Combining UHPLC-QE-MS mass spectrometry, network pharmacology and molecular docking technology to explore the mechanism of action of TQTMD in the treatment of acute ischemic stroke
Authors: Guo Hao-tian , Zhang Kai-Xin , Zhang Zun-lu , Wang Xiang-Ying , Wang Yi-Ran , Liu Zhen-Ling , Cui Wen-Qiang , Xu Xiang-qing 
Published: September 2024

Abstract

Acute ischemic stroke is characterized by high morbidity, disability, and mortality, which brings great burden to families and society.This article combined UHPLC-QE-MS mass spectrometry and network pharmacology approach to explore potential targets of TiaoQiTongMai Decoction(TQTMD) against acute ischemic stroke (AIS).UHPLC-QE-MS mass spectrometry was employed for the qualitative analysis of the chemical constituents of TQTMD. The obtained constituents were subjected to screening and data standardization, and subsequently utilized to construct the active ingredient-core target network of TQTMD through the use of Cytoscape 3.10.1. The AIS-related targets were collated from disease databases, and the intersection of the AIS-related targets and the targets of TQTMD were identified to obtain the core targets. Subsequently, GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment of target protein interaction networks were conducted. The targets were then subjected to further analysis, namely the construction of a target protein interaction network, followed by GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Finally, Autodocktools software was employed to perform molecular docking and visualization analysis of the core compounds and key core targets. Molecular docking and visualization of core compounds and key core targets were conducted using AutodockTools.A total of 335 active ingredients were detected by mass spectrometry TQTMD, and 63 active ingredients, corresponding to 281 targets, were finally obtained after de-emphasis and screening; the key active compounds were used to construct an active ingredient-core target network, and the key core compounds were obtained by screening according to the indexes of degree, betweenness and closeness. Five core compounds were progesterone, Luteolin, Emodin, Aloeemodin, and Magnolol; 3803 AIS disease targets were obtained; 201 intersecting core gene targets were obtained, and 11 core gene targets were screened out by the target protein interaction network (PPI), which were CTNNB1, SRC, ACTB, TP53, IL6, TNF, PTGS2, The results of GO enrichment analysis showed that the biological process of TQTMD mainly involves the negative regulation of cell signaling, hypoxia response, and apoptosis; the results of KEGG pathway enrichment analysis showed that the signaling pathways in which TQTMD plays a role mainly include PI3K-Akt signaling, MARK signaling, AGE-RAGE signaling, TQTMD, PI3K-Akt signaling, AGE-RAGE signaling, and TQTMD signaling pathway. MARK signaling pathway, AGE-RAGE signaling pathway, and TNF signaling pathway. Molecular docking showed that the potential therapeutic targets CTNNB1, SRC, IL6, TNF, AKT1, ALB, IL1B, PPARG showed good affinity with the active compounds.This article preliminarily explores the mechanism of action of TQTMD involved in the regulation of AIS through various inflammation- and apoptosis-related targets and pathways, which provides theoretical implications for clinical applications.