五味子有效成分分离纯化及对记忆障碍模型小鼠学习记忆的影响
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摘要
学习和记忆是人类大脑的主要功能之一，是哺乳动物大脑的高级神经生理活动。然而，随着年龄的不断增长，学习和记忆能力的下降是伴随着年龄增长而出现的一种常见现象。生活条件的改善、老年人口的比例增加，将会有越来越多的人受到学习和记忆能力下降症状的困扰。因此，早期预防和治疗这种症状是目前研究的热点之一，具有非常广阔的市场前景。目前常用的药物包括自由基清除药、防止β-淀粉蛋白沉积药、M受体激动药和胆碱酯酶抑制剂等。这些药物或由于其较大的副作用，或由于昂贵的价格使其应用受到限制。中国传统的中草药由于其较低的毒副作用和明确的疗效，而成为人们研究与开发改善学习、记忆能力药物的研究热点。
五味子（Schisandra）是我国传统中药，传统中医认为五味子有镇静安神、止咳平喘、滋补强健和保肝护肝等作用。中华人民共和国药典（2010）收录有两种五味子药材，分别为北五味子（Schisandra chinensis (Turcz) Baill）和南五味子（Schisandra Sphenanthera）的成熟果实。北五味子又名五味子，主产于东北，内蒙古等地，其药用成分高、疗效显著而著称，优于南五味子。在上千年的中医临床应用中，主要用于治疗久嗽虚喘、心悸、失眠、久泻不止、自汗、短气脉虚、内热消渴、津伤口渴、遗尿尿频、梦遗滑精、盗汗等症。五味子有效成分主要包括木脂素、多糖，挥发油、有机酸、脂肪油、氨基酸、色素、靴质等多种成分。目前为止，共分离鉴定出200余个化合物，其中含量较高、研究较多、较深入且应用较广泛的主要成分为木脂素，约150多种，其次为多糖和挥发油。五味子的药理作用涉及中枢神经系统、心血管系统、消化系统、生殖系统以及泌尿系统等各个方面。五味子中主要成分对中枢神经系统具有改善学习、记忆，镇静、催眠，抗衰老和镇痛等作用。
本研究以传统中药材五味子为研究对象，利用现代分离纯化技术制备五味子总木脂素、五味子醇甲、五味子乙素、五味子多糖等活性成分，在整体上，以小鼠为试验对象，采用急性腹腔注射东莨菪碱建立记忆获得性障碍的拟痴呆动物模型，探讨五味子总木脂素、五味子多糖对东蓑若碱所致拟痴呆大鼠学习记忆行为学、自由基代谢、胆碱能神经递质和单胺类神经递质水平的影响。在分子上，以大鼠海马神经元HT22细胞为试验对象，用MTT、免疫荧光技术、流式细胞仪及Western blot等方法，研究五味子醇甲、五味子乙素的抑制细胞凋亡，保护神经细胞的作用。系统的研究了五味子提取物对东蓑若碱所致拟痴呆大鼠的学习记忆改善作用及其作用机制，为将其开发为新的抗痴呆药物提供一定理论依据。
1．通过正交试验法筛选出五味子木脂素的最佳提取工艺为：乙醇浓度为90%，料液比为10倍，超声提取时间30min，提取3次。通过柱层析法分离得6个五味子木脂素类化合物，分别为五味子醇甲、五味子醇乙、五味子酯甲、五味子甲素、五味子乙素和五味子丙素。
2．通过正交试验法筛选五味子多糖提取及纯化最佳工艺。最佳提取工艺为：料液比为1:10，蒸馏水提取3次，提取温度90℃，每次1h。最佳醇沉条件为：乙醇浓度90%，醇沉体积3倍，醇沉3次。采用H2O2脱色法，最佳脱色条件为：H2O2用量为4%，脱色时间120min，脱色温度45℃，溶液pH为7.0。采用酶法脱蛋白，最佳脱蛋白条件为：木瓜蛋白酶用量120IU/ml，pH5.5，酶解温度40℃，酶解时间60min。
3．Morris水迷宫法测试五味子总木脂素和多糖对东蓑若碱所致痴呆小鼠学习、记忆能力的影响。给予模型动物五味子总木脂素后，可以明显缩短寻其找平台的潜伏期、寻找平台的路径、增加第Ⅲ象限停留时间、第Ⅲ象限路程百分比和穿台次数。实验结果表明五味子总木脂素可以改善腹腔注射东莨菪碱使小鼠产生学习记忆障碍的症状，对东莨菪碱所致拟痴呆小鼠学习记忆获得性障碍有治疗的作用。而五味子多糖无此效果。
4．通过检测总木脂素和多糖对模型小鼠脑组织中自由基代谢及单胺类递质含量的影响，初步阐明其作用机制。五味子总木质素可以提高小鼠血液及脑组织中SOD和T-AOC活性，明显降低MDA、NO含量；升高ChAT的含量，而对AChE含量无明显影响。同时，可以可以显著降低模型小鼠脑组织NE,DA的含量，升高5-HT的含量。而给予五味子多糖后，对上述指标无明显影响。实验结果表明，五味子总木脂素一方面，可通过提高机体清除自由基的能力、降低脂质过氧化损伤程度、保护脑组织，减轻自由基对脑组局部的损害；另一方面，学习记忆能力的改善也与模型小鼠脑组织中单胺类递质含量的改变有关。
5．通过体外实验探讨了分离出的五味子醇甲、五味子乙素和五味子多糖对海马神经元HT22细胞的保护作用及可能的机制。五味子醇甲，五味子乙素各剂量组可不同程度的提高细胞对MTT的摄取能力，使HT22细胞活力增加，并且对H2O2诱导的海马神经元HT22细胞损伤有保护的作用，并且抑制HT22细胞凋亡，上调bcl-2蛋白，下调bαx蛋白，下调Caspase-3蛋白。而给予五味子多糖处理后，对上述指标无明显影响。实验结果表明，五味子醇甲、五味子乙素对HT22细胞的保护作用与其抗凋亡作用有关。
Learning and memory are the main functions of human brain, the seniorphysiological activities of mammals. However, with the increase of ages, the declineof learning and memory is the common phenomenon. The improvement of livingstandard and increase of the aging people, more and more people will be perplexed bythe decline of learning and memory. The early precautions and remedy of thesymptom become the hot issue and have broad market prospects. At present, thecommon drugs including Free radical scavenger, Prevent β-amyloid depositionmedicine, M receptor agonist, cholinesterase inhibitors, etc. But the application isrestricted because of the side-effects and high price. Due to the low toxicity andcurative effect, the Chinese herbal medicines have become the hopspots inresearching and developing of the medicines for learning and memory.
Schisandra chinensis (Turcz.) Baill. is a famous medicinal drug in TraditionalChinese Medicine. It’s friuts has been used for centuries as an antitussive, tonic andsedative agent, and in traditional medicine to improve the liver function of patientswith viral hepatitis. There were two different crude drugs have been included in theChinese Pharmacopoeia, Schisandrae chinensis Fructus and Schisandraesphenantherae Fructus, respectively. Schisandrae chinensis Fructus is well known aswuweizi, it is distributed in Jilin, Liaoning, Heilongjiang, and Neimenggu provincesin China, as well as in Russia, Japan and Korea. Schisandrae chinensis Fructus iscommonly used for the treatment of spermatorrhea, night sweating, protracteddiarrhea, nocturnal emission, spontaneous sweating, frequent urination, shortness ofbreath and feeble pulse, enuresis, chronic cough and dyspnea, diabetes, wasting-thirst,palpitation, impairment of bodyfluids with thirst, and has been considered of betterquality than Schisandrae sphenantherae Fructus in traditional Chinese medicine. Inrecent years, with in-depth study of chemical composition and pharmacological effects of Schisandrae chinensis Fructus, the pharmacological activity and traditionalapplication of active ingredients of Schisandrae chinensis Fructus was clarified. Inorder to more reasonable and effective use of this traditional drug, we isolate andpurify the bioactive components from Schisandrae Chinensis Fructus, and study theimprove memory function of those components systematacially and in depth.
1. According to the orthogonal experimental design, the optimum conditions ofextracting lignans from the Schisandrae chinensis Fructus was showed as following:ethanol concentration was90%, liquid-solid ratio was10:1, supersonic extractingtime was30min and extracting three times.
2. According to the orthogonal experimental design, the optimum conditions ofextracting and Purification polysaccharide from the Schisandrae chinensis Fructuswas found. The optimum conditions of extracting polysaccharide was showed asfollowing: liquid-solid ratio was10:1, extracting solvent was water, extractingtemperature was90℃, extracting time was1h and extracting three times. Theoptimum conditions of alcohol precipitation was showed as following: ethanolconcentration was90%, liquid-solid ratio was3:1and repeat3times. The optimumconditions of decoloration was showed as following: liquid-solid ratio was4:100,decolor temperature was45℃, pH7.0, decolor time was2h. The optimumconditions of deproteinization was showed as following: papain was120IU/ml, pH5.5,deproteinize temperature was40℃and deproteinizetime was60min.
3. To research the improvement of SCL and SCP in the memory acquisitionimpairment of mice induced by scopolamine of the Morris. Memory acquisitionimpairment model in mice with the method of scopolamine intraperitoneal injectionmade, the improvement of SCL in the memory acquisition impairment of miceobserved by means of Morris. SCL could shorten the incubation period reduce thenumber of errors in the water maze test. SCL have the improvement in the memoryacquisition impairment of mice induced by scopolamine. SCP have not.
4. Using square water maze to investigate the ability of the learning and memoryof mice, the content of ChAT, AchE in the brain tissues, SOD in both brain tissuesand serum and MDA in the both serum and liver tissues were determined，respectively.The concent of ChAT and SOD increased significantly. The AchE and MDA content in the brain tissues dec reased.
5. To explore the protective effects and mechanisms of SA, SB and SCP on thehippo-nerve HT22by external test. The SA and SB groups may enhance the MTTabsorbing of cells, increase the activity of HT22, protect the HT22damage induced byH2O2, and restrain the apoptosis of HT22, up-regulate bcl-2, down-regulate bax andCaspase-3. The handled SCP has no significant effect on the above index. The resultsshow that SA, SB and SCP are related to the protective and anti-apoptosis effects ofHT22.
五味子（Schisandra）是我国传统中药，传统中医认为五味子有镇静安神、止咳平喘、滋补强健和保肝护肝等作用。中华人民共和国药典（2010）收录有两种五味子药材，分别为北五味子（Schisandra chinensis (Turcz) Baill）和南五味子（Schisandra Sphenanthera）的成熟果实。北五味子又名五味子，主产于东北，内蒙古等地，其药用成分高、疗效显著而著称，优于南五味子。在上千年的中医临床应用中，主要用于治疗久嗽虚喘、心悸、失眠、久泻不止、自汗、短气脉虚、内热消渴、津伤口渴、遗尿尿频、梦遗滑精、盗汗等症。五味子有效成分主要包括木脂素、多糖，挥发油、有机酸、脂肪油、氨基酸、色素、靴质等多种成分。目前为止，共分离鉴定出200余个化合物，其中含量较高、研究较多、较深入且应用较广泛的主要成分为木脂素，约150多种，其次为多糖和挥发油。五味子的药理作用涉及中枢神经系统、心血管系统、消化系统、生殖系统以及泌尿系统等各个方面。五味子中主要成分对中枢神经系统具有改善学习、记忆，镇静、催眠，抗衰老和镇痛等作用。
本研究以传统中药材五味子为研究对象，利用现代分离纯化技术制备五味子总木脂素、五味子醇甲、五味子乙素、五味子多糖等活性成分，在整体上，以小鼠为试验对象，采用急性腹腔注射东莨菪碱建立记忆获得性障碍的拟痴呆动物模型，探讨五味子总木脂素、五味子多糖对东蓑若碱所致拟痴呆大鼠学习记忆行为学、自由基代谢、胆碱能神经递质和单胺类神经递质水平的影响。在分子上，以大鼠海马神经元HT22细胞为试验对象，用MTT、免疫荧光技术、流式细胞仪及Western blot等方法，研究五味子醇甲、五味子乙素的抑制细胞凋亡，保护神经细胞的作用。系统的研究了五味子提取物对东蓑若碱所致拟痴呆大鼠的学习记忆改善作用及其作用机制，为将其开发为新的抗痴呆药物提供一定理论依据。
1．通过正交试验法筛选出五味子木脂素的最佳提取工艺为：乙醇浓度为90%，料液比为10倍，超声提取时间30min，提取3次。通过柱层析法分离得6个五味子木脂素类化合物，分别为五味子醇甲、五味子醇乙、五味子酯甲、五味子甲素、五味子乙素和五味子丙素。
2．通过正交试验法筛选五味子多糖提取及纯化最佳工艺。最佳提取工艺为：料液比为1:10，蒸馏水提取3次，提取温度90℃，每次1h。最佳醇沉条件为：乙醇浓度90%，醇沉体积3倍，醇沉3次。采用H2O2脱色法，最佳脱色条件为：H2O2用量为4%，脱色时间120min，脱色温度45℃，溶液pH为7.0。采用酶法脱蛋白，最佳脱蛋白条件为：木瓜蛋白酶用量120IU/ml，pH5.5，酶解温度40℃，酶解时间60min。
3．Morris水迷宫法测试五味子总木脂素和多糖对东蓑若碱所致痴呆小鼠学习、记忆能力的影响。给予模型动物五味子总木脂素后，可以明显缩短寻其找平台的潜伏期、寻找平台的路径、增加第Ⅲ象限停留时间、第Ⅲ象限路程百分比和穿台次数。实验结果表明五味子总木脂素可以改善腹腔注射东莨菪碱使小鼠产生学习记忆障碍的症状，对东莨菪碱所致拟痴呆小鼠学习记忆获得性障碍有治疗的作用。而五味子多糖无此效果。
4．通过检测总木脂素和多糖对模型小鼠脑组织中自由基代谢及单胺类递质含量的影响，初步阐明其作用机制。五味子总木质素可以提高小鼠血液及脑组织中SOD和T-AOC活性，明显降低MDA、NO含量；升高ChAT的含量，而对AChE含量无明显影响。同时，可以可以显著降低模型小鼠脑组织NE,DA的含量，升高5-HT的含量。而给予五味子多糖后，对上述指标无明显影响。实验结果表明，五味子总木脂素一方面，可通过提高机体清除自由基的能力、降低脂质过氧化损伤程度、保护脑组织，减轻自由基对脑组局部的损害；另一方面，学习记忆能力的改善也与模型小鼠脑组织中单胺类递质含量的改变有关。
5．通过体外实验探讨了分离出的五味子醇甲、五味子乙素和五味子多糖对海马神经元HT22细胞的保护作用及可能的机制。五味子醇甲，五味子乙素各剂量组可不同程度的提高细胞对MTT的摄取能力，使HT22细胞活力增加，并且对H2O2诱导的海马神经元HT22细胞损伤有保护的作用，并且抑制HT22细胞凋亡，上调bcl-2蛋白，下调bαx蛋白，下调Caspase-3蛋白。而给予五味子多糖处理后，对上述指标无明显影响。实验结果表明，五味子醇甲、五味子乙素对HT22细胞的保护作用与其抗凋亡作用有关。
Learning and memory are the main functions of human brain, the seniorphysiological activities of mammals. However, with the increase of ages, the declineof learning and memory is the common phenomenon. The improvement of livingstandard and increase of the aging people, more and more people will be perplexed bythe decline of learning and memory. The early precautions and remedy of thesymptom become the hot issue and have broad market prospects. At present, thecommon drugs including Free radical scavenger, Prevent β-amyloid depositionmedicine, M receptor agonist, cholinesterase inhibitors, etc. But the application isrestricted because of the side-effects and high price. Due to the low toxicity andcurative effect, the Chinese herbal medicines have become the hopspots inresearching and developing of the medicines for learning and memory.
Schisandra chinensis (Turcz.) Baill. is a famous medicinal drug in TraditionalChinese Medicine. It’s friuts has been used for centuries as an antitussive, tonic andsedative agent, and in traditional medicine to improve the liver function of patientswith viral hepatitis. There were two different crude drugs have been included in theChinese Pharmacopoeia, Schisandrae chinensis Fructus and Schisandraesphenantherae Fructus, respectively. Schisandrae chinensis Fructus is well known aswuweizi, it is distributed in Jilin, Liaoning, Heilongjiang, and Neimenggu provincesin China, as well as in Russia, Japan and Korea. Schisandrae chinensis Fructus iscommonly used for the treatment of spermatorrhea, night sweating, protracteddiarrhea, nocturnal emission, spontaneous sweating, frequent urination, shortness ofbreath and feeble pulse, enuresis, chronic cough and dyspnea, diabetes, wasting-thirst,palpitation, impairment of bodyfluids with thirst, and has been considered of betterquality than Schisandrae sphenantherae Fructus in traditional Chinese medicine. Inrecent years, with in-depth study of chemical composition and pharmacological effects of Schisandrae chinensis Fructus, the pharmacological activity and traditionalapplication of active ingredients of Schisandrae chinensis Fructus was clarified. Inorder to more reasonable and effective use of this traditional drug, we isolate andpurify the bioactive components from Schisandrae Chinensis Fructus, and study theimprove memory function of those components systematacially and in depth.
1. According to the orthogonal experimental design, the optimum conditions ofextracting lignans from the Schisandrae chinensis Fructus was showed as following:ethanol concentration was90%, liquid-solid ratio was10:1, supersonic extractingtime was30min and extracting three times.
2. According to the orthogonal experimental design, the optimum conditions ofextracting and Purification polysaccharide from the Schisandrae chinensis Fructuswas found. The optimum conditions of extracting polysaccharide was showed asfollowing: liquid-solid ratio was10:1, extracting solvent was water, extractingtemperature was90℃, extracting time was1h and extracting three times. Theoptimum conditions of alcohol precipitation was showed as following: ethanolconcentration was90%, liquid-solid ratio was3:1and repeat3times. The optimumconditions of decoloration was showed as following: liquid-solid ratio was4:100,decolor temperature was45℃, pH7.0, decolor time was2h. The optimumconditions of deproteinization was showed as following: papain was120IU/ml, pH5.5,deproteinize temperature was40℃and deproteinizetime was60min.
3. To research the improvement of SCL and SCP in the memory acquisitionimpairment of mice induced by scopolamine of the Morris. Memory acquisitionimpairment model in mice with the method of scopolamine intraperitoneal injectionmade, the improvement of SCL in the memory acquisition impairment of miceobserved by means of Morris. SCL could shorten the incubation period reduce thenumber of errors in the water maze test. SCL have the improvement in the memoryacquisition impairment of mice induced by scopolamine. SCP have not.
4. Using square water maze to investigate the ability of the learning and memoryof mice, the content of ChAT, AchE in the brain tissues, SOD in both brain tissuesand serum and MDA in the both serum and liver tissues were determined，respectively.The concent of ChAT and SOD increased significantly. The AchE and MDA content in the brain tissues dec reased.
5. To explore the protective effects and mechanisms of SA, SB and SCP on thehippo-nerve HT22by external test. The SA and SB groups may enhance the MTTabsorbing of cells, increase the activity of HT22, protect the HT22damage induced byH2O2, and restrain the apoptosis of HT22, up-regulate bcl-2, down-regulate bax andCaspase-3. The handled SCP has no significant effect on the above index. The resultsshow that SA, SB and SCP are related to the protective and anti-apoptosis effects ofHT22.
引文
[1]RD Haworth. The chemistry of the lignan group of natural products [J]. J Chem Soc,1942:448-456N K Kochetkov. Tetrahedron Lett,1961:730-732.
[2]高建平.五味子南五味子基源植物的比较研究[D].上海：复旦大学药学院,2003.
[2]陈道峰,王彦涵,高建平等.植物化学分类学(周荣汉)[M].上海：上海科技出版社,2005：451-452.
[3]陈延镛,舒增宝,黎莲娘等.北五味子的研究-北五味子降谷丙转氨酶有效成分的分离和鉴定[J].中国科学,1976,(1)：98-99.
[4]陈延铺,黎莲娘.北五味子的研究-五味子酯甲和五味子酯乙的化学结构测定[J].化学学报,1976,(34)：45-46.
[5]宋万志,童玉懿.五味子属植物木脂素类资源的研究[J].天然产物研究与开发,1990,2(4)：51-58.
[6]汤臣康.五味子的化学和药理研究的新进展[J].西北药学杂志,1994,9(16)：278-282.
[7]宋万志.五味子科植物的木脂素类成分及生物活性与国内资源[J].天然产物研究与开发,1991,3(1)：68-80.
[8]谢蓝.五味子类木脂素的化学研究进展[J].中国药物化学杂志,1992,2(2)：65-80.
[9]JS Liu, SD Fang, MF Huang, et al. Structure on the Active Principles of Schisandra sphenanthera Rehd.et Walls [J]. Sci Sin,1978,21(4):483-502.
[10]Y Ikeya, T Teihachiro, Y Itiro. The Constituents of Schisandra chinensis Ball.ⅩⅡ.Is-olation and Structure of a New Lignan Gomisin R the Absolute Structure of Wuweizisu C and Isolation of Schisantherin D [J]. Chem Pharm Bull,1982,30(9):3207-3211.
[11]Y Ikeya, T Teihachiro, Y Itiro. The Constituents of Schisandra chinensis Ball.I.Isolat-ion and Structure Determination of Five New Lignans Gomisin A B C F and G and the Absolute Structure of Schizandrin [J]. Chem Pharm Bull1979,27(6):1383-1394.
[12]Y Ikeya, T Teihachiro, Y Itiro. The Constituents of Schisandra chinensis Ball.The Cleavage of the Methylenedioxy Moiety Lead Tetraacetate in Benzene and the Structrure of Angeloylgomisin Q [J]. Chem Pharm Bull,1979,27(10):2536-2538.
[13]刘嘉森,黄梅芬.华中五味子的研究Ⅳ安五酸和d1-安五脂素的结构及d-表加巴辛的绝对构型[J].化学学报,1984,42(3)：264-270.
[14]Yang XW, Miyashiro H, Hattori M,Namba T, et al. Isolation of novel lignans, heteroclitins F and G, from the stems of Kadsura heteroclita, and anti-lipid peroxidative actions of heteroclitins A-G and related compounds in the in vitro rat liver homogenate system [J]. Chem Pharm Bull,1992,40(6):1510-1516.
[15]Matsushima Y, Amemiya R, Liu JS, et al. Directcurrent therapy with chemotherapy for the local control of lung cancer [J]. Nippon Gan Chiryo Gakkai Shi,1989,24(10):2341-2348.
[16]Takani M, Ohya K, Takahashi K, et al. Studies on constituents of medicinal plants XXII Constituents of Schizandra nigra Max [J]. Chem Pharm Bull,1979,27(6):1422-1425.
[17]Wang HJ, Chen YY, Liang XT, et al. The structure of a new lignin diol [J]. Chinese Chemical Letters,1993,4(1):31-32.
[18]Ademar A, Silva F, Sergio A, et al. Tetrahydrofuran Lignans from Nectandra megapotamica with Trypanocidal Activity [J]. J Nat Prod,2004,67(1):42-45.
[19]Chen H, Zhang M, Qu Z, et al. Antioxidant activities of different fractions of polysaccharide conjugates from green tea (Camellia sinensis)[J]. Food Chemistry,2008,10(6):559-563.
[20]Jiang YH, Jiang XL, Wang P, et al. The antitumor and antioxidative activities of polysaccharides isolated from Isaria farinosa B05[J]. Microbiological Research,2008,16(3):424-430.
[21]Yuan JF, Zhang ZQ,Fan ZC, et al. Antioxidant effects and cytotoxicity of three purified polysaccharides from Ligusticum chuanxiong Hort [J]. Carbohydrate Polymers,2008,(74):822-827.
[22]Chi AP, Chen JP, Wang ZZ, et al. Morphological and structural characterization of a polysaccharidefrom Gynostemma pentaphyllum Makino and its anti-exercise fatigue activity [J]. Carbohydrate Polymers,2008,(74):868-874.
[23]Arumugam S, Hanumantha RBR, Periasamy S, et al. Anti-peroxidative and anti-hyperlipidemic nature of Ulva lactuca crude polysaccharide on D-Galactosamine induced hepatitis in rats [J]. Food and Chemical Toxicology,2008,(46):3262-3267.
[24]徐世枕,王彩霞,李广全等.北五味子粗多糖的提取与成分分析[J].中国药物化学杂志,1992,2(1)：44-48.
[25]姜波,孙静,刘春等.五味子水溶性多糖提取及纯化工艺的优化[J].时珍国医国药,2009,20(10)：2614-2616.
[26]孟宪军,那广宁,高晓旭等.北五味子多糖的分离纯化研究[J].食品科技,2008,33(11)：197-199.
[27]张胜娜,吴素香.南北五味子挥发油化学成分及药理作用研究进展[J].中药材,2007,30(1)：118-120.
[28]戴好富,谭宁华,周俊等.北五味子挥发性化学成分研究[J].中草药,2005,6(9)：1309-1310.
[29]谷昊,张兰杰,辛广.北五味子叶挥发油化学成分分析[J].鞍山师范学院学报,2009,11(2)：38-41.
[30]孙广仁,杨文胜滕,玉辉等.五味子茎皮挥发油的化学成分研究[J].吉林林学院学报,1991,7(3)：18-21.
[31]李斌,李元甦,孟宪军等.超临界C02萃取北五味子藤茎挥发油的GC-MS分析[J].食品工业科技,2001,32(2)：106-108.
[32]李晓宁,崔卉,宋又群.辽五味子果实挥发油成分的鉴定[J].药学学报,2001,36(3)：215-219.
[33]王炎,王进福,尤宏.北五味子种子挥发油的GC/MS分析[J].中国药学杂志,2001,36(2)：91-92.
[34]刘亚敏,刘玉民,李鹏霞.超临界CO2流体萃取-GC-MS分析南北五味子挥发油成分[J].食品科学,2011,32(6)：204-208.
[35]林伟卓,陈玉海.北五味子全氮及氨基酸含量测定[J].特产研究,1998,(1)：35-36.
[36]王丽薇,周长新, Bernd Schneider等.‘北五味子化学成分研究[J].中国现代应用药学杂志,2006,23(5)：363-365.
[37]官艳丽,曹沛,郁开北.北五味子化学成分的研究[J].中草药,2006,37(2)：185-187.
[38]汪有初,周俊,谭宁华.五味子的环二肽及其合成[J].药学学报,1999,34(1)：19-22.
[39]Hu D, Li C, Han N, Miao L, et al. Deoxyschizandrin isolated from the fruits of Schisandra chinensis ameliorates Aβ1-42-induced memory impairment in mice [J].Planta Med.2012,78(12):1332-1336.
[40]Giridharan W, Thandavarayan RA, Sato S, et al. Prevention of scopolamine-induced memory deficits by schisandrin B, an antioxidant lignan from Schisandra chinensis in mice [J]. Free Radic Res.2011,45(8):950-9588.
[41]王艳春,任旷,范红艳.五味子总素对记忆障碍模型小鼠学习记忆的改善作用[J].中国中药杂志,2011,36(23)：3310-3313.
[42]王艳春,任旷,范红艳.五味子醇甲对记忆障碍模型小鼠学习记忆的影响[J].中国药学杂志,2011,46(14)：1097-1103.
[43]于方,拓西平,吕建勇等.华中五味子酮对阿尔茨海默病样大鼠学习记忆功能及海马区核因子κB、诱导型一氧化氮合酶表达的影响[J].第二军医大学学报,2007,28(12)：1351-1355.
[44]李楚华,肖鹏,欧阳效等.益智Ⅱ号促进小鼠记忆保持的观察与分析[J].华南师范大学学报(自然科学版),2004,(1)：112-116.
[45]Yang JM, Lp PS, Che CT, et al. Relaxant effects of Schisandra chinensis and its major lignans on agonists-induced contraction in guinea pig ileum. Phytomedicine [J],2011,18(13):1153-1160.
[246]霍艳双,陈晓辉,李康.北五味子的镇静、催眠作用[J].沈阳药科大学学报,2005,25(2)：126-128.
[47]张林魁,钮心懿.五味子醇甲对中枢神经系统单胺类递质的影响[J].中国 医学科学研学报,1991,13(1)：13-16.
JS, L HK, D NT. Liganswith inhibitory activity NFAT transcription from Schisandra Chinenisis [J]. Plant a Medica,2003,69(1):63-64.
[249]齐治,崔景荣,田建柱等.五味子果实挥发油对中枢神经系统的药理作用研究[J].北京医科大学学报,1988,20(6)：457-412.
[50]Chen Y, Tang J, Wang X, et al. An immunostimulatory polysaccharide (SCP-IIa) from the fruit of Schisandra chinensis (Turcz.) Baill. Int J Biol Macromol [J].2012,50(3):844-848.
[251]孙文娟,吕文伟,于晓凤.北五味子粗多糖抗衰老作用的实验研究[J].中国老年学杂志,2001,11(21)：454-455.
[52]苗明三.五味子多糖对衰老模型小鼠的影响[J].中国医药学报,2002,17(3)：187-188.
[53]门红军,刘立.北五味子粗多糖对大鼠自由基代谢的影响[J].吉林中医药,2003,23(7)：48.
[54]刘晓瑞.北五味子抗衰老作用的实验研究[J].中国老年学杂志,2005,25(12)：1562.
[55]辛晓林,张桂春,黄清荣.五味子镇痛效果研究[J].安徽农业科学,2009,37(32)：15842-15843.
[56]刘丹娜,罗晶.不同剂量五味子多糖灌胃给药镇痛作用的观察[J].第四军医大学学报,2008,29(12)：1115-1117.
[57]李庆耀,孙全忠,陈道峰等.两种南五味子属药用植物油性成分的镇痛作用[J].上海医科大学学报,1999,26(1)：56.
[58]孙侃.北五味子对蛙心强心作用的初步观察[J].新医学,1972,(6)：33-35.
[59]刘菊秀,陈静,苗戎等.北五味子对心脏电活动及收缩力的影响[J].中草药,1999,30(4)：280-281.
[60]刘菊秀,苗戎,陈静等.五味子对心肌力学和心率的影响[J].中草药,1999,30(2)：122-124.
[61]曾祥国,许志奇,彭国瑞等.五味子对家兔心血管酶组化的药理作用研究 [J].四川中医,1990,(4)：10-12.
[62]映红,李湘楚,罗德生.五味子提取液对动物缺氧及心肌缺血的保护作用[J].咸宁医学院学报,1998,12(2)：79-82.
[63]Park JY, Choi YW, Yun JW. Gomisin J from Schisandra chinensis induces vascular relaxation via activation of endothelial nitric oxide synthase [J]. Vascul Pharmacol.2012,57(2-4):124-130.
[64]Park JY, Shin HK, Lee YJ, et al. The mechanism of vasorelaxation induced by Schisandra chinensis extract in rat thoracic aorta [J]. J Ethnopharmacol,2009,121(1):69-73.
[265]李庆耀,陈道峰,江明华.戈米辛J和异型南五味子丁素对大鼠胸主动脉的作用[J].上海医科大学学报,1999,26(4)：280-282.
[66]蒋仕丽,章蕴毅,陈道峰.异型南五味子丁素、五味子酚和(+)-安五脂素对血小板聚集的影响[J].复旦学报,2005,32(4)：467-470.
[67]林童俊.五味子酚和丹酚酸A抗氧化作用机理及对阿霉素心脏毒性的保护作用[J].生理科学进展,1991,22(4)：342-345.
[68]刘扬,徐广智,林童俊等.五味子酚对AQ损伤心肌药理作用的ESR研究[J].科学通报,1993,38(19)：1809-1812.
[69]Zhu M, Yeung RY, Lin KF, et al. Improvement of phase I drug metabolism with Schisandra chinensis against CCl4hepatotoxicity in a rat model [J]. Planta Med,2000,66(6):521-5.
[70](Zhu M, Lin KF, Yeung RY, et al. Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4intoxication model [J]. J Ethnopharmacol,1999,67(1):61-68.
[71]齐彦,郭丽新,周迎春.五味子对四氯化碳所致小鼠急性肝损伤的作用研究[J].中医药学报,2009,37(4)：26-27.
[72]许珂玉,柳春.五味子多糖对CCl4诱导的肝损伤大鼠亚细胞水平的保护作用[J].中国老年学杂志,2011,31(8)：1352-1353.
[73]蔡绍先,陈玮莹,吴健谊等.五味子提取物对CC14中毒大鼠肝超微结构的保护作用[J].癌变、畸变、突变,2010,22(1)：52-54.
[74]陈玮莹,温博贵,郑瑞明等.五味子对CC14中毒大鼠肝细胞核基质蛋白和结构的保护作用[J].免疫学杂志,22(4)：455-459.
[75]蔡晶,黄巧冰,迟德彪.五味子乙素对H2O2损伤人肝细胞Fas通路的影响[J].南方医科大学学报,2012,32(4)：583-585.
[76]张锦楠,李亚伟,徐艳霞.甘草和五味子对大鼠肝微粒体CYP450诱导作用的研究[J].中国药学杂志,2002,37(6)：424-426.
[77]刘耕陶,包天桐,巍怀玲等.五味子乙素对对小鼠肝细胞微粒体细胞细胞色素P-450的诱导作用[J].药学学报,1980,15(4)：206-211.
[78]Iwata H, Tezuka Y, Usia T. Inhibition of human liver microsomal CYP3A4and CYP2D6by extracts from78herbal medicines [J]. J Tradit Med,2004,21:281
[79]Iwata H. Identification and characterization of potent CYP3A4inhibitors in schisandra fruit extract [J]. Drug Metab Dispos,2004,32:1351-1358.
[80]陈倩,吴育晶,程能能.五味子提取物对大鼠肝CYP3A酶的双重作用[J].药学学报,2010,45(9)：1194-1198.
[81]孙成仁,彭正松.北五味子的抑菌作用[J].四川师范学院学报,1993,14(3)：200-202.
[82]刘志春,王小丽.五味子等29种中草药的体外抑菌实验[J].赣南医学院学报,2004,24(5)：509-511.
[83]边才苗,杨云斌,费杰等.五味子提取物体外抑菌作用初探[J].浙江中医药大学学报,2009,33(1)：122-123.
[84]邹金美,陈芸,陈秀桥等.五味子提取物的抑菌活性研究[J].江苏农业科学,2011,39(5)：400-402.
[85]张锐利,包东东,刘华英.不同提取方法对北五味子提取物抑菌活性的影响[J].安徽农业科学,2010,38(24)：13177-13179.
[86]吴少辉,叶伟娟,赵婷等.南五味子乙醇提取物对食品腐败细菌的抑制活性研究[J].中国食品学报,2012,12(8)：104-109.
[87]李斌,孟宪军,薛雪等.北五味子乙素清除自由基及体外抑菌作用的研究[J].食品科学,2011,32(5)：79-82.
[88]许瑞波,高颖颖,万蓓蓓等.北五味子叶多糖的提取及抑菌活性[J].食品科学,2012,33(20)：33-37.
[89]Gnabre J, Unlu I, Chang TC, et al. Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: Structure-activity relationships [J]. J Chromatogr B Analyt Technol Biomed Life Sci.2010,878(28):2693-2700.
[90]Hwang D, Shin SY, Lee Y, et al. A compound isolated from Schisandra chinensis induces apoptosis [J]. Bioorg Med Chem let,2011,21(20):6054-6057.
[91]禹洁,刘培勋,龙伟.五味子总木脂素的分离纯化与体外抗肿瘤活性研究[J].中国药师,2009,12(12)：1718-1720.
[92]李玲,胡迅,潘铿荣等.五味子乙素对MRP介导的肿瘤多药耐药逆转作用的研究[J].同济大学学报,2006,27(6)：19-23.
[93]孙华,刘耕陶.五味子果仁醇提取物含药血清逆转肿瘤多药耐药及抑制耐药糖蛋白(P-gp)的作用[J].中国新药杂志,2009,18(12)：1130-1135.
[94]黄玲,陈玲,张振林.五味子多糖对荷瘤小鼠血液SOD和MDA的影响[J].福建中医学院学报,2005,15(1)：28-29.
[95]黄玲,陈玲,张振林.五味子多糖对荷瘤鼠瘤体抑制作用的病理学观察[J].中药材,2004,27(3)：202-203.
[96]Zhang M, Liu M, Xiong M, et al. Schisandra chinensis fruit extract attenuates albuminuria and protects podocyte integrity in a mouse model of streptozotocin-induced diabetic nephropathy [J]. J Ethnopharmacol,2012,141(1):111-118.
[95]安丽萍,王英平,刘晓梅等.五味子油对链脲佐菌素诱导的2型糖尿病大鼠的影响[J].中草药,2012,43(3)：552-556.
[96]柴可夫,覃志成,王亚丽.北五味子油对糖尿病小鼠胰岛细胞形态及功能的影响[J].中国中医药科技,2007,14(3)：177-178.
[99]安丽萍,王英平,王春梅等.五味子油对2型糖尿病大鼠胰岛B细胞凋亡的影响[J].2012,38(1)：84-88.
[100]刘馨,刘学政.五味子油对2型糖尿病胰岛素抵抗大鼠的作用及机制[J].中国生化药物杂志,2012,33(6)：800-802.
[101]刘苗,张勉之,谭小月.复方五味子醇提液对糖尿病肾病的治疗作用及机制[J].天津医药,2011,39(6)：557-559.
[102]赵君,谭小月,张勉等.五味子合剂对糖尿病肾病小鼠肾组织MCP-1及iNOS表达的影响[J].天津医药,2012,40(6)：594-597.
[103]冯士华,王庆周,李粉格等.五味子不同溶剂提取物对糖尿病小鼠血糖的影响[J].辽宁中医药大学学报,2011,13(1)：192-194.
[104]Bae H, Kim R, Kim Y, et al. Effects of Schisandra chinensis Baillon (Schizandraceae) on lipopolysaccharide induced lung inflammation in mice [J]. J Ethnopharmacol,2012,142(1):41-47.
[105]陈己明,陈东成.五味子汤合化瘀药对弥漫性肺纤维化的疗效观察[J].四川中医,2003,21(11)：41-42.
[106]翟华强,张硕峰,高明超等.麻黄和五味子对肺纤维化大鼠肺组织病理形态的影响[J].中西医结合学报,2011,9(5)：553-557.
[107]李曙芳,刘田福,郭民等.五味子乙素对二氧化硅致大鼠肺损伤的保护作用[J].中国比较医学杂志,2009,19(5)：30-36.
[108]樊林花,刘田福,郭民等.五味子乙素对染矽尘大鼠肺组织一氧化氮水平和诱导型一氧化氮合酶mRNA表达动态变化的影响[J].中国药理学通报,2011,27(2)：225-258.
[109]郭民,樊林花,刘田福等.五味子乙素对实验性矽肺大鼠肺组织MMP-2和TMP-1蛋白含量的影响[J].中国新药杂志,2012,21(9)：1059-1066.
[110]樊林花,刘田福,郭民等.五味子乙素抑制染二氧化硅大鼠肺组织环氧合酶-2mRNA和前列腺素E2表达[J].中国药理学与毒理学杂志,2012,26(1)：68-72.
[111]姜燕,贾有志.日本五味子木脂素成分研究概况[J].国外医药植物药分册,1991,6(3)：106-111.
[112]Y Ikeyaa, H Taguchia, H Mitsuhashi, et al. A lignan from Schizandra chinensis [J]. Phytochemistry,1988,27(2):69-573.
[113]李钊,杨永进,李军等.复方五味子含漱液治疗复发性口腔溃疡的近期疗效观察[J].中国实验方剂学杂志,2010,16(9)：202-203.
[114]李明,孙玲.自制五味子生肌象皮膏治疗慢性下肢溃疡86例[J].中医外治杂志,2009,18(1)：62.
[115]徐爱仁,马卫成,应景艳等.五味子提取物对大鼠肾缺血再灌注损伤保护研究[J].现代实用医学,2010,22(3)：328-329.
[116]姚凝.甘肃产华中五味子对实验性肾阴虚型小鼠血清超氧化物歧化酶、活性氧的影响[J].中国中医药信息杂志,2005,12(5)：33-34.
[117]彭国瑞,许志奇,曾祥国等.五味子对家兔泌尿生殖系统酶组织化学的影响及其抗衰延老作用的初步观察[J].上海中医药杂志,1989,(2)：43-45.
[118]刘巍,徐兆发,杨海波等.五味子乙素对汞性大鼠急性肾损伤的影响[J].中国工业医学杂志,2011,24(2)：89-92.
[119]陈延镛,舒增宝,黎莲娘等.北五味子的研究-北五味子降谷丙转氨酶有效成分的分离和鉴定[J].中国科学,1976,1：98-99.
[120].Y Ikeya, T Teihachiro, H Sasaki, et al. The constituents of Schizandra chinensis Baill.Ⅵ.13C nuclear magnetic resonance spectroscopy of dibenzocyclooctadiene lignans[J]. ChemPharmBull,1980,28(8):2414-2421.
[121].官艳丽,曹沛,郁开北等.北五味子化学成分的研究[J].中草药,2006,37(2)：18-20.
[122].苑广信.五味子质量控制方法及其提取物体外抗氧化活性研究[D].吉林大学博士论文,2012：16-20.
[123].王慧竹.五味子藤皮活性成分提取、分离及鉴定[D].吉林大学硕士论文,2008：19-25.
[124].陈延铺,黎莲娘.北五味子的研究-五味子酯甲和五味子酯乙的化学结构测定[J].化学学报,1976,34：45-46.
[125]. M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal Biochem.7(1976)248-254.
[126]. Gandhic C C, Kellyl R M, Wiley R qet al.Impaired acquisition of a Morris water maze task following selective destruction of cerebellar purkinje cells with OX7-saporin[J].Behav. Brain. Res.,2000,109(l):37-47.
[127]. Pouzet B, Zhang W N,Feldon J,et al.Hippocampal lesioned rats are able to learn a spatial position using non-spatial strategies [J].Behav.Brain.Res.2002,133(2):279-291.
[128].董晓华,张丹参,房杰.大黄酚对东莨菪碱致小鼠学习记忆障碍的作用及脑内NO和NOS的影响[J].河北北方学院学报,2009,26(1)：7-9.
[129]Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease [J].Free Radic Biol Med,1997,23(1):134-147
[130]. Moreira PI, Santos MS, Oliveira CR, et al.Alzheimer disease and the role of free radicals in the pathogenesis of the disease [J]. CNS Neurol Disord Drug Targets.2008,7(1):3-10
[131]. Dubinina EE, Pustygina AV Free radical processes in aging, neurodegenerative diseases and other pathological states [J]. Biomed Khim.2007,53(4):351-72
[132]. Zhu X, Su B, Wang X, et al. Causes of oxidative stress in Alzheimer disease [J].Cell Mol Life Sci.2007,64(17):2202-10
[133].Carney JM, Carney'AM. Role of protein oxidation in aging and in age-associated neurodegenerative disease [J].Life Sci,1994,55:2097-2103
[134]. Markesbery WR, Lovell MA. Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment [J].Arch Neurol.2007,64(7):954-6
[135]. Shi Q, Gibson GE. Oxidative stress and transcriptional regulation in Alzheimer disease [J].Alzheimer Dis Assoc Disord.2007,21(4):276-91
[136].吴正治,张艳萍,王怀龄等.补肝养髓方对自发老年性痴呆模型氧自由基损伤的定性定量研究[J].中国中医药科技,2007,4(6)：442-444
[136]Halliwell B. Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment [J]. Drugs Aging,2001,18(9):685-716
[138].Richardson JS. Free radicals in the genesis of Alzheimer's disease [J].Ann. N.Y Acad. Sci.1993,695:73
[139].Manczak M, Anekonda TS, Henson E, et al. Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons:implications for free radical generation and oxidative damage in disease progression [J].Hum Mol Genet,2006,15(9):1437-49
[140]. Ouyang S, Sun LS, Guo SL, et al. Effects of timosaponins on learning and memory abilities of rats with dementia induced by lateral cerebral ventricular injection of amyloid beta-peptide [J]. Di Yi Jun Yi Da Xue Xue Bao,2005,25(2):121-6
[141].李瑞芹,胡文祥.增强学习记忆药物的研究进展[J].中国现代医药杂志,2007,9(7)：122-124
[142]赵焕英,段春礼,范春香等.高效液相色谱同时检测生物样本中8种单胺类神经递质[J].分析化学研究报告,2009,3(3)：330-334.
[143]黄晓东.五味子和桔梗多糖对人结直肠癌CD133+/CD44+细胞生物学行为的影响[D].吉林大学博士论文,2012：58-68.
[2]高建平.五味子南五味子基源植物的比较研究[D].上海：复旦大学药学院,2003.
[2]陈道峰,王彦涵,高建平等.植物化学分类学(周荣汉)[M].上海：上海科技出版社,2005：451-452.
[3]陈延镛,舒增宝,黎莲娘等.北五味子的研究-北五味子降谷丙转氨酶有效成分的分离和鉴定[J].中国科学,1976,(1)：98-99.
[4]陈延铺,黎莲娘.北五味子的研究-五味子酯甲和五味子酯乙的化学结构测定[J].化学学报,1976,(34)：45-46.
[5]宋万志,童玉懿.五味子属植物木脂素类资源的研究[J].天然产物研究与开发,1990,2(4)：51-58.
[6]汤臣康.五味子的化学和药理研究的新进展[J].西北药学杂志,1994,9(16)：278-282.
[7]宋万志.五味子科植物的木脂素类成分及生物活性与国内资源[J].天然产物研究与开发,1991,3(1)：68-80.
[8]谢蓝.五味子类木脂素的化学研究进展[J].中国药物化学杂志,1992,2(2)：65-80.
[9]JS Liu, SD Fang, MF Huang, et al. Structure on the Active Principles of Schisandra sphenanthera Rehd.et Walls [J]. Sci Sin,1978,21(4):483-502.
[10]Y Ikeya, T Teihachiro, Y Itiro. The Constituents of Schisandra chinensis Ball.ⅩⅡ.Is-olation and Structure of a New Lignan Gomisin R the Absolute Structure of Wuweizisu C and Isolation of Schisantherin D [J]. Chem Pharm Bull,1982,30(9):3207-3211.
[11]Y Ikeya, T Teihachiro, Y Itiro. The Constituents of Schisandra chinensis Ball.I.Isolat-ion and Structure Determination of Five New Lignans Gomisin A B C F and G and the Absolute Structure of Schizandrin [J]. Chem Pharm Bull1979,27(6):1383-1394.
[12]Y Ikeya, T Teihachiro, Y Itiro. The Constituents of Schisandra chinensis Ball.The Cleavage of the Methylenedioxy Moiety Lead Tetraacetate in Benzene and the Structrure of Angeloylgomisin Q [J]. Chem Pharm Bull,1979,27(10):2536-2538.
[13]刘嘉森,黄梅芬.华中五味子的研究Ⅳ安五酸和d1-安五脂素的结构及d-表加巴辛的绝对构型[J].化学学报,1984,42(3)：264-270.
[14]Yang XW, Miyashiro H, Hattori M,Namba T, et al. Isolation of novel lignans, heteroclitins F and G, from the stems of Kadsura heteroclita, and anti-lipid peroxidative actions of heteroclitins A-G and related compounds in the in vitro rat liver homogenate system [J]. Chem Pharm Bull,1992,40(6):1510-1516.
[15]Matsushima Y, Amemiya R, Liu JS, et al. Directcurrent therapy with chemotherapy for the local control of lung cancer [J]. Nippon Gan Chiryo Gakkai Shi,1989,24(10):2341-2348.
[16]Takani M, Ohya K, Takahashi K, et al. Studies on constituents of medicinal plants XXII Constituents of Schizandra nigra Max [J]. Chem Pharm Bull,1979,27(6):1422-1425.
[17]Wang HJ, Chen YY, Liang XT, et al. The structure of a new lignin diol [J]. Chinese Chemical Letters,1993,4(1):31-32.
[18]Ademar A, Silva F, Sergio A, et al. Tetrahydrofuran Lignans from Nectandra megapotamica with Trypanocidal Activity [J]. J Nat Prod,2004,67(1):42-45.
[19]Chen H, Zhang M, Qu Z, et al. Antioxidant activities of different fractions of polysaccharide conjugates from green tea (Camellia sinensis)[J]. Food Chemistry,2008,10(6):559-563.
[20]Jiang YH, Jiang XL, Wang P, et al. The antitumor and antioxidative activities of polysaccharides isolated from Isaria farinosa B05[J]. Microbiological Research,2008,16(3):424-430.
[21]Yuan JF, Zhang ZQ,Fan ZC, et al. Antioxidant effects and cytotoxicity of three purified polysaccharides from Ligusticum chuanxiong Hort [J]. Carbohydrate Polymers,2008,(74):822-827.
[22]Chi AP, Chen JP, Wang ZZ, et al. Morphological and structural characterization of a polysaccharidefrom Gynostemma pentaphyllum Makino and its anti-exercise fatigue activity [J]. Carbohydrate Polymers,2008,(74):868-874.
[23]Arumugam S, Hanumantha RBR, Periasamy S, et al. Anti-peroxidative and anti-hyperlipidemic nature of Ulva lactuca crude polysaccharide on D-Galactosamine induced hepatitis in rats [J]. Food and Chemical Toxicology,2008,(46):3262-3267.
[24]徐世枕,王彩霞,李广全等.北五味子粗多糖的提取与成分分析[J].中国药物化学杂志,1992,2(1)：44-48.
[25]姜波,孙静,刘春等.五味子水溶性多糖提取及纯化工艺的优化[J].时珍国医国药,2009,20(10)：2614-2616.
[26]孟宪军,那广宁,高晓旭等.北五味子多糖的分离纯化研究[J].食品科技,2008,33(11)：197-199.
[27]张胜娜,吴素香.南北五味子挥发油化学成分及药理作用研究进展[J].中药材,2007,30(1)：118-120.
[28]戴好富,谭宁华,周俊等.北五味子挥发性化学成分研究[J].中草药,2005,6(9)：1309-1310.
[29]谷昊,张兰杰,辛广.北五味子叶挥发油化学成分分析[J].鞍山师范学院学报,2009,11(2)：38-41.
[30]孙广仁,杨文胜滕,玉辉等.五味子茎皮挥发油的化学成分研究[J].吉林林学院学报,1991,7(3)：18-21.
[31]李斌,李元甦,孟宪军等.超临界C02萃取北五味子藤茎挥发油的GC-MS分析[J].食品工业科技,2001,32(2)：106-108.
[32]李晓宁,崔卉,宋又群.辽五味子果实挥发油成分的鉴定[J].药学学报,2001,36(3)：215-219.
[33]王炎,王进福,尤宏.北五味子种子挥发油的GC/MS分析[J].中国药学杂志,2001,36(2)：91-92.
[34]刘亚敏,刘玉民,李鹏霞.超临界CO2流体萃取-GC-MS分析南北五味子挥发油成分[J].食品科学,2011,32(6)：204-208.
[35]林伟卓,陈玉海.北五味子全氮及氨基酸含量测定[J].特产研究,1998,(1)：35-36.
[36]王丽薇,周长新, Bernd Schneider等.‘北五味子化学成分研究[J].中国现代应用药学杂志,2006,23(5)：363-365.
[37]官艳丽,曹沛,郁开北.北五味子化学成分的研究[J].中草药,2006,37(2)：185-187.
[38]汪有初,周俊,谭宁华.五味子的环二肽及其合成[J].药学学报,1999,34(1)：19-22.
[39]Hu D, Li C, Han N, Miao L, et al. Deoxyschizandrin isolated from the fruits of Schisandra chinensis ameliorates Aβ1-42-induced memory impairment in mice [J].Planta Med.2012,78(12):1332-1336.
[40]Giridharan W, Thandavarayan RA, Sato S, et al. Prevention of scopolamine-induced memory deficits by schisandrin B, an antioxidant lignan from Schisandra chinensis in mice [J]. Free Radic Res.2011,45(8):950-9588.
[41]王艳春,任旷,范红艳.五味子总素对记忆障碍模型小鼠学习记忆的改善作用[J].中国中药杂志,2011,36(23)：3310-3313.
[42]王艳春,任旷,范红艳.五味子醇甲对记忆障碍模型小鼠学习记忆的影响[J].中国药学杂志,2011,46(14)：1097-1103.
[43]于方,拓西平,吕建勇等.华中五味子酮对阿尔茨海默病样大鼠学习记忆功能及海马区核因子κB、诱导型一氧化氮合酶表达的影响[J].第二军医大学学报,2007,28(12)：1351-1355.
[44]李楚华,肖鹏,欧阳效等.益智Ⅱ号促进小鼠记忆保持的观察与分析[J].华南师范大学学报(自然科学版),2004,(1)：112-116.
[45]Yang JM, Lp PS, Che CT, et al. Relaxant effects of Schisandra chinensis and its major lignans on agonists-induced contraction in guinea pig ileum. Phytomedicine [J],2011,18(13):1153-1160.
[246]霍艳双,陈晓辉,李康.北五味子的镇静、催眠作用[J].沈阳药科大学学报,2005,25(2)：126-128.
[47]张林魁,钮心懿.五味子醇甲对中枢神经系统单胺类递质的影响[J].中国 医学科学研学报,1991,13(1)：13-16.
JS, L HK, D NT. Liganswith inhibitory activity NFAT transcription from Schisandra Chinenisis [J]. Plant a Medica,2003,69(1):63-64.
[249]齐治,崔景荣,田建柱等.五味子果实挥发油对中枢神经系统的药理作用研究[J].北京医科大学学报,1988,20(6)：457-412.
[50]Chen Y, Tang J, Wang X, et al. An immunostimulatory polysaccharide (SCP-IIa) from the fruit of Schisandra chinensis (Turcz.) Baill. Int J Biol Macromol [J].2012,50(3):844-848.
[251]孙文娟,吕文伟,于晓凤.北五味子粗多糖抗衰老作用的实验研究[J].中国老年学杂志,2001,11(21)：454-455.
[52]苗明三.五味子多糖对衰老模型小鼠的影响[J].中国医药学报,2002,17(3)：187-188.
[53]门红军,刘立.北五味子粗多糖对大鼠自由基代谢的影响[J].吉林中医药,2003,23(7)：48.
[54]刘晓瑞.北五味子抗衰老作用的实验研究[J].中国老年学杂志,2005,25(12)：1562.
[55]辛晓林,张桂春,黄清荣.五味子镇痛效果研究[J].安徽农业科学,2009,37(32)：15842-15843.
[56]刘丹娜,罗晶.不同剂量五味子多糖灌胃给药镇痛作用的观察[J].第四军医大学学报,2008,29(12)：1115-1117.
[57]李庆耀,孙全忠,陈道峰等.两种南五味子属药用植物油性成分的镇痛作用[J].上海医科大学学报,1999,26(1)：56.
[58]孙侃.北五味子对蛙心强心作用的初步观察[J].新医学,1972,(6)：33-35.
[59]刘菊秀,陈静,苗戎等.北五味子对心脏电活动及收缩力的影响[J].中草药,1999,30(4)：280-281.
[60]刘菊秀,苗戎,陈静等.五味子对心肌力学和心率的影响[J].中草药,1999,30(2)：122-124.
[61]曾祥国,许志奇,彭国瑞等.五味子对家兔心血管酶组化的药理作用研究 [J].四川中医,1990,(4)：10-12.
[62]映红,李湘楚,罗德生.五味子提取液对动物缺氧及心肌缺血的保护作用[J].咸宁医学院学报,1998,12(2)：79-82.
[63]Park JY, Choi YW, Yun JW. Gomisin J from Schisandra chinensis induces vascular relaxation via activation of endothelial nitric oxide synthase [J]. Vascul Pharmacol.2012,57(2-4):124-130.
[64]Park JY, Shin HK, Lee YJ, et al. The mechanism of vasorelaxation induced by Schisandra chinensis extract in rat thoracic aorta [J]. J Ethnopharmacol,2009,121(1):69-73.
[265]李庆耀,陈道峰,江明华.戈米辛J和异型南五味子丁素对大鼠胸主动脉的作用[J].上海医科大学学报,1999,26(4)：280-282.
[66]蒋仕丽,章蕴毅,陈道峰.异型南五味子丁素、五味子酚和(+)-安五脂素对血小板聚集的影响[J].复旦学报,2005,32(4)：467-470.
[67]林童俊.五味子酚和丹酚酸A抗氧化作用机理及对阿霉素心脏毒性的保护作用[J].生理科学进展,1991,22(4)：342-345.
[68]刘扬,徐广智,林童俊等.五味子酚对AQ损伤心肌药理作用的ESR研究[J].科学通报,1993,38(19)：1809-1812.
[69]Zhu M, Yeung RY, Lin KF, et al. Improvement of phase I drug metabolism with Schisandra chinensis against CCl4hepatotoxicity in a rat model [J]. Planta Med,2000,66(6):521-5.
[70](Zhu M, Lin KF, Yeung RY, et al. Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4intoxication model [J]. J Ethnopharmacol,1999,67(1):61-68.
[71]齐彦,郭丽新,周迎春.五味子对四氯化碳所致小鼠急性肝损伤的作用研究[J].中医药学报,2009,37(4)：26-27.
[72]许珂玉,柳春.五味子多糖对CCl4诱导的肝损伤大鼠亚细胞水平的保护作用[J].中国老年学杂志,2011,31(8)：1352-1353.
[73]蔡绍先,陈玮莹,吴健谊等.五味子提取物对CC14中毒大鼠肝超微结构的保护作用[J].癌变、畸变、突变,2010,22(1)：52-54.
[74]陈玮莹,温博贵,郑瑞明等.五味子对CC14中毒大鼠肝细胞核基质蛋白和结构的保护作用[J].免疫学杂志,22(4)：455-459.
[75]蔡晶,黄巧冰,迟德彪.五味子乙素对H2O2损伤人肝细胞Fas通路的影响[J].南方医科大学学报,2012,32(4)：583-585.
[76]张锦楠,李亚伟,徐艳霞.甘草和五味子对大鼠肝微粒体CYP450诱导作用的研究[J].中国药学杂志,2002,37(6)：424-426.
[77]刘耕陶,包天桐,巍怀玲等.五味子乙素对对小鼠肝细胞微粒体细胞细胞色素P-450的诱导作用[J].药学学报,1980,15(4)：206-211.
[78]Iwata H, Tezuka Y, Usia T. Inhibition of human liver microsomal CYP3A4and CYP2D6by extracts from78herbal medicines [J]. J Tradit Med,2004,21:281
[79]Iwata H. Identification and characterization of potent CYP3A4inhibitors in schisandra fruit extract [J]. Drug Metab Dispos,2004,32:1351-1358.
[80]陈倩,吴育晶,程能能.五味子提取物对大鼠肝CYP3A酶的双重作用[J].药学学报,2010,45(9)：1194-1198.
[81]孙成仁,彭正松.北五味子的抑菌作用[J].四川师范学院学报,1993,14(3)：200-202.
[82]刘志春,王小丽.五味子等29种中草药的体外抑菌实验[J].赣南医学院学报,2004,24(5)：509-511.
[83]边才苗,杨云斌,费杰等.五味子提取物体外抑菌作用初探[J].浙江中医药大学学报,2009,33(1)：122-123.
[84]邹金美,陈芸,陈秀桥等.五味子提取物的抑菌活性研究[J].江苏农业科学,2011,39(5)：400-402.
[85]张锐利,包东东,刘华英.不同提取方法对北五味子提取物抑菌活性的影响[J].安徽农业科学,2010,38(24)：13177-13179.
[86]吴少辉,叶伟娟,赵婷等.南五味子乙醇提取物对食品腐败细菌的抑制活性研究[J].中国食品学报,2012,12(8)：104-109.
[87]李斌,孟宪军,薛雪等.北五味子乙素清除自由基及体外抑菌作用的研究[J].食品科学,2011,32(5)：79-82.
[88]许瑞波,高颖颖,万蓓蓓等.北五味子叶多糖的提取及抑菌活性[J].食品科学,2012,33(20)：33-37.
[89]Gnabre J, Unlu I, Chang TC, et al. Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: Structure-activity relationships [J]. J Chromatogr B Analyt Technol Biomed Life Sci.2010,878(28):2693-2700.
[90]Hwang D, Shin SY, Lee Y, et al. A compound isolated from Schisandra chinensis induces apoptosis [J]. Bioorg Med Chem let,2011,21(20):6054-6057.
[91]禹洁,刘培勋,龙伟.五味子总木脂素的分离纯化与体外抗肿瘤活性研究[J].中国药师,2009,12(12)：1718-1720.
[92]李玲,胡迅,潘铿荣等.五味子乙素对MRP介导的肿瘤多药耐药逆转作用的研究[J].同济大学学报,2006,27(6)：19-23.
[93]孙华,刘耕陶.五味子果仁醇提取物含药血清逆转肿瘤多药耐药及抑制耐药糖蛋白(P-gp)的作用[J].中国新药杂志,2009,18(12)：1130-1135.
[94]黄玲,陈玲,张振林.五味子多糖对荷瘤小鼠血液SOD和MDA的影响[J].福建中医学院学报,2005,15(1)：28-29.
[95]黄玲,陈玲,张振林.五味子多糖对荷瘤鼠瘤体抑制作用的病理学观察[J].中药材,2004,27(3)：202-203.
[96]Zhang M, Liu M, Xiong M, et al. Schisandra chinensis fruit extract attenuates albuminuria and protects podocyte integrity in a mouse model of streptozotocin-induced diabetic nephropathy [J]. J Ethnopharmacol,2012,141(1):111-118.
[95]安丽萍,王英平,刘晓梅等.五味子油对链脲佐菌素诱导的2型糖尿病大鼠的影响[J].中草药,2012,43(3)：552-556.
[96]柴可夫,覃志成,王亚丽.北五味子油对糖尿病小鼠胰岛细胞形态及功能的影响[J].中国中医药科技,2007,14(3)：177-178.
[99]安丽萍,王英平,王春梅等.五味子油对2型糖尿病大鼠胰岛B细胞凋亡的影响[J].2012,38(1)：84-88.
[100]刘馨,刘学政.五味子油对2型糖尿病胰岛素抵抗大鼠的作用及机制[J].中国生化药物杂志,2012,33(6)：800-802.
[101]刘苗,张勉之,谭小月.复方五味子醇提液对糖尿病肾病的治疗作用及机制[J].天津医药,2011,39(6)：557-559.
[102]赵君,谭小月,张勉等.五味子合剂对糖尿病肾病小鼠肾组织MCP-1及iNOS表达的影响[J].天津医药,2012,40(6)：594-597.
[103]冯士华,王庆周,李粉格等.五味子不同溶剂提取物对糖尿病小鼠血糖的影响[J].辽宁中医药大学学报,2011,13(1)：192-194.
[104]Bae H, Kim R, Kim Y, et al. Effects of Schisandra chinensis Baillon (Schizandraceae) on lipopolysaccharide induced lung inflammation in mice [J]. J Ethnopharmacol,2012,142(1):41-47.
[105]陈己明,陈东成.五味子汤合化瘀药对弥漫性肺纤维化的疗效观察[J].四川中医,2003,21(11)：41-42.
[106]翟华强,张硕峰,高明超等.麻黄和五味子对肺纤维化大鼠肺组织病理形态的影响[J].中西医结合学报,2011,9(5)：553-557.
[107]李曙芳,刘田福,郭民等.五味子乙素对二氧化硅致大鼠肺损伤的保护作用[J].中国比较医学杂志,2009,19(5)：30-36.
[108]樊林花,刘田福,郭民等.五味子乙素对染矽尘大鼠肺组织一氧化氮水平和诱导型一氧化氮合酶mRNA表达动态变化的影响[J].中国药理学通报,2011,27(2)：225-258.
[109]郭民,樊林花,刘田福等.五味子乙素对实验性矽肺大鼠肺组织MMP-2和TMP-1蛋白含量的影响[J].中国新药杂志,2012,21(9)：1059-1066.
[110]樊林花,刘田福,郭民等.五味子乙素抑制染二氧化硅大鼠肺组织环氧合酶-2mRNA和前列腺素E2表达[J].中国药理学与毒理学杂志,2012,26(1)：68-72.
[111]姜燕,贾有志.日本五味子木脂素成分研究概况[J].国外医药植物药分册,1991,6(3)：106-111.
[112]Y Ikeyaa, H Taguchia, H Mitsuhashi, et al. A lignan from Schizandra chinensis [J]. Phytochemistry,1988,27(2):69-573.
[113]李钊,杨永进,李军等.复方五味子含漱液治疗复发性口腔溃疡的近期疗效观察[J].中国实验方剂学杂志,2010,16(9)：202-203.
[114]李明,孙玲.自制五味子生肌象皮膏治疗慢性下肢溃疡86例[J].中医外治杂志,2009,18(1)：62.
[115]徐爱仁,马卫成,应景艳等.五味子提取物对大鼠肾缺血再灌注损伤保护研究[J].现代实用医学,2010,22(3)：328-329.
[116]姚凝.甘肃产华中五味子对实验性肾阴虚型小鼠血清超氧化物歧化酶、活性氧的影响[J].中国中医药信息杂志,2005,12(5)：33-34.
[117]彭国瑞,许志奇,曾祥国等.五味子对家兔泌尿生殖系统酶组织化学的影响及其抗衰延老作用的初步观察[J].上海中医药杂志,1989,(2)：43-45.
[118]刘巍,徐兆发,杨海波等.五味子乙素对汞性大鼠急性肾损伤的影响[J].中国工业医学杂志,2011,24(2)：89-92.
[119]陈延镛,舒增宝,黎莲娘等.北五味子的研究-北五味子降谷丙转氨酶有效成分的分离和鉴定[J].中国科学,1976,1：98-99.
[120].Y Ikeya, T Teihachiro, H Sasaki, et al. The constituents of Schizandra chinensis Baill.Ⅵ.13C nuclear magnetic resonance spectroscopy of dibenzocyclooctadiene lignans[J]. ChemPharmBull,1980,28(8):2414-2421.
[121].官艳丽,曹沛,郁开北等.北五味子化学成分的研究[J].中草药,2006,37(2)：18-20.
[122].苑广信.五味子质量控制方法及其提取物体外抗氧化活性研究[D].吉林大学博士论文,2012：16-20.
[123].王慧竹.五味子藤皮活性成分提取、分离及鉴定[D].吉林大学硕士论文,2008：19-25.
[124].陈延铺,黎莲娘.北五味子的研究-五味子酯甲和五味子酯乙的化学结构测定[J].化学学报,1976,34：45-46.
[125]. M.M. Bradford, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal Biochem.7(1976)248-254.
[126]. Gandhic C C, Kellyl R M, Wiley R qet al.Impaired acquisition of a Morris water maze task following selective destruction of cerebellar purkinje cells with OX7-saporin[J].Behav. Brain. Res.,2000,109(l):37-47.
[127]. Pouzet B, Zhang W N,Feldon J,et al.Hippocampal lesioned rats are able to learn a spatial position using non-spatial strategies [J].Behav.Brain.Res.2002,133(2):279-291.
[128].董晓华,张丹参,房杰.大黄酚对东莨菪碱致小鼠学习记忆障碍的作用及脑内NO和NOS的影响[J].河北北方学院学报,2009,26(1)：7-9.
[129]Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease [J].Free Radic Biol Med,1997,23(1):134-147
[130]. Moreira PI, Santos MS, Oliveira CR, et al.Alzheimer disease and the role of free radicals in the pathogenesis of the disease [J]. CNS Neurol Disord Drug Targets.2008,7(1):3-10
[131]. Dubinina EE, Pustygina AV Free radical processes in aging, neurodegenerative diseases and other pathological states [J]. Biomed Khim.2007,53(4):351-72
[132]. Zhu X, Su B, Wang X, et al. Causes of oxidative stress in Alzheimer disease [J].Cell Mol Life Sci.2007,64(17):2202-10
[133].Carney JM, Carney'AM. Role of protein oxidation in aging and in age-associated neurodegenerative disease [J].Life Sci,1994,55:2097-2103
[134]. Markesbery WR, Lovell MA. Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment [J].Arch Neurol.2007,64(7):954-6
[135]. Shi Q, Gibson GE. Oxidative stress and transcriptional regulation in Alzheimer disease [J].Alzheimer Dis Assoc Disord.2007,21(4):276-91
[136].吴正治,张艳萍,王怀龄等.补肝养髓方对自发老年性痴呆模型氧自由基损伤的定性定量研究[J].中国中医药科技,2007,4(6)：442-444
[136]Halliwell B. Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment [J]. Drugs Aging,2001,18(9):685-716
[138].Richardson JS. Free radicals in the genesis of Alzheimer's disease [J].Ann. N.Y Acad. Sci.1993,695:73
[139].Manczak M, Anekonda TS, Henson E, et al. Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons:implications for free radical generation and oxidative damage in disease progression [J].Hum Mol Genet,2006,15(9):1437-49
[140]. Ouyang S, Sun LS, Guo SL, et al. Effects of timosaponins on learning and memory abilities of rats with dementia induced by lateral cerebral ventricular injection of amyloid beta-peptide [J]. Di Yi Jun Yi Da Xue Xue Bao,2005,25(2):121-6
[141].李瑞芹,胡文祥.增强学习记忆药物的研究进展[J].中国现代医药杂志,2007,9(7)：122-124
[142]赵焕英,段春礼,范春香等.高效液相色谱同时检测生物样本中8种单胺类神经递质[J].分析化学研究报告,2009,3(3)：330-334.
[143]黄晓东.五味子和桔梗多糖对人结直肠癌CD133+/CD44+细胞生物学行为的影响[D].吉林大学博士论文,2012：58-68.