Integrated strategy for biomarkers of stable coronary heart disease with phlegm and blood stasis syndrome based on RNA-seq and network pharmacology / 中国中药杂志

This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).

Exploration on biological networks relationship between effects of Danlou Tablets on cardiovascular disease and their relative components / 中草药

By systematically searching through the literature databases, such as PubMed, China National Knowledge Infrastructure (CNKI), and WanFang database and applying Ingenuity Pathway Analysis (IPA) software, we have identified the potential disease targets and forecasted the possible mechanisms of several chemical components in Danlou Tablets. We found that the pharmacological study on Danlou Tablets in recent years mainly focused on hyperlipidemia and atherosclerosis. And some of the identified chemical components have been shown to exert such effects through the cyclooxygenase 2 (PTGS2), leptin (LEP), nitric oxide synthase (NOS3), and low density protein receptor (LDLR). However, it remains a great challenge in identifying the key active chemical components of Danlou Tablets and elucidating their pharmacological effects. The combination of the chemical biology and network pharmacology approaches will facilitate our understanding on the cardiovascular disease specificity and mechanisms of the action for Danlou Tablets.