Explore Effective Constituents and Mechanism of Tingli Dazao Xiefeitang in Treatment of Heart Failure Based on Network Pharmacology and Mass Spectrometry / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the effective constituents and mechanism of Tingli Dazao Xiefeitang for the treatment of heart failure through network pharmacology and high resolution mass spectrometry technique as well as molecular docking technique. Method:Chemical components and potential targets in Descurainiae Semen Lepidii Semen and Jujubae Fructus were searched by referring to literature and BATMAN-TCM database. The disease targets were searched in GeneCards database with ''heart failure'' as the key word. STRING platform was used to construct protein-protein interaction（PPI） network based on common targets of drugs and disease. The network topology was analyzed by using Cytoscape 3.7.2 software to obtain the core targets eventually. Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis of the core targets was conducted through DAVID database to draw a network of “herb-compound-target-pathway”. Based on the results of the network pharmacology research above，high resolution mass spectrometry was used to analyze the decoction and confirm the selected active components. AutoDock 4.2.6 software was used for molecular docking verification of key active components and related targets. Result:A total of 85 components were obtained in Descurainiae Semen Lepidii Semen，and 49 components were obtained in Fructus Ziziphi Jujubae. A total of 1 078 drug targets and 1 549 disease targets were identified. After PPI analysis and network topology analysis，23 core targets and 33 active components were obtained，involving 19 signaling pathways （<italic>P</italic><0.05）. Mass spectrometry analysis results indicated that 18 components such as isovanillic acid，descuraininA and kaempferol-7-<italic>O-β-D</italic>-glucopyranoside were confirmed in decoction. Molecular docking analysis results indicated that 6 core components （degree value top 6），such as isovanillic acid，descurainin A and kaempferol-7-<italic>O-β-D</italic>-glucopyranoside，had good binding activity with silent information regulatory factor 1（SIRT1），interleukin（IL）1B，protein kinase B<italic>α</italic>（AKT1） and tumor necrosis factor（TNF）. The compound recipe for heart failure mainly involved mitogen-activated protein kinase（MAPK），hypoxia inducible factor-1（HIF-1），Mammalian target of rapamycin（mTOR） and other signaling pathways. Conclusion:This study preliminarily investigated the effective constituents and mechanism of Tingli Dazao Xiefeitang in the treatment of heart failure. It can provide references for the precise clinical medication and screening of quality control markers，as well as the discovery of active components in the treatment of heart failure.