Sophora japonica Extract Inhibits Ulcerative Colitis and Colitis-Associated Colon Cancer via Regulation of Lipid Metabolism

Abstract

Inflammation is a well-known risk factor for tumor development. Intervening in chronic inflammation may be an effective approach to inhibit the progression of ulcerative colitis (UC) to colitis-associated colon cancer (CAC). Sophora japonica is a medicinal and food plant commonly used to treat hemorrhoids, bleeding, and inflammation, symptoms that coincide with those of patients with CAC. However, studies on using Sophora japonica to treat CAC are scarce. Therefore, this study aimed to investigate the anti-inflammatory and antitumor effects of Sophora japonica extract (SJE) using dextran sodium sulfate (DSS)-induced UC and azoxymethane (AOM)/DSS-induced CAC models. Furthermore, we employed ultraperformance liquid chromatography–quadrupole time-of-flight–tandem mass spectrometry (UPLC–QTOF–MS/MS) technology to explore the metabolomics mechanism through which SJE inhibited the progression of UC to CAC. The results demonstrated that SJE significantly inhibited UC and CAC and alleviated symptoms such as bloody stools, colon shortening, inflammation, and intestinal tissue damage in model mice. Further, 57 differential metabolites were identified by UPLC–QTOF–MS/MS, which were composed mainly of lipids (fatty acids, glycerophospholipids, sterol lipids, pregnenolone lipids, etc.) and peptides (amino acids). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that SJE might inhibit the progression of UC to CAC by regulating lipid metabolic pathways such as arachidonic acid metabolism, primary bile acid biosynthesis, and linoleic acid metabolism. This study, for the first time, substantiated the inhibitory effect of SJE on CAC. Employing metabolomics techniques, the research delved into the potential pathways through which SJE may exert its inhibitory effects on CAC by suppressing the progression of UC. These findings contribute scientific evidence to the application of Sophora japonica in functional foods and the development of natural drugs for the prevention and treatment of UC and CAC.