Abstract
Background: Tongxinluo (TXL) capsule, a polypharmacy derived from traditional Chinese medicine (TCM), has been widely used in coronary heart disease (CHD), while the underlying mechanism of TXL capsule is still unclear. The present study aimed at investigating the underlying mechanism of TXL acting on CHD patients and providing substantial evidence in molecular evidence by means of a network pharmacological analysis.Method: Active compounds and targeted genes of TXL were retrieved from TCM systems pharmacology (TCMSP) and TCM integrative database (TCMID). CHD and coronary artery disease were treated as search queries in GeneCards and Online Mendelian Inheritance in Man (OMIM) databases to obtain disease-related genes. Visualization of disease–targets network was performed under administration of Cytoscape software. Besides, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were administered. H9c2 cells were used to validate the predicted results in cardiomyocytes/reoxygenation model, and anti-inflammatory ability was examined.Results: A network of a total of 212 nodes and 1016 edges was obtained. Peptide and ubiquitin-like protein ligase binding occupied a leading position of GO enrichment. For KEGG analysis, fluid shear stress and atherosclerosis, as well as inflammation-related pathways were enriched. Cellular validation revealed the anti-inflammatory effect of β-sitosterol, eriodictyol, odoricarpin, and tirucallol as active compounds of TXL.Conclusion: Our study provided substantial molecular evidence that TXL capsule possessed the characteristics of multitargets with safe profile, and the main component is capable of regulating cytokine level in CHD patients.
Highlights
BackgroundTongxinluo (TXL) capsule, a polypharmacy derived from traditional Chinese medicine (TCM), has been widely used in coronary heart disease (CHD), while the underlying mechanism of TXL capsule is still unclear
Coronary heart disease (CHD), one of the most common cardiovascular diseases is caused by reduction in blood flow to cardiomyocyte owing to build-up of plaque in arteries of heart [1,2]
In order to obtain the chemical ingredients of components in TXL capsule, we performed a comprehensive search on traditional Chinese medicine (TCM) systems pharmacology database (TCMSP, https://tcmspw.com/tcmsp.php) and TCM integrative database (TCMID, https://www.megabionet.org/tcmid/) by using the following queries: Ginseng radix et rhizoma (Araliaceae; Chinese ginseng), Paeoniaeradixrubra (Paeoniaceae; Chinese peony), Ziziphispinosae semen (Rhamnaceae; jujube seed), Dalbergiaeodoriferae lignum (Dalbergia odorifera T.C.Chen; Huanghuali wood), Santalum album L. (Santalaceae; sandalwood), Olibanum (Burseraceae; Boswellia)(prepared), Borneolum (Blumea balsamifera DC.), Hirudo (Haemopidae, leech), Scorpio (Buthidae; Chinese scorpion), Scolopendra
Summary
Tongxinluo (TXL) capsule, a polypharmacy derived from traditional Chinese medicine (TCM), has been widely used in coronary heart disease (CHD), while the underlying mechanism of TXL capsule is still unclear. The present study aimed at investigating the underlying mechanism of TXL acting on CHD patients and providing substantial evidence in molecular evidence by means of a network pharmacological analysis. Method: Active compounds and targeted genes of TXL were retrieved from TCM systems pharmacology (TCMSP) and TCM integrative database (TCMID). CHD and coronary artery disease were treated as search queries in GeneCards and Online Mendelian Inheritance in Man (OMIM) databases to obtain disease-related genes. For KEGG analysis, fluid shear stress and atherosclerosis, as well as inflammation-related pathways were enriched. Cellular validation revealed the anti-inflammatory effect of β-sitosterol, eriodictyol, odoricarpin, and tirucallol as active compounds of TXL. Conclusion: Our study provided substantial molecular evidence that TXL capsule possessed the characteristics of multitargets with safe profile, and the main component is capable of regulating cytokine level in CHD patients. Accepted Manuscript online: 29 September 2020 Version of Record published: 13 October 2020
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