Systematic Investigation Of The Erigeron Breviscapus Mechanism For Treating Cerebrovascular Diseases

Cerebrovascular diseases(CBVDs),characterized by striking morbidity and mortality,have become one of the most threatening diseases for human beings,which are arousing more and more attention.The existing drugs of CBVDs target one or few pathogenic factors,which the efficacy is limited because of the complexity of diseases.Traditional Chinese medicine(TCM),featured by multi-component and multi-target endow the great effectiveness in CBVDs treatment.For instance,Erigeron breviscapus,Aster breviscapus Vant,has been used to treat CBVDs for long time and the efficacy has been verified through years' of practice.Nevertheless,the mechanisms of Erigeron breviscapus to treat the CBVDs are still unclear.To systematically decipher the Erigeron breviscapus mechanisms for CBVDs,the systems pharmacology approach is utilized by ADME pharmacokinetic screen,target fishing,and network analysis.Main results for this study are as follows:(1).First,14 potentially active molecules are screened out through in silico ADME pharmacokinetic evaluation,most of which have been reported with excellent biological activities.(2).Then 169 targets of active molecules are read out using our in-house software systems drug targeting(sys DT)and Weighted Ensemble Similarity(WES).(3).We find that component targets are significantly enriched to the CBVDs therapeutic targets by analyzing their biological processes and protein-protein interaction(PPI).(4).A multi-layer network analysis method including components-targets network,targets-pathways network and “CBVDs pathway” indicates the Erigeron breviscapus exerts protective effect on CBVDs via regulating multiple pathways and hitting on multiple targets.(5).Meanwhile in vitro experiments confirm that the stigmasterol,scutellarein and daucosterol from Erigeron breviscapus can treat CBVDs by increasing the MEK and PLC? proteins levels as well as decreasing the expression of Bax,PI3 K and eNOS,which led to the cell survival,proliferation and contraction.The approach used in this work offers a new exemplification for systematically understanding the mechanisms of herb medicine,which will give an impulse to the CBVDs drug development.