针灸对细胞自噬水平的调控及其在神经退行性疾病中的作用

针灸作为传统中医的一种重要治疗方式,能够有效改善帕金森病、老年痴呆、亨廷顿氏病等神经退行性疾病的相关症状。然而,针灸作用的分子机制长期以来没有得到明确的阐释。近年来,研究发现针灸可以通过提高细胞自噬水平而促进异常积聚蛋白的清除,从而达到治疗和改善神经退行性疾病的目的。自噬是细胞清除受损细胞器及细胞内错误折叠或异常聚集蛋白质的过程,对细胞稳态的维持和细胞内物质能量的循环具有重要的作用。帕金森病、老年痴呆、亨廷顿氏病等神经退行性疾病的发生发展往往与基础水平自噬下降有关。文章综述了针灸对自噬效应的调控及其对神经退行性疾病的作用的研究进展,并对针灸在神经退行性疾病中的应用作了展望。     

中药治疗阿尔茨海默病的实验研究进展

阿尔茨海默病(Alzheimer's disease,AD)是一种进行性的退行性神经病变,目前尚无治愈方法。用中药治疗AD一直是研究热点,复方、单味药的实验研究逐渐深入。通过查阅文献,对近年来中药治疗AD的一些实验进行整理,主要从增强胆碱能系统功能、减轻Aβ聚集、抗炎、清除自由基、减少神经细胞凋亡等方面进行论述。     

尿石素干预神经退行性疾病的研究进展

鞣花单宁是一类中药有效成分。尿石素类化合物是鞣花单宁体内代谢产物及效应成分,具有抗炎、抗氧 化应激、抗凋亡等生物活性。尿石素可通过血脑屏障发挥神经保护活性作用,是干预神经退行性疾病的潜在活 性小分子。神经退行性疾病是一类由神经元结构或功能逐渐丧失而引发的不可逆性疾病。近年来其发病率不断 上升且严重威胁着患者的健康和生活质量,但有效药物始终匮乏。该文综述了尿石素对常见的神经退行性疾病 如阿尔茨海默病、帕金森病等的神经保护作用机制的研究进展,为其进一步的研究和应用提供参考。     

姜黄素对阿尔茨海默病及帕金森病的相同作用机制研究进展

姜黄素是提取自姜黄科、天南星科等植物中的一种疏水性二酮类化合物。研究表明姜黄素及其衍生物的抗炎和抗氧化作用在神经退行性疾病中发挥重要作用。近年来,姜黄素对阿尔茨海默病及帕金森病的作用机制研究也越来越多。综合姜黄素对阿尔茨海默病及帕金森病的相同作用机制研究成果,为更好探索姜黄素在神经退行性疾病的作用机制提供基础研究思路及开发研究安全可靠的药物提供参考。     

老鹳草属药用植物鞣质成分及防治阿尔茨海默病研究进展

阿尔茨海默病（AD）是一种神经系统退行性疾病，其发病机制主要有β淀粉样蛋白（Aβ）过度沉积、神经炎症反应、微管相关蛋白（Tau蛋白）过度磷酸化等，目前临床还没有找到有效的治疗药物。而传统中草药可以通过多成分多靶点发挥抗AD作用成为研究热点。老鹳草作为我国的一味传统中药已有600余年的临床药用历史，其具备巨大的药用潜力和广阔的应用前景。老鹳草属药用植物的化学成分类型主要包括鞣质、黄酮、有机酸及挥发油等。研究表明，中药老鹳草中多种鞣质化学成分具有改善学习记忆能力和认知功能障碍等药理活性，其机制涉及抗Aβ、调节Tau蛋白、抗氧化、抗炎、抑制乙酰胆碱酯酶活性等，其能通过多途径、多靶点抑制神经元的退行性改变，从而有效防治阿尔茨海默病等神经退行性疾病。通过查阅分析相关文献后，着重对中药老鹳草属中多种鞣质组分及其在防治阿尔茨海默病方面的研究进行综述。并通过探讨中药老鹳草属植物中的鞣质组分及其作用机制，筛选出潜在治疗阿尔茨海默病等神经退行性疾病的药物组分，为其进一步开发和临床应用提供理论基础及研究思路。     

基于维生素D轴的淫羊藿苷干预阿尔兹海默病机制探讨

阿尔茨海默病是发生在老年及其前期的一种与老化有关的中枢神经系统退行性疾病,严重影响老年人的生活质量,是未来几十年要面临的严峻公共卫生问题之一。维生素D是重要的类固醇衍生物之一,在AD患者中存在普遍缺乏现象,且与认知能力改变具有密切相关性。小胶质细胞(MG)是中枢神经系统中重要的神经免疫细胞,其持续激活介导神经炎症,是引起神经退行性疾病的重要因素。课题组前期研究发现,淫羊藿苷干预阿尔茨海默病模型大鼠维生素D及VDR表达,抑制小胶质细胞的过度激活,改善阿尔茨海默病模型大鼠病情。由此课题组提出:淫羊藿苷可能通过维生素D轴调节小胶质细胞极化,参与控制炎症因子的释放,促进内源性神经营养因子的释放,发挥对阿尔茨海默病的治疗作用。     

PC12细胞作为氧化应激细胞模型的研究进展

在正常机体内,活细胞可以从不同来源持续产生自由基,如线粒体从电子传递链释放自由基,信号转导剂氧化亚氮等形成活性的亚硝基自由基,氧化还原反应中活化的金属通过Fenton反应和Haber-Weiss反应产生自由基,当种种原因导致体内过氧化氢( H2 O2)、一氧化氮(NO)、过氧自由基O2-等各种活性氧化物(reactive oxygen species,ROS)超过了机体内源性的抗氧化能力,则引起机体内氧化/抗氧化系统平衡失调,发生氧化应激损伤[1].多方面的神经病理学研究显示,神经退行性疾病的发生与供体的氧化产物水平增加有密切关系[2-5],因为脑和神经内含有大量的脂质、耗氧量较高,而神经元不能分裂,所以ROS蓄积引起的损伤有可能是疾病发生发展的重要诱因.     

补肾中药激活内源性神经干细胞与阿尔茨海默病的治疗

阿尔茨海默病本身能够一定程度诱导内源性NSCs的活化,以实现机体功能的代偿恢复,同时也说明随着病程的延长及年龄的逐渐增长,内源性NSCs的激活逐渐减少。补肾填髓中药能促进神经元细胞能量代谢和利用,激活内源性神经营养因子,促进神经元存活与再生。以生地黄、熟地黄、山茱萸等组成的补肾复方能改善阿尔茨海默病病人的认知功能。中药具有整体调节和多环节综合治疗的优势,以神经干细胞为切入点,着眼于补肾中药对神经干细胞在脑内增值、分化的规律与机制研究,探索出一条全新的内源性神经保护通路和神经功能重建的干预调节机制,为中医药在该领域深层次的研究开辟全新的思路和治疗靶点,从更深层次上阐明中药治疗阿尔茨海默病的内在机制。     

藏药红景天抗氧化作用在阿尔兹海默病中的研究进展

红景天作为传统藏药,其抗氧化性能够有效的抗自由基、抗脂质过氧化,降低体内自由基对细胞的氧化损害,抗衰老作用已经通过大量的细胞实验和动物实验得到证实;而阿尔兹海默病恰恰是与年龄相关的神经退行性中枢疾病,虽然目前发病机制尚不明确,但氧化应激对脑细胞的损伤被认为是重要的原因。研究发现红景天能发挥线粒体膜保护作用,提高机体自由基清除酶的表达,起到了清除细胞内活性氧聚集,减轻氧化应激的作用,从而减轻阿尔兹海默病患者的脑损伤。     

基于Keap1/Nrf2/ARE信号通路的天然产物在神经保护方面的研究进展

阿尔茨海默病、帕金森病、多发性硬化等神经退行性疾病的病理表现为异常蛋白质的聚集和积累、小胶质细胞激活和线粒体功能障碍等,最终导致神经元结构或功能逐渐丧失,并随着时间的推移而恶化,这些病理过程与活性氧（ROS）的产生有关,ROS会引起氧化应激并破坏蛋白质、脂质和DNA,引发细胞和组织损伤。Kelch样ECH相关蛋白1(Keap1)/核因子E2相关因子2(Nrf2)/抗氧化反应元件（ARE）信号通路是维持机体氧化还原平衡、防御氧化应激损伤的主要机制,Nrf2通过与细胞质中Keap1的解离和核转移,激活ARE相关的一系列抗氧化基因的表达,以保护机体免受氧化损伤,因此Keap1/Nrf2/ARE信号通路激活剂的发现与研究对神经退行性疾病的防治具有重要意义。天然产物因有显著的生物活性、不良反应小等特点,是新药研发的宝库。研究表明,多种天然产物能够激活Keap1/Nrf2/ARE信号通路,发挥神经保护作用。根据天然产物的结构特点,可分为黄酮类、萜类及挥发油类、多酚类和苯丙素类等。该文概述了Keap1/Nrf2/ARE信号通路调节疾病的内在机制,并总结了基于该信号通路的天然产物在神经保护方面的研究进...     

Neuroprotective mechanisms of ayurvedic antidementia botanical Bacopa monniera

Alzheimer's disease is a neurodegenerative disorder characterized by progressive dementia. Bacopa monniera is described in the Ayurvedic Materia Medica, as a therapeutically useful herb for the treatment of cognitive impairment, thus supporting its possible anti-Alzheimer's properties. Our studies have shown that Bacopa monniera reduces beta-amyloid deposits in the brain of an Alzheimer's disease animal model. The objective of this study was to establish the presence of endogenous substances in Bacopa monniera extract (BmE) that will impact components of the oxidative stress cascade such as the reduction of divalent metals, scavenging of reactive oxygen species, alterations of lipoxygenase activity and hydrogen peroxide-induced lipid peroxidation. The extract contained polyphenols and sulfhydryl contents suggestive of endogenous antioxidant activity. The results demonstrated that BmE reduced divalent metals, dose-dependently scavenged reactive oxygen species, decreased the formation of lipid peroxides and inhibited lipoxygenase activity. These data combined with our previous studies that have shown that BmE treatment reduces beta-amyloid levels in the brain of an Alzheimer's disease doubly transgenic mouse model of rapid amyloid deposition (PSAPP mice) suggesting mechanisms of action relevant to the treatment of Alzheimer's disease.     

三七皂苷对神经系统疾病药理作用机制研究进展

通过综述三七皂苷,包括三七总皂苷、三七三醇皂苷、三七二醇皂苷、人参皂苷Rg₁、人参皂苷Rb₁、人参皂苷Re和三七皂苷R₁对神经系统疾病(阿尔茨海默病、帕金森病、缺血性脑中风和抑郁症)的药理作用,对比分析三七皂苷对神经系统疾病的药理作用研究热点及潜在优势(如类雌激素作用),为进一步的药理研究提供参考,也为临床上对神经系统疾病的治疗、药物的研究开发提供新的思路。     

1,5-O-Dicaffeoyl-quinic Acid as a Novel Potential NMDA Receptor Inhibitor from Traditional Chinese Medicine Database by Virtual Screening

Objective Neurodegenerative diseases, such as ischemia, traumatic injury, Alzheimer’s disease, and Parkinson’s disease are characterized by neuronal loss and dysfunction. It is known that glutamate-induced toxicity plays an important role in neurodegenerative diseases. Glutamate toxicity seems to be mediated by excessive influx of Ca2+ into neuronal cells through activation of N-methyl-D-aspartate (NMDA) receptor. To search for potential NMDA receptor inhibitors in traditional Chinese medicine. Methods A series of computer methods including drug-likeness evaluation, ADMET tests as well as molecular docking have been used. Results 1,5-O-dicaffeoyl-quinic acid was identified as NMDA receptor inhibitor by virtual screening. Its neuroprotective activity was further confirmed by in vitro test. 1,5-O-dicaffeoyl-quinic acid showed strong neuroprotection against NMDA-induced cell injury. Conclusion 1,5-O-Dicaffeoyl- quinic acid may be regarded as a potential NMDA receptor inhibitor for the prevention and treatment of neurodegenerative disorders.     

中医药调节肠道菌群治疗神经退行性疾病研究进展

神经退行性疾病发病率日渐攀高，其有效治疗策略亟待研发。近年来多项研究逐步揭示肠道菌群影响中枢神经系统功能的作用机制，为靶向肠道菌群治疗神经退行性疾病的治疗手段提供了理论依据。中医药在疾病治疗中以多层面、多靶点、多通路见长，本文对肠道菌群与神经中枢的相互作用，神经退行性疾病中存在的肠道菌群紊乱，以及肠道菌群参与神经退行性疾病的发病机制进行了总结，并综述了中医药以调节肠道菌群为主要作用机制治疗神经退行性疾病的国内外研究，旨在展示中医药治疗神经退行性疾病的深入机制，为开发神经退行性疾病的新型治疗策略拓展新思路。     

��������ص��о���չ����Ӧ��ǰ��

??Chondroitin sulfate (CS) is a heterogeneous and negatively charged polysaccharide composed of repeating disaccharideunits, and has many pharmacological activities. CS has been recommended as symptomatic slow acting drugs for osteoarthritis (SYSADOA) in clinical practice. CS is shown to have promising prospect as a potential candidate for anti-metastasis of cancers and as a neurite outgrowth agent for neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease characterized by progressive loss of neurons.Moreover, CS is also involved in interaction with virus during its cell entry, wound healing and osteogenesis, and may be a promising drug candidate in these areas. Based on original publications, the research advances of CS in these areas and its applications were reviewed.The possibility of chemoenzymatic synthesis of specific CS chains as potential drugs was also discussed here, which may be used in the treatment of osteoarthritis, anti-metastasis of cancers, and so on.     

自噬在阿尔茨海默病中的作用及中药的干预作用

对近年来阿尔茨海默病(Alzheimer's disease,AD)与自噬相关性的研究及中药对自噬的调控作用进行介绍,对自噬的过程和相关分子机制、信号途径,自噬参与AD病理学表现的形成、神经元的缺失及与其他AD病理学表现,中药对自噬的影响,自噬在AD中的治疗意义进行总结.研究表明,自噬功能缺陷与多种神经退行性疾病密切相关,包括AD.集中介绍自噬在AD发生发展过程中的作用以及调控自噬在阻止或延缓AD发生,改善临床症状等方面的潜在治疗价值.在调节自噬,治疗AD等神经退行性疾病方面,关于中药的研究几乎处于空白状态.研究中药对神经细胞自噬的影响,通过调节自噬探讨中药治疗AD的潜在可能,并以此为基础,进行复方药物的选择,具有重要意义和极大的研究潜力.     

基于胶质淋巴系统探讨“毒损脑络”

络脉是经脉系统的分支,具有沟通表里上下、联系脏腑的作用,在支持气血运行方面呈现双向流动的特性,具有物质交换和新陈代谢的功能。脑为诸阳之会,脑络纵横交错,脑络渗灌气血以充实脑髓并敷布阳气以温煦脑神,为"脑主神明"提供物质基础和源动力。病理情况下脑络不通,毒邪内生,而致"毒损脑络"。"毒损脑络"病机学说不仅应用于中风病机研究中,而且拓展到痴呆等其他脑病中,推动了中医脑病病机理论的发展。新近发现脑内存在"胶质淋巴系统",是星形胶质细胞介导的脑脊液-脑间质液的交换流动系统。胶质淋巴系统把脑脊液中的葡萄糖、脂质、电解质和载脂蛋白E等营养物质和神经活性物质运送到脑组织,也能清除脑内代谢产物(如乳酸)、可溶性蛋白(如β-淀粉样蛋白和Tau蛋白)和异物,这是维持脑内环境稳态的重要液体流动系统。胶质淋巴系统的发现为神经系统疾病病理机制的研究提供了新视角,可能成为脑血管疾病、神经退行性疾病等神经精神系统疾病干预的新靶点。作为脑内广泛分布的代谢废物排出途径和物质运送系统的胶质淋巴系统可能是"脑络"病变的生物学基础,是中西医对"毒损脑络"认识的交叉点,从胶质淋巴系统探析"毒损脑络",有可能为揭示"毒损脑络"的现代内涵提供新的靶点。     

The diarylheptanoid (+)-aR,11S-myricanol and two flavones from bayberry (Myrica cerifera) destabilize the microtubule-associated protein tau

Target-based drug discovery for Alzheimer's disease (AD) centered on modulation of the amyloid β peptide has met with limited success. Therefore, recent efforts have focused on targeting the microtubule-associated protein tau. Tau pathologically accumulates in more than 15 neurodegenerative diseases and is most closely linked with postsymptomatic progression in AD. We endeavored to identify compounds that decrease tau stability rather than prevent its aggregation. An extract from Myrica cerifera (bayberry/southern wax myrtle) potently reduced both endogenous and overexpressed tau protein levels in cells and murine brain slices. The bayberry flavonoids myricetin and myricitrin were confirmed to contribute to this potency, but a diarylheptanoid, myricanol, was the most effective anti-tau component in the extract, with potency approaching the best targeted lead therapies. (+)-aR,11S-Myricanol, isolated from M. cerifera and reported here for the first time as the naturally occurring aglycone, was significantly more potent than commercially available (±)-myricanol. Myricanol may represent a novel scaffold for drug development efforts targeting tau turnover in AD.     

线粒体自噬与神经退行性疾病的关系及针灸调控机制探讨＊

线粒体自噬在线粒体数量和质量控制以及线粒体正常功能的维持中具有重要作用，与阿尔兹海默病、帕金森氏病等神经退行性疾病的发生发展密切相关。线粒体自噬过度和自噬障碍以及自噬相关基因发生突变等均影响退行性疾病病理进程。本文就线粒体自噬途径、线粒体自噬与神经退行性疾病的关系等作一综述，并探讨针灸调控线粒体自噬防治神经退行性疾病的可能机制，以期进一步丰富针灸防治神经退行性疾病机制的内涵。     

Screening of antioxidant activity of three Indian medicinal plants,traditionally used for the management of neurodegenerative diseases

A number of Indian medicinal plants have been used for thousands of years in the traditional system of medicine (Ayurveda). Amongst these are plants used for the management of neurodegenerative diseases such as Parkinson's, Alzheimer's, loss of memory, degeneration of nerves and other neuronal disorders by the Ayurvedic practitioners. Though the etiology of neurodegenerative diseases remains enigmatic, there is evidence, which indicates that defective energy metabolism, excitotoxicity and oxidative damage may be crucial factors (Ann. Neurol. 38 (3) (1995) 357). The part of the Ayurvedic system that provides an approach to prevention and treatment of degenerative diseases is known as Rasayana, and plants used for this purpose are classed as rejuvenators. This group of plants generally possesses strong antioxidant activity (Pharmacol. Biochem. Behav. 43 (1992) 1175), but only a few have been investigated in detail. In the present study, three such rasayana plants were tested for the first time for their toxicity and free radical scavenging activity both in vitro and ex vivo. All the three plant infusions (up to 1 mg/ml) showed no toxic effects on the viability of PC12 cell line as judged by MTT-test. Both ethanolic extracts and water infusions of the plants were tested for their antioxidant activity in the 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS*(+)) radical cation decolorization assay; inhibition of lipid peroxidation by plant infusions was carried out using spontaneous lipid peroxidation of rat brain homogenate, and IC50 values were determined. The results from the ABTS assay showed that the ethanolic extract of Sida cordifolia was found to be most potent (IC50 16.07 microg/ml), followed by Evolvulus alsinoides (IC50 33.39 microg/ml) and Cynodon dactylon (IC50 78.62 microg/ml). The relative antioxidant capacity for the water infusions was observed in the following order: E. alsinoides (IC50 172.25 microg/ml)>C. dactylon (IC50 273.64 microg/ml)>S. cordifolia (IC50 342.82 microg/ml). The results of water infusions of the plants on lipid peroxidation were as follows: E. alsinoides (IC50 89.23 microg/ml)>S. cordifolia) (IC50 126.78 microg/ml)>C. dactylon (IC50 608.31 microg/ml).