In Silico-Based Screen For Discovery Of Synergistic Drug Combinations From Herb Medicines:A Case Using Cistanche Tubulosa

Neuroinflammation is characterized by the elaborated inflammatory response repertoire of central nervous system tissue.The limitations of the current treatments for neuroinflammation are well-known side effects and unsatisfied effects in the clinical trials of monotherapy,however.Intriguing,drug combination therapies are promising strategies to overcome the compensatory mechanisms and off-target effects.However,in silico-based discovery of synergistic drug combinations among abundant compounds from herb medicines is rare.Encouraged by the successfully applied cases on decoding the underlying mechanisms of curing complex diseases historically,here,we move on to investigate the effective drug combinations based on system pharmacology among numerous ingredients from the herb: Cistanche tubulosa(SCHENK)R.WIGHT.Firstly,molecular database is conducted including 66 chemicals and the corresponding chemicials with no aglycone,then 63 potential bioactive compounds,the related 133 direct and indirect potential targets are screened out by Drug-likeness evaluation combined with drug targeting process.Secondly,Compound-Target network is built with compounds and targets to acquire the data set for predicting effective drug combinations.We list the top 10 drug combinations which are employed by the algorithm Probability Ensemble Approach(PEA),and Compound-Target-Pathway network is then constructed among 12 compounds of the drug combinations,targets,and pathways to unearth the corresponding pharmacological actions,experimental validation is further conducted for the combinations.Finally,an integrating pathway approach is developed to elucidate the therapeutic effects of the herb in different pathological features-relevant biological processes.Overall,the method may provide a productive avenue for developing drug combination therapeutics.