title: A network pharmacology study of Chinese medicine QiShenYiQi 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, QiShenYiQi (QSYQ), on myocardial infarction. QSYQ is composed of Astragalus membranaceus (Huangqi), Salvia miltiorrhiza (Danshen), Panax notoginseng (Sanqi), and Dalbergia odorifera (Jiangxiang). 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 in ArrayTrack. 55 potential targets of QSYQ were identified, of which 14 were confirmed in CVD-related literatures with experimental supporting evidences. Furthermore, three sesquiterpene components of QSYQ, Trans-nerolidol, (3S,6S,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol and (3S,6R,7R)-3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol from Dalbergia odorifera T. Chen, were validated experimentally in this study. Their anti-inflammatory effects and potential targets including extracellular signal-regulated kinase-1/2, peroxisome proliferator-activated receptor-gamma and heme oxygenase-1 were identified. Finally, through a three-level compound-target-pathway network with experimental analysis, our study depicts a complex MOA of QSYQ on myocardial infarction.
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Leihong
authors.initials: L
authors.lastname: Wu
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Yecheng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Linli
authors.initials: L
authors.lastname: Wang
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D053263:Gene Regulatory Networks / Q000187:drug effects* / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy / Q000379:methods; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics
chemical_list: D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D047495:PPAR gamma; D012717:Sesquiterpenes; C528580:qishen yiqi; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3