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米曲菌胰酶片治疗阿尔茨海默病的神经保护作用及其机制

Pharmacological Mechanisms Underlying the Neuroprotective Effects of Miq. on Alzheimer's Disease.

机构信息

Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.

出版信息

Int J Mol Sci. 2020 Mar 18;21(6):2071. doi: 10.3390/ijms21062071.

Abstract

Miq. (i.e., ), a traditional Chinese medicine, can exert neuroprotective effects in ameliorating mild cognitive impairment and improving the pathological hallmarks of Alzheimer's disease (AD). Here, 50 active compounds and 164 putative targets were collected and identified with 251 clinically tested AD-associated target proteins using network pharmacology approaches. Based on the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes pathway enrichments, the compound-target-pathway-disease/protein-protein interaction network constructions, and the network topological analysis, we concluded that may have neuroprotective effects by regulating neurotransmitter function, as well as brain plasticity in neuronal networks. Moreover, closely-related AD proteins, including the amyloid-beta precursor protein, the estrogen receptor 1, acetylcholinesterase, and nitric oxide synthase 2, were selected as the bottleneck nodes of network for further verification by molecular docking. Our analytical results demonstrated that terpene, as the main compound of extract, exerts neuroprotective effects, providing new insights into the development of a natural therapy for the prevention and treatment of AD.

摘要

密蒙花(Miq.)是一种中药,在改善轻度认知障碍和改善阿尔茨海默病(AD)的病理特征方面具有神经保护作用。在这里,使用网络药理学方法收集并鉴定了 50 种活性化合物和 164 种假定靶标,以及 251 种经临床测试的 AD 相关靶蛋白。基于基因本体论/京都基因与基因组百科全书通路富集、化合物-靶标-通路-疾病/蛋白质-蛋白质相互作用网络构建以及网络拓扑分析,我们得出结论,密蒙花可能通过调节神经递质功能以及神经元网络中的脑可塑性来发挥神经保护作用。此外,与 AD 密切相关的蛋白质,包括淀粉样前体蛋白、雌激素受体 1、乙酰胆碱酯酶和一氧化氮合酶 2,被选为网络的瓶颈节点,以便通过分子对接进一步验证。我们的分析结果表明,密蒙花提取物中的主要化合物——萜烯具有神经保护作用,为开发天然疗法预防和治疗 AD 提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89c4/7139528/4f92e7b4bdef/ijms-21-02071-g001.jpg

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