A systems pharmacology approach to investigate the mechanisms of action of Semen Strychni and Tripterygium wilfordii Hook F for treatment of rheumatoid arthritis

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.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.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.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.