基于网络药理学和分子对接探讨三黄泻心汤治疗阿尔茨海默病的机制

doi:10.3976/j.issn.1002-4026.2023.05.003

摘要/Abstract

摘要：

运用网络药理学方法探讨三黄泻心汤治疗阿尔茨海默病(Alzheimer's disease, AD)的作用机制。利用中药系统药理学数据库与分析平台检索并筛选出三黄泻心汤的有效成分及作用靶点。通过GeneCards数据库检索并筛选出AD相关靶点,维恩图获取药物与疾病交集靶点。使用STRING数据库得到蛋白质-蛋白质相互作用( protein-protein interaction, PPI)网络信息。使用Cytoscape构建药物-有效成分-靶点-疾病网络与PPI网络图,通过DAVID数据库对共同靶点进行GO( gene ontology)和KEGG ( Kyoto encyclopedia of genes and genomes)分析。使用SYBYL-X 2.1.1软件进行分子对接验证。筛选出三黄泻心汤47个有效成分,71个药物与疾病交集靶点,主要活性成分为槲皮素、β-谷甾醇、汉黄芩黄素、黄芩新素、半枝莲种素、苏荠苎黄酮,核心靶点为IL-6、TNF、IL-1β、VEGFA、TP53。GO功能分析主要涉及药物反应、缺氧反应、细胞迁移的正向调节、一氧化氮生物合成过程的正调控等生物过程,KEGG分析主要涉及癌症通路、HIF-1信号通路、TNF信号通路等通路。分子对接结果显示,β-谷甾醇、半枝莲种素等核心成分,与TP53、IL-6等核心靶点之间有着较强的结合能力。初步阐释了三黄泻心汤可通过调节HIF-1、TNF等信号通路,从而抑制Aβ聚集与tau磷酸化、阻断乙酰胆碱酯酶活化、抑制炎症进而干预阿尔茨海默病。

关键词: 网络药理学, 分子对接, 阿尔茨海默病, 三黄泻心汤

Abstract:

The aim of this study was to investigate the mechanism of action of Sanhuang Xiexin Decoction in the treatment of Alzheimer's disease (AD) using a network pharmacology approach. The active ingredients and targets of the Sanhuang Xiexin decoction were examined and screened using the systematic pharmacology database and the analysis platform of traditional Chinese medicine. AD-related targets were retrieved and screened through Gene Cards database, and drug and disease intersection targets were obtained through through Venn diagram.The STRING database was used to obtain the network information of protein-protein interaction (PPI). The Cytoscape was used to construct drugs-active ingredients-target-disease network and PPI,and DAVID database was used to analyze common targets in gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG). Furthermore, the Sybyl-x 2.1.1 software was used for molecular docking validation. The screening yielded 47 active ingredients and 71 related targets. Herein,the main active ingredients were quercetin, β-sitosterol, wogonin, baicalein, rivularin, and moslosooflavone; and the core targets were IL-6,TNF,IL-1β,VEGFA,TP53.The GO function enrichment analysis predominantly involved biological processes including drug response, hypoxia response, positive regulation of cell migration,and positive regulation of nitric oxide biosynthesis.KEGG analysis mainly involved pathways such as cancer pathways, HIF-1 signaling pathways, and TNF signaling pathways.Molecular docking results showed the presence of a relatively strong binding ability between the core target and the core compounds, such as β-sitosterol and rivularin.This study preliminarily explained that the Sanhuang Xiexin Decoction can interfere with AD by modulating HIF-1, TNF, and other signaling pathways, thereby inhibiting Aβ aggregation and tau phosphorylation, blocking acetylcholinesterase activation, and suppressing inflammation.

Key words: network pharmacology, molecular docking, Alzheimer's disease, Sanhuang Xiexin decoction

中图分类号:

R285

王一帆, 张喆, 田财军. 基于网络药理学和分子对接探讨三黄泻心汤治疗阿尔茨海默病的机制[J]. 山东科学, 2023, 36(5): 19-26.

WANG Yifan, ZHANG Zhe, TIAN Caijun. Mechanism of Sanhuang Xiexin decoction in treatment of Alzheimer's disease based on network pharmacology and molecular docking method[J]. Shandong Science, 2023, 36(5): 19-26.

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来源	标记	化合物名称	中文名称
大黄	DH1	eupatin	泽兰黄醇
	DH2	rhein	大黄酸
	DH3	toralactone	决明内酯
	A	beta-sitosterol	β-谷甾醇
黄连	HL1	berberine	黄连素
	HL2	berberrubine	小檗红碱
	B	epiberberine	表小檗碱
	C	coptisine	黄连碱
	HQ1	acacetin	金合欢素
	HQ2	wogonin	汉黄芩素
黄芩	A	beta-sitosterol	β-谷甾醇
	B	epiberberine	表小檗碱
	C	coptisine	黄连碱