31 | 2000-03-09 | Proteotech, Inc. | Blended compositions for treatment of alzheimer's disease and other amyloidoses |
| KR100623164B1 (ko) * | 2004-07-22 | 2006-09-19 | 재단법인서울대학교산학협력재단 | 뇌신경 보호효과를 갖는 신규한 은행잎 엑스를 정제하는방법 및 이를 함유하는 조성물 |
-
2014
- 2014-06-13 CN CN201410264474.7A patent/CN104082659B/zh active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1452972A (zh) * | 2003-05-23 | 2003-11-05 | 李森青 | 一种含银杏黄酮的植物提取物组合物及其用途 |
| CN1714832A (zh) * | 2005-07-11 | 2006-01-04 | 深圳市生物谷科技有限公司 | 具有协同作用的药物组合物 |
| CN101432008A (zh) * | 2006-04-28 | 2009-05-13 | 株式会社柳柳制药 | 具有对阿尔茨海默病和帕金森病的预防或治疗有用的新组合的银杏叶提取物及其提取和纯化方法 |
| CN103006718A (zh) * | 2012-12-18 | 2013-04-03 | 南京林业大学 | 一种有效降解血脂的组合物 |
| CN103404658A (zh) * | 2013-08-06 | 2013-11-27 | 北京绿源求证科技发展有限责任公司 | 一种养脑的食品养生茶冲剂 |
Non-Patent Citations (1)
| Title |
|---|
| "天然药物防治老年痴呆";赵宁红;《医药导报》;20051231;第24卷(第12期);第1141-1142页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104082659A (zh) | 2014-10-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Spatz et al. | Overview of the potential role of Malassezia in gut health and disease | |
| Martin et al. | Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents | |
| Lei et al. | In vivo investigation on the potential of galangin, kaempferol and myricetin for protection of D-galactose-induced cognitive impairment | |
| Zhang et al. | Coeloglossum viride var. bracteatum extract attenuates D-galactose and NaNO2 induced memory impairment in mice | |
| Lu et al. | Neuroprotective effects of 20 (S)‐protopanaxatriol (PPT) on scopolamine‐induced cognitive deficits in mice | |
| Crews | Alcohol-related neurodegeneration and recovery: mechanisms from animal models | |
| Zhang et al. | Neuroprotective effect of Astragalus polysacharin on streptozotocin (STZ)-induced diabetic rats | |
| Yasueda et al. | Sanguisorba officinalis L. derived from herbal medicine prevents intestinal inflammation by inducing autophagy in macrophages | |
| CN102078460A (zh) | 一种防治阿尔茨海默病的中药及其制备方法 | |
| Lu et al. | Eleutheroside E attenuates isoflurane-induced cognitive dysfunction by regulating the α7-nAChR–NMDAR pathway | |
| Yang et al. | Electroacupuncture at GV24 and bilateral GB13 improves cognitive ability via influences the levels of Aβ, p-tau (s396) and p-tau (s404) in the hippocampus of Alzheimer’s disease model rats | |
| Yao et al. | Armillaria mellea fermentation liquor ameliorates p‐chlorophenylalanine‐induced insomnia associated with the modulation of serotonergic system and gut microbiota in rats | |
| Tan et al. | Effect of Chaihu Shugan Powder‐Contained Serum on Glutamate‐Induced Autophagy of Interstitial Cells of Cajal in the Rat Gastric Antrum | |
| Heni et al. | Ectopic fat accumulation in human astrocytes impairs insulin action | |
| Han et al. | Effects of radix polygalae on cognitive decline and depression in estradiol depletion mouse model of menopause | |
| Bian et al. | Nardosinone regulates the slc38a2 gene to alleviate Parkinson's symptoms in rats through the GABAergic synaptic and cAMP pathways | |
| Liu et al. | Liuwei Dihuang Decoction alleviates cognitive dysfunction in mice with D-galactose-induced aging by regulating lipid metabolism and oxidative stress via the microbiota-gut-brain axis | |
| Zou et al. | Dietary inulin alleviated constipation induced depression and anxiety-like behaviors: Involvement of gut microbiota and microbial metabolite short-chain fatty acid | |
| Li et al. | The hepatoprotective effect of Haoqin Qingdan decoction against liver injury induced by a chemotherapeutic drug cyclophosphamide | |
| Ling et al. | YINDARA-4 relieves visceral hypersensitivity in irritable bowel syndrome rats via regulation of gut microbiota and serotonin levels | |
| CN104082659B (zh) | 增强记忆的组合物及其应用 | |
| Feng et al. | Neural plasticity occurs in the adrenal medulla of asthmatic rats | |
| Cerantola et al. | Influence of Tilia tomentosa Moench extract on mouse small intestine neuromuscular contractility | |
| Zhang et al. | Paeoniflorin protects 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced Parkinson’s disease mice by inhibiting oxidative stress and neuronal apoptosis through activating the Nrf2/HO-1 signaling pathway | |
| Zhang et al. | The Effect and Mechanism of Sancao Lichang Decoction on Diarrhea-Predominant Irritable Bowel Syndrome by Regulating Tlr4/Myd88/Nf-b Pathway |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20141008 Assignee: SHAANXI YANGXIAN ZHIJIAN PHARMACEUTICAL TECHNOLOGY Co.,Ltd. Assignor: NANJING FORESTRY University Contract record no.: X2020320000277 Denomination of invention: Memory enhancing composition and its application Granted publication date: 20161005 License type: Common License Record date: 20201127 |
|
| EE01 | Entry into force of recordation of patent licensing contract |