title: A systems pharmacology approach to investigate the mechanisms of action of Semen Strychni and Tripterygium wilfordii Hook F for treatment of rheumatoid arthritis.
abstract: BACKGROUND
  The angiogenesis control at the initiation of rheumatoid arthritis (RA) that mainly blocks the inflammatory cascades expects to attenuate the action of angiogenic mediators, synovial angiogenesis, and to partially reverse the erosive bone damage. Two typical Chinese herbs, Semen Strychni and Tripterygium wilfordii Hook F (TwHF) have been used as a remedy to treat RA since ancient time. However, their functioning mechanisms are still unknown. Thus it is necessary to exploit their underlying mechanism for the treatment of RA.
  
  
  METHODS
  This study was undertaken to analyze their underlying mechanism based on a systems biology platform. Firstly, active components of the two herbs were screened out from TcmSP database based on their OB and DL values. Then their potential targets were predicted by using Random Forest, Support Vector Machine, and validated via docking process. Finally, a network of compound-target was constructed.
  
  
  RESULTS
  In this work, 27 and 33 active compounds were screened out from Semen Strychni and TwHF, targeting 28 and 32 potential proteins, respectively. The results show that the two herbs modulate the angiogenesis mediators through both direct and indirect pathways, and 21 common targets shared by Semen Strychni and TwHF bear major responsibility for treating RA.
  
  
  CONCLUSIONS
  The underlying mechanism of Semen Strychni and TwHF in treatment of RA is through multiple targets interaction by their blocking of the angiogenesis mediator cascades. This may provide us a better understanding of the function of the two herbs for the treatment of RA, as well as a clue to unveil their possible treatment effects of other systemic diseases, and in this way, hopefully the screening models may facilitate the discovery of novel combined drugs.
authors.affiliation: Key laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China. Electronic address: yanli@dlut.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China.
authors.forename: Jinghui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China.
authors.forename: Yuanchun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Center of Bioinformatics, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Computer Information Science & Engineering, Systems Biology Lab, University of Florida-Gainesville, FL 32611, USA.
authors.forename: Sushing
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China.
authors.forename: Yinfeng
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong 999077, Hong Kong.
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.affiliation: Key laboratory of Industrial Ecology and Environmental Engineering (MOE), Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning 116024, PR China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001682:Biological Availability; D055808:Drug Discovery / Q000379:methods; D029541:Loganiaceae; D010600:Pharmacology / Q000379:methods; D008517:Phytotherapy; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D012639:Seeds; D049490:Systems Biology; D029757:Tripterygium
chemical_list: D020533:Angiogenesis Inhibitors; D010936:Plant Extracts
keywords: Angiogenesis; Chinese herbs; Rheumatoid arthritis; Semen Strychni; Tripterygium wilfordii Hook F