Prediction of active ingredients and potential mechanisms of Alisma decoction against atherosclerosis:A study based on UHPLC-Q-Orbitrap-HRMS and network pharmacology

Background:Atherosclerosis(AS)has been a potentially life-threatening disease worldwide.Alisma decoction(AD)is a famous Chinese formula in treating AS.However,the active components and potential mechanisms remain unknown.Methods:In this study,the active compositions of AD were analyzed by ultrahigh-performance liquid chromatography quadrupole-orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap-HRMS).The putative targets were predicted and interpreted by a series of bio-informative tools such as Venn,STRING,NetworkAnalyzer,ClusterMarker,and DAVID.Finally,the results were validated by molecular docking using AutoDock.Results:The results showed that alisol A,alisol B,23-o-Acetylalisol B,atractylenolideⅢand atractylenolideⅡwere the major compositions in AD.Thirty targets mainly distributed in three gene clusters were obtained after topological and cluster analysis.KEGG and GO analyses showed that genes in cluster 1 mainly participated in adipocytokine signaling pathway and played an important role in lipid metabolism,while genes in cluster 2 had regulatory actions via cAMP signaling pathway and may protect vascular function from AS,and genes in cluster 3 were closely related to inflammation.Furthermore,RXRA,AGT and CXCL8,the central gene of cluster 1,2 and 3,were verified to be strong binding with some major compositions in AD.Conclusion:The possible mechanisms of AD in the treatment of AS may be closely correlated with the regulation of lipid metabolism,vascular physiology and inflammation.Our study provided a new insight into the anti-AS effect of AD,but more pharmacological experiments should be performed for verification in the future.