Using Network Pharmacology and Molecular Docking Technology to Explore the Mechanism of Modified Pulsatilla Decoction in the Treatment of Ulcerative Colitis

Abstract

Objective: Using network pharmacology and molecular docking technology, our aim was to clarify the biological activity, key targets, and potential pharmacological mechanisms of modified Pulsatilla decoction (MPD) in the treatment of ulcerative colitis (UC). Materials and Methods: The main active ingredients of MPD were screened using the traditional Chinese medicine systems pharmacology platform. UC targets were obtained from the GeneCard, OMIM, DisGeNET, PharmGkb, and DrugBank databases. The common genes of MPD in the treatment of UC were identified by Venn diagram. The visual interactive network diagram of “active ingredient-target-disease” was constructed using the software Cytoscape. We used the STRING database to construct a protein–protein interaction network and analyze the correlation in protein interaction. We conducted gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for common genes using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database and R software. Subsequently, the molecular docking verification of ingredients and targets was conducted through Discovery Studio. Last, in vivo experiments were conducted to further verify the findings. Results: A total of 51 active ingredients were screened, involving 141 common genes. The top 5 ingredients in MPD were quercetin, β-sitosterol, luteolin, kaempferol, and stigmasterol. Pathways involved in the treatment of UC include the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, the interleukin-17 (IL-17) signaling pathway, the tumor necrosis factor (TNF) signaling pathway, viral infection-related signaling pathways, and some cancer pathways. Molecular docking showed that the important ingredients of MPD were well docked with mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine (AKT1), vascular endothelial growth factor-A (VEGFA), transcription factor AP-1 (JUN), and interleukin-6 (IL-6). Animal experiments showed that MPD could ameliorate the injury and colitis in dextran sulfate sodium (DSS)-induced colitic rats. MPD inhibited the expression of p-p38A and p-MLC in UC rats. Conclusions: MPD has the characteristics of a multisystem, multi-ingredient, and multitarget in the treatment of UC. The possible mechanisms include inhibition of inflammation, apoptosis, oxidation, and tumor gene transcription. MPD may have a protective effect in the treatment of UC.