Pathway-pathway network-based study of the therapeutic mechanisms by which salvianolic acid B regulates cardiovascular diseases |
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Authors: | Li Ye Yuan He Hao Ye XuePing Liu LinLin Yang ZhiWei Cao KaiLin Tang |
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Institution: | (1) State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology, Shanghai, 200237, China;(2) Shanghai Center for Bioinformation Technology, Shanghai, 200235, China;(3) Department of Periodontology & Oral Medicine, School of Stomatology, Tongji University, Shanghai, 200092, China;(4) School of Life Science and Technology, Tongji University, Shanghai, 200092, China; |
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Abstract: | Investigation of the potential therapeutic mechanisms of drug candidates is an essential step in the process of new drug discovery.
With the rapid development of systems biology, recent network analyses of proteins, drugs, and diseases have enabled great
progress in delineating the molecule mechanisms of drug candidates. However, most analyses perform a direct association between
gene/protein and disease levels without considering the intermediate biological pathways regulated by the drugs. Given that
a protein performs its biological roles through pathways, we propose using a novel pathway-pathway network analysis to investigate
the potential therapeutic functions of the drug candidates. Many studies have demonstrated that salvianolic acid B (Sal B)
of Salvia miltiorrhiza is an effective therapy for cardiovascular diseases (CVD). Using molecular docking methods to identify direct interacting
targets of Sal B, we collected all Sal B-regulated proteins with supporting experimental evidence in PubMed abstracts. FDA-approved
CVD drugs and their corresponding targets were also collected. From a traditional drug-protein network analysis, we found
that Sal B could affect ACE and REN of the renin-angiotensin-aldosterone system to relax vessels and alleviate hypertension.
Subsequent pathway-pathway network analysis was attempted to study the mechanisms of Sal B in treating CVD, and demonstrated
that Sal B regulates immunity/inflammation, apoptosis, ion transport and basic metabolism processes in the treatment of CVD.
Regulating the immune/inflammation process may be the major mechanism of Sal B. We believe that pathway-pathway network analysis
is a novel method for studying the therapeutic mechanisms of herbal ingredients. |
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Keywords: | cardiovascular diseases salvianolic acid B network analysis biological pathway network module analysis |
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