title: In-silico prediction of drug targets, biological activities, signal pathways and regulating networks of dioscin based on bioinformatics.
abstract: BACKGROUND
  Inverse docking technology has been a trend of drug discovery, and bioinformatics approaches have been used to predict target proteins, biological activities, signal pathways and molecular regulating networks affected by drugs for further pharmacodynamic and mechanism studies.
  
  
  METHODS
  In the present paper, inverse docking technology was applied to screen potential targets from potential drug target database (PDTD). Then, the corresponding gene information of the obtained drug-targets was applied to predict the related biological activities, signal pathways and processes networks of the compound by using MetaCore platform. After that, some most relevant regulating networks were considered, which included the nodes and relevant pathways of dioscin.
  
  
  RESULTS
  71 potential targets of dioscin from humans, 7 from rats and 8 from mice were screened, and the prediction results showed that the most likely targets of dioscin were cyclin A2, calmodulin, hemoglobin subunit beta, DNA topoisomerase I, DNA polymerase lambda, nitric oxide synthase and UDP-N-acetylhexosamine pyrophosphorylase, etc. Many diseases including experimental autoimmune encephalomyelitis of human, temporal lobe epilepsy of rat and ankylosing spondylitis of mouse, may be inhibited by dioscin through regulating immune response alternative complement pathway, G-protein signaling RhoB regulation pathway and immune response antiviral actions of interferons, etc. The most relevant networks (5 from human, 3 from rat and 5 from mouse) indicated that dioscin may be a TOP1 inhibitor, which can treat cancer though the cell cycle- transition and termination of DNA replication pathway. Dioscin can down regulate EGFR and EGF to inhibit cancer, and also has anti-inflammation activity by regulating JNK signaling pathway.
  
  
  CONCLUSIONS
  The predictions of the possible targets, biological activities, signal pathways and relevant regulating networks of dioscin provide valuable information to guide further investigation of dioscin on pharmacodynamics and molecular mechanisms, which also suggests a practical and effective method for studies on the mechanism of other chemicals.
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshun South Road, Dalian, 116044, China. yinlianhong1015@163.com.
authors: Lianhong
authors: L
authors: Yin
authors: The First Affiliated Hospital of Dalian Medical University, Dalian, 116022, China. zheng_ll2009@126.com.
authors: Lingli
authors: L
authors: Zheng
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshun South Road, Dalian, 116044, China. Linaxu_632@126.com.
authors: Lina
authors: L
authors: Xu
authors: The First Affiliated Hospital of Dalian Medical University, Dalian, 116022, China. Jihongyao_361@163.com.
authors: Deshi
authors: D
authors: Dong
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshun South Road, Dalian, 116044, China. Xuhan2002zs@163.com.
authors: Xu
authors: X
authors: Han
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshun South Road, Dalian, 116044, China. Yanqi_1976@163.com.
authors: Yan
authors: Y
authors: Qi
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshun South Road, Dalian, 116044, China. Yanyanzhao_2009@126.com.
authors: Yanyan
authors: Y
authors: Zhao
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshun South Road, Dalian, 116044, China. Youweixu_1964@163.com.
authors: Youwei
authors: Y
authors: Xu
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshun South Road, Dalian, 116044, China. jinyongpeng2005@163.com.|Research Institute of Integrated Traditional and Western Medicine of Dalian Medical University, Dalian, 116011, China. jinyongpeng2005@163.com.
authors: Jinyong
authors: J
authors: Peng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D019295:Computational Biology / Q000379:methods; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D027742:Dioscorea / Q000737:chemistry*; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D053263:Gene Regulatory Networks; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy; D008517:Phytotherapy; D011485:Protein Binding; D051381:Rats; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; C019357:dioscin; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004144:Diosgenin