Chemical composition and mechanism of action of Shenshuai Xiezhuo Decoction based upon UPLC-Q-TOF-MSE plus network pharmacology and molecular docking for treating chronic kidney disease with atherosclerosis
OBJECTIVE To detect the main active ingredients of Shenshuai Xiezhuo Decoction(SSXZ)and predict the mechanism of action and key targets of SSXZ for chronic kidney disease(CKD)with atherosclerosis(AS).METHODS High-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MSE)and traditional Chinese medicine system pharmacology database and analysis platform/bioinformatics analysis tool for traditional Chinese medi-cine molecular mechanism(TCMSP/BATMAN-TCM)were employed for examining the main active ingredients and target information of SSXZ.Disease targets were screened through online human Mendelian genetics(OMIM),gene disease association database(DisGeNET)and human gene comprehensive database(GeneCards),intersecting with drug targets for obtaining poten-tial targets,constructing a"traditional Chinese medicine active ingredient target"network,using protein/gene interaction database(String)database for constructing a protein interaction network(PPI).Gene Ontology(Go)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were utilized for elucidating potential mechanisms of action.Finally molecular docking was verified between the core components of traditional Chinese medicines and key targets.RESULTS UPLC-Q-TOF-MSE yielded 33 active ingredients and 75 active ingredients from database search.There were 349 drug ingredient targets,4,241 disease targets and 249 intersection targets.The core active ingredients such as quercetin,kaempferol,β-sitosterol,lignocerol,isorhamnetin and the core targets of protein kinase 1(AKT1),mitogen-activated protein kinase 3(MAPK3)and signal transducer and activator of transcription 3(STAT3)were obtained;A total of 1,292 entries were obtained from GO analysis.KEGG indicated that potential targets were clustered largely in PI3K-AKT pathway,lipid and atherosclerosis pathway and AGE-RAGE signaling pathway corre-lated with diabetic complications.Molecular docking revealed that the core components conjugated well with key targets.CONCLUSION The active components of SSXZ may regulate inflammation,oxidative stress,lipid metabolism and other mechanisms through interfering with MAPK3,AKT1,STAT3 and other targets for CKD As.And PI3K/Akt may be an impor-tant regulatory pathway.
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