OBJECTIVE To identify the chemical composition of Yindan Xinnaotong soft capsules(YDXNT) using the technique high-resolution mass spectrometry, together with the network pharmacology approach to explore the active ingredients and potential molecular mechanism of YDXNT for "simultaneous treatment of heart and brain disorders".
METHODS Drawing on the chemical composition of YDXNT as characterized by UHPLC Q-Exactive Plus Orbitrap HRMS, the active compounds were evaluated using the TCMSP and SwissADME databases. Compounds meeting the criteria for oral bioavailability≥30%, drug-likeness≥0.18, which got a “High” gastrointestinal absorption score, and the DL threshold with at least three “Yes” were selected. These active compounds were then subjected to potential target retrieval. Corresponding target genes linked to cardiovascular and cerebrovascular diseases were identified through comprehensive searches of the OMIM, DisGeNET, GeneCards, TTD and PharmGKB databases. The intersection targets of the two datasets between compounds and diseases were identified using Venny software. Subsequently, Cytoscape 3.9.1 and the STRING database were used for the analysis of the protein-protein interaction network and the construction of the "drug-active ingredient-target-disease" network, so as to pinpoint the core components and targets. Using the DAVID database, perform Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes Enrichment Analysis(KEGG) to predict the potential target genes of YDXNT in the treatment of cardiovascular and cerebrovascular diseases and predicting its mechanism. Finally, molecular docking simulations of the top five targets with the main active compounds was performed to corroborate the findings of the network pharmacology analysis.
RESULTS A total of 82 chemical components in YDXNT were identified, including flavonoids, organic acids, phenanthrene quinones, and diterpenoid lactones. Utilizing the TCMSP and SwissADME databases, thirty-four active compounds were selected, such as quercetin, isosakuratine, and dihydrotanshinone I, while obtaining 389 targets associated with these active compounds and 249 potential target genes relevant to cardiovascular and cerebrovascular disease treatment. GO and KEGG enrichment analyses indicated that active compounds of YDXNT primarily exert therapeutic effects on cardiovascular diseases through the regulation of pathways like lipid and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE, IL-17, PI3K-Akt, HIF-1, and TNF. Molecular docking results further confirmed the high affinity between STAT3 and HSP90AA1 with compounds such as dihydrotanshinone I, kaempferol, and lignocaine.
CONCLUSION This study preliminarily suggests that the mechanism underlying YDXNT's “simultaneous treatment of heart and brain disorders” may be associated with such factors as atherosclerosis, inflammation, apoptosis, and oxidative stress. These findings provide a scientific foundation for further analysis of the mechanism and clinical application.
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