title: Therapeutic effects of astragaloside IV on myocardial injuries: multi-target identification and network analysis.
abstract: Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb used for cardiovascular diseases (CVD). In this work, we investigated the therapeutic mechanisms of AGS-IV at a network level by computer-assisted target identification with the in silico inverse docking program (INVDOCK). Targets included in the analysis covered all signaling pathways thought to be implicated in the therapeutic actions of all CVD drugs approved by US FDA. A total of 39 putative targets were identified. Three of these targets, calcineurin (CN), angiotensin-converting enzyme (ACE), and c-Jun N-terminal kinase (JNK), were experimentally validated at a molecular level. Protective effects of AGS-IV were also compared with the CN inhibitor cyclosporin A (CsA) in cultured cardiomyocytes exposed to adriamycin. Network analysis of protein-protein interactions (PPI) was carried out with reference to the therapeutic profiles of approved CVD drugs. The results suggested that the therapeutic effects of AGS-IV are based upon a combination of blocking calcium influx, vasodilation, anti-thrombosis, anti-oxidation, anti-inflammation and immune regulation.
authors.affiliation: Department of Natural Medicinal Chemistry, College of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Yang
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Tao
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Yaocheng
authors.initials: Y
authors.lastname: Rui
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Cao
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019295:Computational Biology; D019610:Cytoprotection / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D017277:Drug Approval; D006801:Humans; D062105:Molecular Docking Simulation; D058990:Molecular Targeted Therapy; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D015203:Reproducibility of Results; D012503:Saponins / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence
chemical_list: D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D004317:Doxorubicin