Integrating single-cell sequencing and network pharmacology to reveal the mechanisms of matrine against ulcerative colitis

Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disease (IBD). The quinolizidine alkaloid matrine exhibits potent anti-inflammatory, immunomodulatory, neuroprotective, and anti-cancer properties. Using a computational biology approach integrating single-cell and bulk RNA sequencing data, network pharmacology, and molecular docking, this study aimed to elucidate the mechanisms underpinning matrine’s therapeutic actions against UC. The differentially expressed genes (DEGs) in UC were identified by bulk RNA sequencing (RNA-seq, GSE224758) data. Potential targets of matrine in UC treatment were identified by integrating these DEGs with potential target candidates of matrine, and their protein-protein interaction (PPI) and GO and KEGG enrichment analyses were performed. Cellular heterogeneity in UC was analyzed using single-cell RNA-seq (scRNA-seq, GSE214695) data. Putative hub genes were identified, and their binding mechanism to matrine was investigated by molecular docking. Network pharmacology identified 39 potential targets, primarily associated with IL-6 regulation and inflammatory responses, and highlighted key pathways including the TNF, AGE-RAGE, and IL-17 signaling. Single-cell atlas further delineated the cellular landscape, revealing significant alterations in epithelial and plasma cell populations in UC. The convergence of these analyses pinpointed CD44 and TIMP1 as potential hub targets, a finding supported by molecular docking simulations that demonstrated strong binding affinity between matrine and both CD44 (-8.4 kcal/mol) and TIMP1 (-7.2 kcal/mol) proteins. This study provides a comprehensive multi-omics and computational framework that elucidates the multi-target mechanism of matrine in UC treatment.