Abstract: 【Objective】 This study was aimed to predict the potential targets and mechanism of WU Shen venation smooth decoction in the treatment of atherosclerosis, so as to provide reference for the clinical application of WU Shen venation smooth decoction.【Method】 The anti-atherosclerosis active components and targets of WU Shen venation smooth decoction were screened through the database of Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP), the atherosclerosis targets were obtained by GeneCards and OMIM databases and standardized by UniProt database, and the intersection targets were obtained by R language script.Cytoscape 3.9.1 software was used to establish the drug-component-target network diagram and analyze the topology properties.Upload the intersection target protein-protein interaction (PPI) relationship network was obtained from STRING database, and GO function and KEGG pathway enrichment analysis were performed in DAVID platform.AopE^-/- male mice were used for experimental verification, HE staining was used to observe the aortic lesions.The levels of monocyte chemokine 1 (MCP-1), interleukin-6 (IL6), IL1B and tumor necrosis factor-α (TNF-α) were determined by ELISA.【Result】 There were 124 active ingredients in WU Shen venation smooth decoction, 112 target genes, 4 711 atherosclerotic targets, and 98 overlapping targets.Topology analysis showed that the key components of WU Shen venation smooth decoction in the treatment of atherosclerosis were quercetin, beta sitosterol, stigmasterol and mignonette.The core targets were prostaglandin-endoperoxide synthase 1 (PTGS1), steroid receptor coactivator 2 (NOCA2), monkey serine protease 1 (PRSS1), etc.In the GO enrichment analysis, biological processes obtained 321 items (P<0.01), mainly related to the response to lipopolysaccharide, tumor necrosis factor, fatty acid metabolism, etc.;Molecular function obtained 93 items (P<0.01), mainly related to membrane rafts, membrane microdomains, synaptic membranes, etc.;Cell component obtained 45 items (P<0.01), which mainly involved DNA-binding transcription factor binding, RNA polymeraseⅡ-specific DNA-binding transcription factor binding, and nuclear receptor activity.A total of 129 signaling pathways (P<0.01) were identified by KEGG enrichment analysis, such as cancer pathway, lipid and atherosclerosis pathway, fluid shear stress and atherosclerosis pathway, etc., and most of them were related to the regulation of immune inflammation and atherosclerosis.The results of four items of blood lipid showed that, compared with model group, the levels of cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in serum of mice in the drug group were decreased significantly (P<0.05), while HDL-C were increased (P>0.05).The results of HE staining showed that the aortic plaques, lipid infiltration and the number of foam cells in the treatment group were significantly reduced.The results of ELISA showed that under the action of drugs, the inflammatory factors MCP-1, IL6, IL1B and TNF-α in aortic tissue homogenate were significantly decreased (P<0.05).【Conclusion】 WU Shen venation smooth decoction could treat atherosclerosis through multiple components, multiple targets and multiple pathways, among which the active ingredients quercetin, β-sitosterol, stigmasterol and luteolin might have inflammatory control and immune regulation effects by acting on PTGS1, acetylcholinesterase(ACHE), adenosine (AR) and other targets.

Key words: WU Shen venation smooth decoction; network pharmacology; atherosclerosis; blood lipid; inflammatory cytokines