文献类型：期刊文献

英文题名：Mechanistic role of gut microbiota metabolites in hypertension-insomnia comorbidity via integrated network pharmacology and molecular dynamics

作者：Ma, Rui-Ling[1];Kou, Yu-Shun[1];Wang, Yi-Yuan[1];Wang, Hong[1];Shen, Lu-Fan[1];Li, Bin[1];Zhang, Ling-Na[1];Li, Jia-Wei[1];Yi, Lin[1]

第一作者：马睿玲

通信作者：Yi, L[1]

机构：[1]Gansu Univ Tradit Chinese Med, Coll Integrated Tradit Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学中西医结合学院

通信机构：[1]corresponding author), Gansu Univ Tradit Chinese Med, Coll Integrated Tradit Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China.|[10735ed249c6606940a33]甘肃中医药大学中西医结合学院;[10735]甘肃中医药大学;

年份：2026

卷号：16

期号：1

外文期刊名：SCIENTIFIC REPORTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001758607800006)】；

基金：This work was supported by the following funding sources: National Natural Science Foundation of China (82160842) ; Gansu Provincial Natural Science Foundation (24JRRA1019); Gansu Provincial Joint Research Fund-General Program (23JRRA1521); Innovation Fund for University Faculty of Gansu Provincial Department of Education (2026A-112,2025A-111); Scientific Research and Innovation Fund of Gansu University of Chinese Medicine (2022KCYB-5).

语种：英文

外文关键词：Hypertension; Insomnia; Gut microbiota metabolites; Molecular dynamics simulation; Network pharmacology

摘要：Hypertension and insomnia frequently co-occur, yet their molecular link is unclear. Recent studies indicate that gut microbiota metabolites significantly influence neuroimmune and cardiovascular interactions. This research aimed to explore the role of these gut microbiota derived metabolites in the co-occurrence of hypertension and insomnia through an integrative network pharmacology approach. We extracted 278 gut microbial metabolites and their targets from the gutMGene database. Target prediction was performed using SEA and Swiss Target Prediction. We compiled 13,700 hypertension and 502 insomnia disease-associated targets from six databases, identifying 408 common targets. The 18 core targets were validated through PPI network analysis, KEGG pathway enrichment, and molecular docking. Ligand-target interaction stability was tested with 100 ns molecular dynamics simulations. Drug-likeness and toxicity were assessed using SwissADME and ADMETlab2.0. The PPI network analysis highlighted IL6 and PPARG as key hubs, each with 12 connections. KEGG pathway enrichment pinpointed the IL-17 signaling pathway as crucial, linking it to lipid metabolism and neuroinflammation. Molecular docking showed 3-indolepropionic acid binds strongly to IL6 (Vina score: -5.472 kcal/mol), supported by stable molecular dynamics simulations. Drug-likeness screening identified butyrate and 3-indolepropionic acid as promising, with no hepatotoxicity or cardiotoxicity. The MMTS network analysis emphasized Lacticaseibacillus paracasei as a major regulator of IL-17 signaling pathways. This study highlights the role of the microbiota-metabolite-inflammation axis in hypertension and insomnia comorbidity, suggesting IL-17 inhibition and microbial metabolite supplementation as treatments. It provides a theoretical framework and potential targets for developing gut-derived metabolite-based interventions for hypertension-insomnia comorbidity.