Abstract:Objective: To investigate the potential mechanism of total glycosides of Cistanche deserticola Y. Ma on inflammatory bowel disease (IBD) through network pharmacology and animal experiments. Methods: The three dimensional structures of 7 main active components in total glycosides were collected by Pubchem database and literature. PharmMapper, UniProt, GeneCards and other databases were used to obtain the information of active ingredient related targets and IBD related gene targets. Then, the targets of Cistanche's active ingredients and IBD were mapped by Wayne diagram to obtain the intersection targets, and the intersection targets were uploaded to the String database for protein-protein interaction (PPI) screening analysis. Cytoscape 3.8.0 software was used to construct the ‘active component-target-pathway network’ for gene ontology (GO) functional enrichment and KEGG pathway enrichment analysis on the targets of the protective effect of total glycosides on IBD. To predict the target and pathway of total glycosides in the treatment of IBD, and construct mice model of IBD for further verification. Results: There were 254 protective targets of total glycosides against IBD, and 30 core targets were selected by PPI analysis. GO functional enrichment and KEGG pathway enrichment showed that total glycosides may play a role by regulating cancer pathway, mTOR pathway, TGF-β pathway, JAK-STAT pathway, AMPK pathway, etc. Then it affected cell signal transduction, proliferation, differentiation, and apoptosis. The results of animal experiments showed that total glycosides could effectively relieve weight loss and fecal bleeding in IBD mice, reduce disease activity index, and effectively inhibit the expression of mTOR and TGF-β in spleen. By sequencing 16S rDNA amplicon of mouse feces and annotating PICRUSt2 gene function, it was found that total cistanche glycosides regulate IBD disease and cell wall/membrane/envelope biogenesis in mice. Lipid metabolism, glucose metabolism and related defense signal transduction mechanism were closely related, which was consistent with the results of network pharmacology. Conclusion: Total glycosides could effectively treat IBD through multi-component, multi-target and multi-pathway synergism, which provided a new method and new idea for elucidating the clinical application of Cistanche in the treatment of IBD. However, its specific mechanism and material basis need to be verified by further experimental studies.