A network pharmacology study of Chinese Medicine QSYQ to reveal its underlying multi-compound, multi-target, multi-pathway mode of action

Chinese medicine is a complex system guided by traditional Chinese medicine (TCM) theories, which has proven to be especially effective in treating chronic and complex diseases. However, the underlying modes of action (MOA) are not always systematically investigated. Herein, a systematic study was designed to elucidate the multi-compound, multi-target and multi-pathway MOA of a Chinese medicine ,QSYQ, on myocardial infarction. Male Sprague Dawley rat model of myocardial infarction were administered QSYQ intragastrically for 7 days while the control group was not treated. The differentially expressed genes (DEGs) were identified from myocardial infarction rat model treated with QSYQ, followed by constructing a cardiovascular disease (CVD)-related multilevel compound-target-pathway network connecting main compounds to those DEGs supported by literature evidences and the pathways that are functionally enriched. Three conditions were compared with three replicates each: (1) sham, i.e. without left anterior descending coronary artery (LAD) ligation; (2) model, with LAD ligation; (3) QSYQ, with LAD ligation and treated with QSYQ intragastrically for 7 days, the dosage was 105.6 mg/kg once a day. Rats were sacrificed after 7 days of i.g. administration under 10% chloral hydrate anesthesia (300mg/kg). Three tissue samples on the border between infarct and non-infarct area were dissected from left ventricles of each group. The tissue samples were stored at -80℃ refrigerator. Total RNA was extracted using TRIZol Reagent (Invitrogen) and purified using RNeasy Mini kit (QIAGEN), following manufacturers’ protocols. RNA quality was evaluated using an Agilent 2100 Bioanalyzer and electrophoresis in 2% (w/v) agarose gels. Only RNA with RNA integrity numbers (RINs) greater than 7.0 and 28SrRNA/18S rRNA ratio greater than 0.7 was used for microarray analyses. Whole genome microarray analysis was performed using Affymetrix rat Genome 230 2.0 chips.