Beneficial effects of oxymatrine from Sophora flavescens on alleviating <bold>Ulcerative colitis</bold> by improving inflammation and ferroptosis

Ethnopharmacological relevance: Sophora flavescens is often used in traditional Chinese medicine for skin issues, diarrhea, and vaginal itching (Plant names have been checked with http://www.the/plant/list.org on Feb 22nd, 2024). Oxymatrine (OY), a major bioactive compound from Sophora flavescens, is commonly used in China to treat ulcerative colitis, but its mechanisms are still unclear. Aim of the study: Recent studies have found that the crosstalk between ferroptosis and inflammation is an important mechanism in the pathogenesis of UC. The aim of this study was to investigate the potential underlying mechanisms of OY treatment on DSS-induced ulcerative colitis, specifically focusing on the processes of ferroptosis and inflammation. Materials and methods: Bioinformatics methods were used to identify key targets of OY for ferroptosis and inflammation in ulcerative colitis, based on GEO data and FerrDb database. Then, 4% DSS solution was used to induce UC model. OY's impact on morphological changes was assessed using colon views, Hematoxylin and eosin (HE) staining, and transmission electron microscopy (TEM). Ferroptosis phenotype index and inflammations factors were detected by ELISA or chem-bio detection kits. The screen out hub related genes about ferroptosis and inflammation were verified by RT-PCR, immunohistochemistry (IHC), and western blotting (WB) respectively. Results: Bioinformatics results show that there are 16 key target genes involved in ferroptosis and inflammation interaction of OY treatment for UC, such as IL6, NOS2, IDO1, SOCS1, and DUOX. The results of animal experiments show that OY could depress inflammatory factors (IL-1 beta, IL-6, TNF-alpha, HMGB1, and NLRP3) and reduce iron deposition (Fe2+, GSH). Additionally, OY suppressed the hub genes or proteins expression involved in ferroptosis and inflammation, including IL-1 beta, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2. Conclusion: This present study combines bioinformatics, molecular biology, and animal experimental research evidently demonstrated that OY attenuates UC by improving ferroptosis and inflammation, mainly target to the expression of IL-1 beta, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2.