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1.成都中医药大学,成都 610075
2.甘肃中医药大学,兰州 730000
3.成都中医药大学 附属医院,成都 610075
Received:01 February 2022,
Published Online:20 April 2022,
Published:20 November 2022
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屈艳秦,陈金鑫,董秤均等.基于β淀粉样蛋白探讨中医药治疗阿尔茨海默病的研究进展[J].中国实验方剂学杂志,2022,28(22):231-238.
QU Yanqin,CHEN Jinxin,DONG Chengjun,et al.Treatment of Alzheimer's Disease with Traditional Chinese Medicine Based on β-amyloid: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(22):231-238.
屈艳秦,陈金鑫,董秤均等.基于β淀粉样蛋白探讨中医药治疗阿尔茨海默病的研究进展[J].中国实验方剂学杂志,2022,28(22):231-238. DOI: 10.13422/j.cnki.syfjx.20221324.
QU Yanqin,CHEN Jinxin,DONG Chengjun,et al.Treatment of Alzheimer's Disease with Traditional Chinese Medicine Based on β-amyloid: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(22):231-238. DOI: 10.13422/j.cnki.syfjx.20221324.
β
淀粉样蛋白(A
β
)在脑中的大量聚集被公认为是阿尔茨海默病(AD)的起始因素,其集聚主要由A
β
过量产生和清除障碍引起。随着现代研究的进展,学者们针对AD进行了广泛而深入的研究,除了临床上常用的改善认知功能症状的药物外,A
β
单克隆抗体(Aduhelm)在美国成功上市,或可延缓AD进程,这表明靶向A
β
可能是治疗AD的有效途径,但其价格昂贵,不良反应和禁忌证较多,不利于临床推广。而中医药具有多成分、多靶点、多通路的特点,安全性良好,可从抑制A
β
产生和聚集、促进其脑内清除等多方面调节脑内A
β
沉积水平,减轻神经毒性,防治AD。小檗碱、没食子酸、蛇床子素、半枝莲黄酮、还脑益聪方、涤痰汤可通过调促进
α
分泌酶、抑制
β
、
γ
分泌酶的活性和表达,减少A
β
产生;黄芩素、芦荟大黄素、没食子酸、姜黄素等可通过与A
β
的疏水结构及介导A
β
聚集的H键、盐桥和
β
折叠结构相互作用,抑制A
β
的聚集,促进其解聚,减轻A
β
对神经细胞的增殖抑制作用;姜黄素和白藜芦醇可促进小胶质细胞的骨髓细胞触发受体2等表达,促进小胶质细胞的迁移和吞噬A
β
,双叶内酯、开心散和姜黄素可上调脑啡肽、胰岛素降解酶等降解酶表达促进A
β
降解、京平尼苷、二氢丹参酮、双氢青蒿素、姜黄素可通过激活正常自噬或抑制异常自噬,于细胞内降解A
β
;环黄芪醇、当归芍药散、益智防呆方、苓桂术甘汤通过改善血脑屏障(BBB)完整性和通透性促进A
β
流出和抑制A
β
的流入,益智防呆方、血栓通可通过促进水通道蛋白4(AQP4)的极化,使A
β
经淋巴系统清除,减少脑中A
β
聚集,减轻或预防神经细胞损伤,改善认知功能。以上总结旨在为中医药对AD的临床治疗提供更充足的证据和思路。
The massive accumulation of
β
-amyloid
(A
β
) in the brain is believed to be the first pathological mechanism of Alzheimer's disease (AD), and the accumulation is mainly resulted from the overproduction and dysfunction in the clearance. Extensive and in-depth research has been carried out on AD. In addition to the drugs which are commonly used in clinical settings to improve cognitive function, A
β
monoclonal antibody aducanumab (Aduhelm) has been successfully marketed in the US, which may delay the progress of AD. Thus, it is a potential method for the treatment of AD to target A
β
, but it is expensive, with many adverse reactions and contraindications, which hinders the clinical promotion. Traditional Chinese medicine, featuring multiple components, multiple targets, multiple pathways, and high safety, can regulate the level of A
β
deposition in the brain, alleviate neurotoxicity, and prevent and treat AD by inhibiting the production and aggregation of A
β
and promoting the clearance in the brain. Berberine, gallic acid, osthole, scutellaria barbata flavonoids, Huannao Yicong decoction and Ditantang can promote α-secretase and inhibit the activity and expression of
β-
and
γ
-secretase, thus reducing production of A
β
.
Baicalein, aloe-emodin, gallic acid, and curcumin can suppress the aggregation of A
β
, promote its depolymerization, and reduce the toxic effect of A
β
on nerve cells by interacting with the hydrophobic structure of A
β
and the H bond, salt bridge, and
β
-sheet that mediate the aggregation of A
β
. Curcumin and
resveratrol can promote the expression of triggering receptor 2 in bone marrow cells of microglia and the migration and phagocytosis of A
β
in microglia. Bilobalide, Kaixinsan and curcumin can up-regulate the expression of encephalin-degrading enzyme and insulin degrading enzyme to promote A
β
degradation, and geniposide, dihydrotanshinone, dihydroartemisinin, and curcumin can degrade A
β
in cells by activating normal autophagy or inhibiting abnormal autophagy. Cycloastragenol, Danggui Shaoyaosan, Yizhi Fangdai formula and Linggui Zhugan decoction can promote the outflow of A
β
and inhibit the inflow of A
β
by improving the integrity and permeability of the blood-brain barrier (BBB). Yizhi Fangdai formula and Xueshuantong can promote the polarization of aquaporin 4(AQP4), allow A
β
to be cleared through the lymphatic system, and reduce the aggregation of A
β
in the brain, thereby relieving or preventing nerve cell damage and improving cognitive function. The above summary aims to provide more sufficient evidence and ideas for the clinical treatment of AD with traditional Chinese medicine.
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