Network pharmacology used to decode potential active ingredients in Ferula assafoetida and mechanisms for the application to Alzheimer’s disease

Background:Alzheimer’s disease(AD)is a neurodegenerative disease that primarily manifests as progressive memory loss and cognitive impairment.Traditional herbal medicines may be helpful in the discovery of new anti-AD drugs.Studies have shown that Ferula assafoetida has neuroprotective and memory-enhancing effects,which may be beneficial for the treatment of AD.However,the combination of active ingredients and their mechanisms remain unclear.Therefore,we aimed to identify potential active ingredients in F.assafoetida and their mechanisms of action against AD by using network pharmacology.Methods:In our study,an integrated network pharmacological approach,that included adsorption,distribution,metabolism and excretion screening,target identification,network construction,topological analysis,gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis,and molecular docking,was used to predict the pharmacological material basis and potential mechanisms through which these ingredients may treat and prevent AD.Results:The results indicated that 12 key active ingredients,obtained by topological analysis(including farnesiferol a,conferol,farnesiferol b,ferulic acid,etc.),may be the primary pharmacological components that may ameliorate AD.The 2 key significant pathways identified are the cholinergic synapse signaling pathway(critical targets include ACHE,CHRM1,CHRM2,MAPK1,PIK3CA,PIK3CB,PIK3CD,and PIK3CG)and the AD signaling pathway(critical targets include APP,BACE1,GSK3B,MAPK1,NCSTN,NOS1,PSEN1).These critical targets are closely related to the regulation of three typical pathological features of AD[central nervous system(CNS)cholinergic hypofunction,amyloid-β(Aβ)plaques,and hyperphosphorylated tau proteins].Finally,14 critical targets in the 2 key significant pathways were validated by molecular docking analysis.Conclusion:F.assafoetida may be effective for alleviating AD symptoms,through multi-component,multi-target,and multi-pathway synergistic effects,associated with the multiple pathogenesis hypotheses of AD.Our study may provide certain clues for the further development and utilization of this natural herbal medicine.