Liaoning University of Traditional Chinese Medicine, Shenyang, China.
The Third Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Medicine (Baltimore). 2024 Sep 6;103(36):e39569. doi: 10.1097/MD.0000000000039569.
Tongxie Yaofang (TXYF), a classical traditional Chinese medicine, is commonly used in China to treat ulcerative colitis (UC). The aim of this study was to integrate network pharmacology with molecular docking and molecular dynamics simulations to explore the mechanism of Tongxie Yaofang in the treatment of UC. The traditional Chinese medicine systems pharmacology database was used to retrieve the relevant chemical compositions of the herbs contained in TXYF. The DisGeNET, GeneCards, Online Mendelian Inheritance in Man, and Therapeutic Target Database databases were used to retrieve UC-related targets. To construct protein-protein interaction networks and screen for key targets, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses of the key targets of TXYF in the treatment of UC were performed using R 4.3.2 software. AutoDock Tools 1.5.7 was used for molecular docking. Molecular dynamics simulations of protein complexes and complexes of proteins with small-molecule ligands and eutectic ligands were carried out with Gromacs 2022 software. Network pharmacology analysis revealed that TXYF could act on UC through multiple targets and pathways. It may exert therapeutic effects mainly through the AGE/RAGE, TOLL, JAK/STAT, and Th17 signaling pathways. The possible targets of TXYF in the treatment of UC could be AKT1, BCL2, EGFR, HMOX1, HSP90AA1, and TGFβ1. Molecular docking analysis revealed that AKT1 had the highest binding energy (-10.55 kcal/mol). Molecular dynamics simulations revealed that the complexes formed by the AKT1 protein and the chemical compounds MOL001910 and MOL00035 had good stability and high binding strength. AKT1 may be the most critical target of TXYF in treating UC, and the key chemical components of TXYF in treating UC may include β-sitosterol (MOL000358) and 11alpha,12alpha-epoxy-3beta-23-dihydroxy-30-norolean-20-en-28,12beta-olide (MOL00 1910). This study revealed that TXYF may exert therapeutic effects on UC through multiple targets, multiple biological functions, and multiple signaling pathways. This study provides a new insight into the pharmacological mechanism of TXYF in treating UC.
通心消炎方（TXYF）是一种经典的中药，常用于治疗溃疡性结肠炎（UC）。本研究旨在通过网络药理学与分子对接和分子动力学模拟相结合的方法，探讨通心消炎方治疗 UC 的作用机制。采用中药系统药理学数据库和分析平台（TCMSP）检索通心消炎方中所含草药的相关化学成分。使用 DisGeNET、GeneCards、在线孟德尔遗传数据库（OMIM）和治疗靶点数据库（TTD）检索 UC 相关靶点。使用 R 4.3.2 软件对通心消炎方治疗 UC 的关键靶点进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析，构建蛋白质-蛋白质相互作用网络，并筛选关键靶点。采用 AutoDock Tools 1.5.7 软件进行分子对接。使用 Gromacs 2022 软件对蛋白质-配体复合物和共晶配体复合物进行分子动力学模拟。网络药理学分析表明，TXYF 可能通过多种靶点和途径作用于 UC。它可能主要通过 AGE/RAGE、TOLL、JAK/STAT 和 Th17 信号通路发挥治疗作用。TXYF 治疗 UC 的可能靶点可能是 AKT1、BCL2、EGFR、HMOX1、HSP90AA1 和 TGFβ1。分子对接分析表明，AKT1 的结合能最高（-10.55 kcal/mol）。分子动力学模拟表明，AKT1 蛋白与化学化合物 MOL001910 和 MOL00035 形成的复合物具有良好的稳定性和高结合强度。AKT1 可能是 TXYF 治疗 UC 的最关键靶点，TXYF 治疗 UC 的关键化学成分可能包括β-谷甾醇（MOL000358）和 11alpha，12alpha-环氧-3beta-23-二羟基-30-降齐墩果酸-20-烯-28,12beta-内酯（MOL001910）。本研究表明，TXYF 可能通过多种靶点、多种生物学功能和多种信号通路对 UC 发挥治疗作用。本研究为通心消炎方治疗 UC 的药理机制提供了新的见解。
