大黄素治疗阿尔茨海默病的研究进展

谢 鹏宇, 王 子心, 侯 森, 范 雪, 侯 霞*
佳木斯大学基础医学院

摘要


本文聚焦大黄素在抗阿尔茨海默病(AD)方面的研究。大黄素作为极具潜力的天然化合物,能通过多机
制、多靶点发挥抗AD功效,包括调节神经递质系统,促进乙酰胆碱合成与释放以改善认知记忆;抑制β-淀粉样
蛋白(Aβ)聚集、调节相关激酶减少Tau蛋白过度磷酸化,减缓AD病理进程;具备抗氧化与抗炎能力,上调抗氧
化酶活性、降低氧化产物水平、抑制小胶质细胞过度活化、减少炎症因子释放;还能调节肠道菌群平衡,经脑肠轴
影响神经功能。然而,这些机制相互关联且目前对其联系研究不足,如氧化应激与炎症、神经递质调节与Aβ代谢
关系中大黄素的协同作用未深入探究。后续研究可借助基因编辑技术、AD转基因动物模型、系统生物学方法及加入
Nrf2抑制剂、p-NF-κB抑制剂等进行干预实验,深入解析大黄素抗AD机制网络,这将助力理解AD发病机制,为
AD治疗提供精准理论依据,推动大黄素及其他中药在AD治疗领域的研发,有效治疗AD,提升患者生活质量。

关键词


大黄素;阿尔茨海默病;肠道菌群

全文:

PDF


参考


[1]仲丽丽,赵秦妍,路鑫,等.阿尔茨海默病作用

机制研究进展与治疗[J].中医药学报,2023,51(11):

116-123.

[2]Li, Z., Bi, H., Jiang, H., et al. Neuroprotective effect

of emodin against A lzheimer's disease via Nrf2 signaling

in U251 cells and APP/PS1 mice[J]. Molecular medicine

reports,2021,23(2):108.

[3]Li, Q., Gao, J., Pang, X., et al. Molecular mechanisms

of action of emodin: as an anti-cardiovascular disease drug[J].

Frontiers in pharmacology,2020,11:559607.

[4]Zhang, Y., Pu, W., Bousquenaud, M., et al. Emodin

inhibits inflammation, carcinogenesis, and cancer progression

in the AOM/DSS model of colitisas sociated intestinal

tumorigenesis[J].Frontiers in oncology,2021,10:564674.

[5]吴丛宇,周悦,上官璐茜,等.大黄素的药理作

用机制研究进展[J].中国药科大学学报,2023,54(05):

634-643.

[6]刘雅楠,牛芬溪,刘悦,等.金属离子稳态失衡与

阿尔茨海默病[J].中国药理学通报,2022,38(01):9-12.

[7]翟明锋.老年鼠肠道菌群对自发性痫样放电及癫

痫发作阈值影响的巨噬细胞及小胶质细胞机制[D].安徽

医科大学,2023.

[8]Dou, K.X., Tan, M.S., Tan, C.C., et al. Comparative

safety and effectiveness of cholinesterase inhibitors and

memantine for Alzheimer's disease: a net work meta-analysis

of 41 randomized controlled trials[J].Alzheimer's Research &

Therapy, 2018,10(1):126.

[9]Saunders, I.T., Mir, H., Kapur, N., et al. Emodin

inhibits colon cancer by altering BCL-2 family proteins and cell

survival pathways[J].Cancer Cell I nternational, 2019, 19:98.

[10]Tong, H., Huang, Z., Chen, H., et al. Emodin

reverses gemcitabine resistance of pancreatic cancer celllines

through inhibition of IKKβ/NF-κB signaling pathway[J].

Onco Targets and therapy,2020,13:983-9848.

[11]Liu, J., Sun, Y., Zheng, H., et al. Emodin attenuated

the kidney damage of high-fat-diet micevia the upregulation

of glucagon-like peptide-1 receptor [J]. BioMed Research In

ternational.2021,2021:6662704.

[12]高丙鹏,田静,靳银山,等.大黄素通过调控

ROS和NLRP3炎症体通路改善草酸钙结晶诱导的肾

小管上皮细胞损伤[J].现代泌尿外科,2021,26(06):

525-528+540.

[13]龙丹丹,张清,占凯,等.大黄素对四氯化碳诱

导肝纤维化大鼠的干预作用[J].广西医学,2020,42(16):

2120-2124.

[14]戚运,陈苏宁.大黄素改善肠屏障机制研究进展[J/OL].中华中医药学刊,1-10.

[15]Raulin, A.C., Doss, S.V., Trottier, Z.A., et al.

ApoE in Alzheimer's disease: pathophysiology and therapeutic

strategies[J].Molecular Neurodegeneration,2022, 17(1):72.

[16]王英全,梁景宏,贾瑞霞,等.2020-2050年中

国阿尔茨海默病患病情况预测研究[J].阿尔茨海默病及相

关病,2019,2(01):289-298.

[17]Chen, Z.R., Huang, J.B., Yang, S.L., et al.

Role of cholinergic signaling in Alzheimer's disease[J].

Molecules,2022,27(6):1816.

[18]Singh, S.P., Gupta, D. Discovery of potential

inhibitor against human acetyl cholinesterase: a molecular

docking and molecular dynamics investigation[J].

Computational Biology and Chemistry,2017,68:224-230.

[19]Hampel, H., Mesulam, M.M., Cuello, A.C., et al.

The cholinergic system in the pathophysiology and treatment

of Alzheimer's disease[J].The Journal Of Prevention of

Alzheimer's Disease,2018,141(7):1917-1933.

[20]曾楚华,刘思文,王雨,等.固本健脑液通过

调节APP代谢途径对AD大鼠发挥神经保护作用[J].中药

材,2023,12(46):3097.

[21]O'Brien, R.J., Wong., P.C. Amyloid precursor

protein processing and Alzhei mer's disease[J].Annual Review

of Neuroscience,2011,34(1):185-204.

[22]苏梓南,李凯,张根发.阿尔茨海默病β淀粉样

蛋白沉积斑块和寡聚体致病假说及其面临的挑战[J].中华

老年多器官疾病杂志,2023,22:157.

[23]Perry, V.H., Teeling, J. Microglia and macrophages

of the central nervous system:the contribution of

microglia priming and systemic inflammation to chronic

neurodegeneration[J]. Seminars in Immunopathology, 2013,

35(5): 601-612.

[24]Cui, B., Zhang, S.L., Wang, Y.T., et al. Farrerol

attenuates β-amyloid-induced oxidative stress and

inflammation through Nrf2/Keap1 pathway in a microglia

cellline[J]. Biomedicine & Pharmacotherapy,2019.109:112-119.

[25]郭 美 娜.PGC-1α通 过 调 控VDR的 表 达 抑 制

氧化应激改善阿尔茨海默病的机制研究[D].江苏大学,

2021.

[26]Dong, Y.T., Cao, K., Tian, L.C., et al. Stimulation

of SIRT1 attenuates the level of oxidative stress in the brains

of APP/PS1 double transgenic mice and in primary neurons

exposed to oligomers of the Amyloid-β peptide[J]. Journal

of Alzheimer's Disease,2018,63(1):283-301.

[27]刘芳彤,樊浩楠,沈立新,等.细菌铁离子摄

取系统与宿主免疫[J].微生物学通报,2019,46(12):

3432-3439.

[28]Zhang, Y., Fan, B.Y., Pang, Y.L., et al.

Neuroprotective effect of deferoxa mine on erastininduced

ferroptosis in primary cortical neurons[J].Neural Re generation

Research, 2020, 15(8):1539-1545.

[29]刘雅楠,牛芬溪,刘悦,等.金属离子稳态失衡

与阿尔茨海默病[J].中国药理学通报,2022,38(01):

9-12.

[30]郭佳旗,魏颖鸿,张慧,等.早老素阿尔茨海默

病发病机制及基于神经递质治疗的研究进展[J].分子生物

医学,2021,27(19):3761.

[31]Martens,Y.A., Zhao, N., Liu C.C., et al. ApoE

cascade hypothesis in the athogenesis of Alzheimer's disease

and related dementias[J]. Neuron,2022,110(8): 1304-1317.

[32]陈雪梅,胡博,唐晓姝,等.紫苏籽油对小鼠肠

道微生物及抗氧化能力的影响[J].食品与发酵工业,1-10.

[33]Abelein, A. Metal binding of Alzheimer's amyloid-β

and it seffect on peptide self-assembly[J].Accounts of Chemical

Research,2023,56(19):2653-2663.

[34]宋博雅,刘军,郝琳.肠道菌群影响阿尔茨海默

病病理机制的研究进展[J].生理科学进展,2024,55(01):

28-33.

[35]杨璐,李庆华,许玲,等.粪菌移植对阿尔茨海

默病小鼠学习记忆能力的影响[J].郑州大学学报(医学

版),2017,52(06):702-706.

[36]王晶,郑加平.肠道菌群与神经退行性疾病相关

性研究进展[J].中国医药科学,2022,12(14):44-47.

[37]Evans, L., Price, T., Hubert, N., et al. Emodin

inhibited pathological cardiac hypertrophy in response

to angiotensin-induced hypertension and altered the gut

mcrobiome[J].Biomolecules.2023,13(9):1274.

[38]夏能银.大黄素抗阿尔茨海默病的作用及机制研

究[D].武汉轻工大学,2024.

[39]Velazquez, R., Ferreira, E., Knowles, S., et al.

Lifelong choline supplement ation ameliorates Alzheimer's

disease pathology and associated cognitive deficits by attenuating

microglia activation[J]. Aging Cell.2019, 18(6): 13037.

[40]杨梦艳,周小涛,张继川,等.小胶质细胞在阿

尔茨海默病中的作用及潜在的应用价值[J].中国病理生理

杂志,2023,39(10):1884-1890.


Refbacks

  • 当前没有refback。