Based on Network Pharmacology and Experimental Verification to Explore the Mechanism of Yangxin Decoction Anti-atherosclerosis
Objective Based on network pharmacology and in vivo experiments,to explore the mechanism of Yangxin Decoction in treating arterial atherosclerosis.Methods In the network pharmacology part,TCMSP database is used to screen the drug active ingredients and corresponding targets of Yangxin Decoction,Gene Cards,DisGeNet,OMIM,TTD database is used to screen atherosclerosis disease targets,the Evenn platform for interactive mapping to obtain drug disease intersection targets.Cytoscape 3.7.2 software is used to build a drug active ingredient core target disease interaction network diagram,The intersection target points are imported into STRING database to obtain PPI network diagram,and the Cytascape software is used for visualization processing.The metascape v3.5 platform is used for GO and KEGG enrichment analysis,and the micro-signal platform is used for visualization processing.In vivo experiment:ApoE-/-mice established atherosclerosis animal models through high-fat diet.The model mice were randomly divided into model group(Model),low-dose Yangxin Decoction group(YXT-L),and high-dose Yangxin Decoction group(YXT-H).C57BL/6 mice were taken as the control group,YXT-L group and YXT-H group were respectively given 2.6 g·kg-1·d-1 and 5.2 g·kg-1·d-1 of Yangxin Decoction extract aqueous solution,and the control group and model group were given equal volume distilled water for 4 weeks.Oil red O staining was used to observe the plaque area of aortic sinus,and ELISA was used to detect serum IL-6 and IL-1β,Caspase-3,VEGF levels,TG,TC,LDL-C,HDL-C levels of blood lipids detected by automatic biochemical instrument,and NF-κB p65,TNF-α,IKKβ Protein expression of aorta detected by Western blot.Results Network pharmacology:105 active ingredients of Yangxin Decoction were screened out,including 535 corresponding targets,4921 atherosclerotic disease targets,162 drug disease intersection targets,and the top 10 targets include AKT1,TNF,IL-6,VEGFA,IL-1β,TP53,JUN,CASP3,PPARG,PTGS2.A total of 2224 items were obtained from and GO analysis,including 1946 biological processes,100 cell components and 178 molecular functions.A total of 216 signal pathways were obtained by KEGG signal pathway enrichment analysis,mainly involving fluid shear stress,atherosclerosis,NF-κB signaling pathway,cAMP signaling pathway,diabetes cardiomyopathy,cysteine and methionine metabolism,VEGF signaling pathway,calcium signaling pathway,etc.In vitro experiment:Yangxin Decoction reduces serum TG,TC,LDL-C in ApoE-/-atherosclerosis mice in a dose-dependent manner,increases HDL-C level,reduces aortic sinus plaque area,and reduces serum IL-6,IL-1β,Caspase-3 and VEGF level;Inhibition of aortic NF-κB p65,TNF-α,IKKβ Protein expression.Conclusion Yangxin Decoction may inhibit TNF-α/IKKβ/NF-κB signaling pathway plays an anti-atherosclerosis role by regulating lipid metabolism,inhibiting inflammatory reaction,regulating cell apoptosis,etc.
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