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ObjectiveTo investigate the potential pharmacological mechanism of Xinmaikang tablets in the treatment of atherosclerosis cardiovascular disease by using network pharmacology and cell experimental validation. MethodThe components of Xinmaikang tablets were searched by BATMAN-TCM database and the active ingredients and potential targets were screened. The atherosclerosis related disease targets were searched in GeneCards and online mendelian inheritance in man（OMIM） disease databases. The therapeutic targets were obtained by mapping the intersection of the tablets and disease targets. Therapeutic targets were uploaded to STRING database to construct protein-protein interaction（PPI） network. Cytoscape software was used to create a "drug-active component-therapeutic target" network map， and a network topology algorithm was used to screen key action targets. David software was used for gene ontology（GO） and Kyoto encyclopedia of genes and genomes（KEGG） function enrichment analysis. The key targets of drug therapy were validated by in vitro cell assay. ResultA total of 19 active ingredients， 132 potential targets and 4703 atherosclerotic disease-related target genes of Xinmaikang tablets were retrieved and screened， and 84 intersection targets were obtained. 3 key therapeutic targets of Xinmaikang tablets in the treatment of atherosclerotic diseases were screened， including Calmodulin 1（CALM1）， voltage-dependent L-type calcium channel subunit alpha-1C（CACNA1C） and Phosphatidylinositol 4，5-bisphosphate 3-kinase catalytic subunit alpha isoform（PIK3CA）. A total of 313 biological processes， 89 molecular functions and 53 cell components were obtained by GO enrichment. A total of 40 pathways were obtained from KEGG functional enrichment， including purine metabolism， renin secretion， CGMP/PKG signaling pathway and so on. In vitro cell experiment results verified that Xinmaikang tablets can up-regulate the expression of CALM1 and CACNA1C， down-regulate the expression of PIK3CA， so as to inhibit the activity of inflammatory response， and play a therapeutic role in atherosclerotic diseases. ConclusionXinmaikang tablets may treat atherosclerosis cardiovascular disease through betulin， methyleugenol and other compounds， through purine metabolism， renin secretion， cGMP/PKG signaling pathway and other pathways， which acts on CALM1， CACNA1C， PIK3CA and other targets.
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OBJECTIVE：To explore t he mechanism of Xinmaikang improving atherosclerosis （AS）in rabbits. METHODS ：A total of 50 male Zealand rabbits were randomly divided into sham operation group ，model group ，simvastatin group [positive control ， 2.60 mg/（kg·d）] and Xinmaikang low-dose and high-dose groups [ 0.21，0.84 g/（kg·d）]，with 10 rabbits in each group. Rabbits in sham operation group were fed with ordinary diet ，and only femoral artery was separated and ligated ，and abdominal aortic endothelium was not strained ；the other groups were given high-fat diet and received abdominal aortic intimal balloon injury to induce AS model. Ten weeks after operation ，sham operation group and model group were given intragastric administration of normal saline ，and administration groups were given corresponding drug solution intragastrically （normal saline as solvent ）with the volume of 100 mL，once a day ，for consecutive 12 weeks. After last administration ，the pathological changes of abdominal aorta and inner wall in rabbits were observed in each group. The serum contents of triglyceride （TG），total cholesterol （TC），low density lipoprotein cholesterol （LDL-C），high density lipoprotein cholesterol （HDL-C），interleukin-6（IL-6）and IL- 1β were detected，and the contents and protein expression of Toll-like receptor 4（TLR4）and nuclear factor-κB p65（NF-κB p65）in abdominal aortic tissue were determined. RESULTS ：Compared with sham operation group ，the intima of abdominal aorta in model group was rich in lipids ，the thickness of vessel wall and plaque area were increased obviously ，and there was obvious vascular endothelial injury. The contents of TG ，TC，LDL-C，IL-6 and IL- 1β in serum，the contents and protein expression of TLR 4 and NF-κB p65 in abdominal aorta tissue were significantly increased ，while the content of HDL-C was decreased significantly （P＜0.05 or P＜ 0.01）. Compared with model group ，the lesion of rabbit abdominal aorta were alleviated ，and no obvious damage was found on the inner wall. The contents of TG ，TC，LDL-C，IL-6，IL-1β of Xinmaikang high-dose group and simvastatin group as well as the content of NF-κB p65 and protein expression of TLR4 and cnd- NF-κB p65 were improved significantly （P＜0.05 or P＜0.01）. CONCLUSIONS：Xinmaikang can improve AS in rabbits ， and its mechanism may be assicated with inhibiting the expression of TLR 4，NF-κB p65 and inhibiting inflammatory response.