Network mechanism on effective constituents from Polygala Tenuifolia for anti-Alzheimer Disease

OBJECTIVE To clarify out the network pharmacology mechanism of Polygala tenuifolia against Alzheimer disease(AD).METHODS Firstly,we collected the chemical constituents from Polygala tenuifolia and key targets toward AD.Machine learning algorithms were applied to construct classifi.ers for predicting the effective constituents.Secondly,docking models were utilized for further evalua.tion.Finally,we built constituent-target,target-target network and target-biology pathway network.RE.SULTS 104 chemical constituents Polygala tenuifolia from were collected.Through prediction of bloodbrain penetration and validation,36 chemical constituents were selected among 100 chemical constitu.ents,their action targets mainly focused on AChE,COX-2,TNF-α,insulin-degrading enzyme and APP.Their main structure types include Polygala saponins,Polygala glycosides,Polygala shrubby ketones,polygala xanthones and sterols,which acted on AchE,APP,M-TAU,GSK3β and 5 HT1A with high fre.quency.Gene-Ontology and KEGG enrichment analysis showed that the main pathways of these con.stituents involve in neurotransmitter release,synaptic conduction and synaptic plasticity,apoptosis reg.ulation,phosphorylation pathway,Ca^(2+) signaling pathway,and so on.CONCLUSION This study uncov.ered a network mechanism of Polygala tenuifolia against Alzheimer disease,which may provide impor.tant information for the further study and new drug development.