Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an, China.
Department of Pharmacy, Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Artif Cells Nanomed Biotechnol. 2024 Dec;52(1):145-155. doi: 10.1080/21691401.2024.2319827. Epub 2024 Feb 27.
Although the gut microbial metabolites exhibit potential effects on coronary heart disease (CHD), the underlying mechanism remains unclear. In this study, the active gut microbial metabolites acting on CHD and their potential mechanisms of action were explored through a network pharmacological approach. We collected a total of 208 metabolites from the gutMgene database and 726 overlapping targets from the similarity ensemble approach (SEA) and SwissTargetPrediction (STP) database, and ultimately identified 610 targets relevant to CHD. In conjunction with the gutMGene database, we identified 12 key targets. The targets of exogenous substances were removed, and 10 core targets involved in CHD were eventually retained. The microbiota-metabolites-targets-signalling pathways network analysis revealed that C-type lectin receptor signalling pathway, Lachnospiraceae, Escherichia, mitogen-activated protein kinase 1, prostaglandin-endoperoxidase synthase 2, phenylacetylglutamine and alcoholic acid are notable components of CHD and play important roles in the development of CHD. The results of molecular docking experiments demonstrated that AKT1-glycocholic acid and PTGS2-phenylacetylglutamine complexes may act on C-type lectin receptor signalling pathways. In this study, the key substances and potential mechanisms of gut microbial metabolites were analysed via network pharmacological methods, and a scientific basis and comprehensive idea were provided for the effects of gut microbial metabolites on CHD.
虽然肠道微生物代谢物对冠心病(CHD)具有潜在影响,但作用机制尚不清楚。本研究采用网络药理学方法,探讨作用于 CHD 的活性肠道微生物代谢物及其潜在作用机制。我们从肠道基因数据库中收集了 208 种代谢物,从相似性综合方法(SEA)和瑞士靶向预测(STP)数据库中收集了 726 种重叠靶点,最终确定了 610 种与 CHD 相关的靶点。结合肠道基因数据库,我们确定了 12 个关键靶点。去除外源性物质的靶点后,最终保留了 10 个与 CHD 相关的核心靶点。微生物群-代谢物-靶点-信号通路网络分析表明,C 型凝集素受体信号通路、lachnospiraceae、大肠杆菌、丝裂原活化蛋白激酶 1、前列腺素内过氧化物合酶 2、苯乙酰谷氨酰胺和醇酸是 CHD 的显著组成部分,在 CHD 的发展中发挥着重要作用。分子对接实验结果表明,AKT1-甘胆酸和 PTGS2-苯乙酰谷氨酰胺复合物可能作用于 C 型凝集素受体信号通路。本研究采用网络药理学方法分析了肠道微生物代谢物的关键物质和潜在机制,为肠道微生物代谢物对 CHD 的影响提供了科学依据和综合思路。