Drug target identification using network analysis: Taking active components in Sini decoction as an example.
Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound.
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
Si
S
Chen
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
Hailong
H
Jiang
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
Yan
Y
Cao
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
Yun
Y
Wang
School of Pharmacy, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA, 15261, USA.
Ziheng
Z
Hu
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
Zhenyu
Z
Zhu
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China.
Yifeng
Y
Chai
D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D016571:Neural Networks, Computer; D011506:Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004365:Drugs, Chinese Herbal; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; C478756:sini tang