The Potential Mechanisms of Banxia Xiexin Decoction in Treating Chronic Colitis: Insights from UPLC-Q-TOF-MS/MS and Network Pharmacology Studies.

Abstract

Introduction: Banxia Xiexin Decoction (BXD)is commonly used to treat a variety of gastrointestinal disorders, including Chronic Colitis (CC), due to its anti-inflammatory, antibacterial, and intestinal flora-regulating effects. However, CC is a chronic intestinal immunologic disease whose exact pathogenesis is unknown. Thus, more studies are needed to clarify the mechanism of action of BXD for CC treatment.

Objective: The common components of BXD were validated by combining ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) analysis. Then, the mechanism of BXD for CC treatment was investigated using network pharmacology, including potential therapeutic CC phytochemicals, potential targets, and related signaling pathways. Molecular docking analysis was performed to investigate the protein-ligand interactions.

Materials and methods: Firstly, the chemical composition of BXD was determined by UPLC-QTOF- MS/MS technique and combined with TCMSP and HERB databases to determine the possible active ingredients in the formula, and the Uniprot database was used to find the targets corresponding to the ingredients; the disease targets related to CC were obtained by using GeneCards and Dis- GeNET databases. The intersection of component targets and disease targets was taken and imported into the STRING database for analysis, and then by Cytoscape 3.9.1 software, a protein-protein interaction network diagram (PPI) was constructed and the multi-level network of TCM-compoundtarget- disease was visualized, and DAVID database was used for GO and KEGG enrichment analysis of core genes. Finally, PyRx, AutoDockTools 1.5.6, PyMol 2.5.0, and Open Babel 2.4.1 were used for molecular docking, virtual computation, and visualization analyses of core components and key targets.

Results: UPLC-Q-TOF-MS/MS detected 482 components of BXD, Among the main components of BXD are flavonoids, triterpenoid saponins, alkaloids, glycosides, etc., and comprehensive analysis and screening yielded 165 active ingredients, including quercetin, kaempferol, baicalein, naringenin, etc. There were 283 targets related to BXD's treatment of CC, of which the core targets included AKT1, IL-6, TP53, ALB, etc. GO enrichment analysis yielded relevant entries including molecular function 60 entries, 257 entries of biological processes, and 31 entries of cellular composition, and KEGG enrichment analysis identified 150 entries involving IL-17, TNF, PI3K-Akt, and other pathways. The molecular docking results demonstrated that the core components exhibited better binding activities with the key targets.

Conclusion: Quercetin, kaempferol, baicalein, and naringenin, the main active ingredients in BXD, may play roles in anti-inflammatory, antimicrobial, and regulating intestinal microbiota to achieve the therapeutic purpose of CC treatment by mediating the targets of AKT1, IL-6, TP53, and ALB, and regulating the signaling pathways of IL-17, TNF, and PI3K-Akt.