Investigating the Impact of Aspartame on Ulcerative Colitis Through Network Toxicology and Molecular Docking.

Abstract

The aim of this study is to elucidate the impact of aspartame on ulcerative colitis (UC). The research methodology involved extracting aspartame-associated targets from the ChEMBL and STITCH databases, while potential UC-related targets were obtained from the OMIM and GeneCards databases. The STRING platform and Cytoscape software were utilized to identify key targets through which aspartame may exert its influence on UC. Comprehensive analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were conducted using the DAVID database. Furthermore, molecular docking simulations were employed to validate the binding interactions between aspartame and these key targets. A total of 297 targets associated with aspartame and 5968 targets related to UC were identified. Protein-protein interaction (PPI) analysis indicated that BCL2, ESR1, HSP90AA1, SRC, TNF, and CASP3 may serve as central targets through which aspartame affects UC. KEGG pathway analysis highlighted the involvement of pathways such as the C-type lectin receptor, sphingolipid, and VEGF signaling pathways. In molecular docking studies, a binding energy of less than -5.0 kcal mol^-1 is indicative of strong binding activity. The results of the molecular docking analysis demonstrated that aspartame exhibits a high binding affinity with proteins including BCL2, ESR1, HSP90AA1, SRC, TNF, and CASP3. These interactions suggest that aspartame may play a role in the initiation and progression of UC through multiple targets and signaling pathways. Nonetheless, given the complexity of in vivo environments, it is crucial to corroborate these molecular findings within biological systems. This study offers a theoretical foundation that now needs to be confirmed through experimental and clinical research.