Ren Mengjiao, Ma Jian, Qu Minye
Department of Warm Disease, School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Medicine (Baltimore). 2024 Dec 13;103(50):e40929. doi: 10.1097/MD.0000000000040929.
Numerous studies have demonstrated a correlation between asthma and irritable bowel syndrome (IBS). The Chinese herbal compound Shaoyao Gancao Tang (SYGCT) has been found to have therapeutic effects on both asthma and IBS, but the underlying mechanisms are not yet fully understood. This study aims to explore the key components, key targets, and potential mechanisms of SYGCT in treating asthma with IBS by using network pharmacology, molecular docking techniques and molecular dynamics simulation.
The major chemical components and potential target genes of SYGCT were screened by bioinformatics. The key targets of Asthma-IBS comorbidity were identified based on network modules. The intersection of the drug targets and disease targets was identified as the potential targets of SYGCT in treating asthma-IBS. Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to identify the biological processes and signaling pathways involved in these potential targets. A protein-protein interaction network was constructed to identify hub targets, while a drug-compound-target topological network was built to screen key compounds. Molecular docking was used to verify the affinity between the hub targets and key compounds. Molecular dynamics analysis was utilized to assess the binding stability of these interactions.
Network pharmacology analysis revealed that the therapeutic effect of SYGCT on asthma-IBS involved multiple biological processes and signaling pathways. It may exert therapeutic effects primarily through signaling pathways such as IL-17, TNF, and Th17 cell differentiation. The possible targets of SYGCT in the treatment of asthma-IBS could be IL6, TNF, JUN, PTGS2, STAT3, IL1B, CASP3, NFKBIA, IL10, and PPARG. Molecular docking verification showed that the predicted targets had good binding affinity with the compounds, among which PTGS2, CASP3, and PPARG had higher binding energy. Molecular dynamics simulation revealed that PTGS2, CASP3, and PPARG proteins had good stability and high binding strength with the compounds 2-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[6,5-f]chromen-3-yl]-5-methoxyphenol and shinpterocarpin.
SYGCT plays a therapeutic role in asthma and IBS through multiple targets and pathways, providing a theoretical basis for explaining the mechanism and clinical application of SYGCT in treating different diseases with the same treatment in asthma and IBS.
大量研究已证实哮喘与肠易激综合征（IBS）之间存在关联。已发现中药复方芍药甘草汤（SYGCT）对哮喘和IBS均有治疗作用，但其潜在机制尚未完全明确。本研究旨在运用网络药理学、分子对接技术和分子动力学模拟，探索SYGCT治疗哮喘合并IBS的关键成分、关键靶点及潜在机制。
通过生物信息学筛选SYGCT的主要化学成分和潜在靶基因。基于网络模块确定哮喘 - IBS共病的关键靶点。将药物靶点与疾病靶点的交集确定为SYGCT治疗哮喘 - IBS的潜在靶点。进行基因本体功能注释和京都基因与基因组百科全书通路富集分析，以确定这些潜在靶点所涉及的生物学过程和信号通路。构建蛋白质 - 蛋白质相互作用网络以识别核心靶点，同时构建药物 - 化合物 - 靶点拓扑网络以筛选关键化合物。利用分子对接验证核心靶点与关键化合物之间的亲和力。运用分子动力学分析评估这些相互作用的结合稳定性。
网络药理学分析表明，SYGCT对哮喘 - IBS的治疗作用涉及多个生物学过程和信号通路。它可能主要通过IL - 17、TNF和Th17细胞分化等信号通路发挥治疗作用。SYGCT治疗哮喘 - IBS的可能靶点为IL6、TNF、JUN、PTGS2、STAT3、IL1B、CASP3、NFKBIA、IL10和PPARG。分子对接验证表明，预测靶点与化合物具有良好的结合亲和力，其中PTGS2、CASP3和PPARG具有较高的结合能。分子动力学模拟显示，PTGS2、CASP3和PPARG蛋白与化合物2 - [(3R) - 8,8 - 二甲基 - 3,4 - 二氢 - 2H - 吡喃并[6,5 - f]色烯 - 3 - 基] - 5 - 甲氧基苯酚和新异甘草素具有良好的稳定性和较高的结合强度。
SYGCT通过多个靶点和通路在哮喘和IBS中发挥治疗作用，为解释SYGCT在哮喘和IBS中同病异治的机制及临床应用提供了理论依据。
