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Therapeutic effects of astragaloside IV on myocardial injuries: multi-target identification and network analysis.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (9), pp. e44938. Date of Electronic Publication: 2012 Sep 17. - Publication Year :
- 2012
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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.
- Subjects :
- Binding Sites
Cardiovascular Diseases pathology
Cytoprotection drug effects
Doxorubicin pharmacology
Drug Approval
Humans
Molecular Docking Simulation
Myocytes, Cardiac drug effects
Myocytes, Cardiac pathology
Protein Conformation
Reproducibility of Results
Saponins therapeutic use
Signal Transduction drug effects
Triterpenes therapeutic use
United States
United States Food and Drug Administration legislation & jurisprudence
Cardiovascular Diseases drug therapy
Cardiovascular Diseases metabolism
Computational Biology
Molecular Targeted Therapy
Protein Interaction Mapping
Saponins metabolism
Saponins pharmacology
Triterpenes metabolism
Triterpenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23028693
- Full Text :
- https://doi.org/10.1371/journal.pone.0044938