Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: 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 -80M-bM-^DM-^C refrigerator. Total RNA was extracted using TRIZol Reagent (Invitrogen) and purified using RNeasy Mini kit (QIAGEN), following manufacturersM-bM-^@M-^Y 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.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Xiaohui Fan

PROVIDER: E-GEOD-54134 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The study aimed to investigate the mechanisms of Jianxin (JX) granules, a Traditional Chinese Medicine formulation, in the treatment of heart failure (HF) using metabolomic profiling. The HF model was established by ligation of left coronary artery. The successfully modeled rats were randomly divided into three groups: the model group, the JX granules group, and Sacubitril/Valsartan (S/V) group. Four weeks after treatment, LV tissue samples were collected. Proteomics was used to identify the differentially expressed proteins and potential pathways. The differential expressed proteins (DEPs) were obtained with Tandem Mass Tags approach. As compared to the control group, 150 DEPs were identified in model rats, comprising 112 up-regulated and 38 down-regulated proteins. Notably, in the JX granules group, 25 DEPs were identified compared to the model rats, encompassing 18 up-regulated and 7 down-regulated proteins. In comparison with the control group, 228 DEPs in the JX granules group were obtained, which comprised of 128 up-regulated and 100 down-regulated proteins. As compared with the control group, BP in the model group was mainly enriched in humoral immune response, positive regulation of apoptotic cell clearance, and the response to metal ions; Meanwhile, CC was mainly related to contractile and stress fibers, actin filaments, and extracellular space; MF was mainly enriched in the serine-type peptidase activity, actin binding, and peptidase activity. Furthermore, DEPs indicated by KEGG analysis were primarily linked to pathways such as the complement and coagulation cascades, regulation of the actin cytoskeleton, and adrenergic signaling. In contrast to the model group, BP in JX granules group was primarily associated with processes involving nucleosome organization, chromatin assembly or disassembly, DNA conformation change and small molecule catabolic processes; CC was primarily related to the protein-DNA complex, mitochondrion, intracellular, nucleosome, cytoplasm; MF displayed significant enrichment in protein dimerization and homodimerization activity, catalase activity, chromatin and nucleosomal DNA binding. Considering KEGG enrichment information, DEPs in the JX granules group were mainly enriched in metabolic pathways and ribosome pathway. The key differential genes, such as triosephosphate isomerase 1 (TPI1), lactate dehydrogenase B (LDHB), pyruvate kinase M (PKM), protein kinase B (Akt), and lactate dehydrogenase A (LDHA) were identified. The vital pathways including carbon metabolism, the PI3K-Akt signaling pathway, pyruvate metabolism, and HIF-1α signaling pathway were obtained.

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

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