Network Pharmacologic Analysis and Experimental Verification of Atractylodes Macrocephala-Cistanche Deserticola in the Treatment of Constipation
The aim of this study was to explore the effect and mechanism of Atractylodes Macro-cephala-Cistanche Deserticola on constipation through network pharmacology and animal experi-ments.The constituents and corresponding target proteins of Atractylodes Macrocephala-Cistanche Deserticola were obtained from TCMSP database,and constipation related targets were obtained from GeneCards,OMIM and other databases.After the genes were sorted into UniProt database,softwares including Venny2.1.0,Cytoscape3.7.2 and STRING were used to draw Venn diagram and protein-protein interaction(PPI)network,and then CentiScaPe 2.2 plug-in was used for analysis.Bioinformatics GO analysis and KEGG signaling pathway enrichment anal-ysis were conducted through DAVID database.Some components with more potential targets and core targets were verified by molecular docking with AutodockTools and PyMOL.Forty mice were randomly divided into blank group(6 mice)and loperamide hydrochloride group(34 mice),which were gavaged with distilled water and 10.0 mg·kg-1 loperamide hydrochloride,respective-ly.After successful modeling,30 mice with constipation were evenly distributed into model group,positive control group and high-,medium-and low-dose drug groups.Blank group and model group were intragastric with distilled water,positive control group was intragastric with 10.0 mg·kg-1 moxapride citrate,and high-,medium-and low-dose groups were intragastric with 4.8,2.4 and 1.2 g·kg-1 Atractylodes Macrocephala-Cistanche Deserticola suspension,respec-tively,once a day for 7 days.Seven days later,the bowel movement and small bowel movement tests were performed.The results showed that PTGS2 was the most highly connected target gene.A total of 19 core targets for the treatment of constipation including AKT1,TNF and IL-6 were screened out.KEGG enrichment analysis showed that lipid and atherosclerosis and hepati-tis B pathways were more critical.Molecular docking results showed that the components with more potential targets in Atractylodes Macrocephala-Cistanche Deserticola had a good combina-tion with the core targets of constipation.Animal experiments showed that compared with the model group,the time of first melena was significantly shortened and the small bowel propulsion rate was significantly increased in the medium-and high-dose drug groups.Atractylodes Macro-cephala-Cistanche Deserticola can improve slow transit constipation.A variety of active ingredi-ents may regulate multiple signaling pathways to treat constipation through key targets such as PTGS2,AKT1,TNF and IL-6.
万方数据
维普
