Network pharmacology and molecular docking reveal zedoary turmeric-trisomes in Inflammatory bowel disease with intestinal fibrosis

Abstract

Background: Inflammatory bowel disease (IBD) is a complex chronic IBD that is closely associated with risk factors such as environment, diet, medications and lifestyle that may influence the host microbiome or immune response to antigens. At present, with the increasing incidence of IBD worldwide, it is of great significance to further study the pathogenesis of IBD and seek new therapeutic targets. Traditional Chinese medicine (TCM) treatment of diseases is characterized by multiple approaches and multiple targets and has a long history of clinical application in China. The mechanism underlying the effect of zedoary turmeric-trisomes on inducing mucosal healing in IBD is not clear.

Aim: To explore the effective components and potential mechanism of zedoary turmeric-trisomes in the treatment of IBD with intestinal fibrosis using network pharmacology and molecular docking techniques.

Methods: The chemical constituents and targets of Rhizoma zedoary and Rhizoma sanarum were screened using the TCMSP database. The GeneCards database was searched to identify targets associated with intestinal fibrosis in IBD. The intersection of chemical component targets and disease targets was obtained using the Venny 2.1 online analysis platform, and the common targets were imported into the STRING 11.0 database to construct a protein interaction regulatory network. A "zedoary turmeric-trisomes-chemical composition-target-disease" network diagram was subsequently constructed using Cytoscape 3.7.2 software, and the topological properties of the network were analyzed using the "Network Analysis" plug-in. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the common targets were performed using the DAVID 6.8 database to elucidate the mechanism of zedoary turmeric-trisomes in the treatment of IBD. Subsequently, molecular docking of the compounds and targets with the highest intermediate values in the "zedoary turmeric-trisomes-chemical composition-target-disease" network was performed using Sybyl-x 2.1.1 software.

Results: A total of 5 chemical components with 60 targets were identified, as well as 3153 targets related to IBD and 44 common targets. The protein-protein interaction network showed that the core therapeutic targets included JUN, MAPK14, CASP3, AR, and PTGS2. The GO enrichment analysis identified 759 items, and the KEGG enrichment analysis yielded 52 items, including the cancer pathway, neuroactive ligand-receptor interaction, hepatitis B, and the calcium signaling pathway, reflecting the complex biological processes of the multicomponent, multitarget and multipathway treatment of diseases with zedoary turmeric-trisomes. Molecular docking showed that the compound bonded with the target through hydrogen bond interactions and exhibited good docking activity.

Conclusion: This study identified the potential mechanism of action of zedoary turmeric-trisomes in the treatment of inflammatory bowel fibrosis using network pharmacology and molecular docking technology, providing a scientific basis for further expansion of their clinical use.

Keywords: Inflammatory bowel disease; Intestinal fibrosis; Molecular docking; Network pharmacology; Zedoary turmeric trisomes.

Figure 1

Venn diagram of the targets of zedoary turmeric-trisomes and intestinal fibrosis in inflammatory bowel disease.

Figure 2

Protein-protein interaction network construction and analysis. A: Protein-protein interaction (PPI) regulatory network diagram; B: PPI network topology analysis.

Figure 3

Visualization of the “zedoary turmeric-trisomes - chemical component - target - disease” regulatory network.

Figure 4

Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.

Figure 5

Molecular docking results. A: Ivy saponin and GABRA1; B: Beta-sitosterol and lPTGS2; C: Formononetin and CHRM1; D: Stigmasterol and PTGS1.