背景:苦参常用于治疗皮肤问题的中药,腹泻,和阴道瘙痒(植物名称已通过http://www进行了检查。2月22日的plantlist.org,2024).氧化苦参碱(OY),苦参是一种主要的生物活性化合物,在中国通常用于治疗溃疡性结肠炎,但其机制仍不清楚。
目的:最近的研究发现,铁细胞凋亡与炎症的相互作用是UC发病的重要机制。这项研究的目的是探讨OY治疗DSS诱导的溃疡性结肠炎的潜在潜在机制。特别关注铁死亡和炎症的过程。
方法:生物信息学方法用于确定OY在溃疡性结肠炎中铁凋亡和炎症的关键靶标,基于GEO数据和FerrDb数据库。然后,4%DSS溶液诱导UC模型。使用结肠视图评估OY对形态变化的影响,苏木精和伊红(HE)染色,和透射电子显微镜(TEM)。采用酶联免疫吸附试验(ELISA)或化学生物检测试剂盒检测铁凋亡表型指标和炎症因子,采用RT-PCR方法筛选铁凋亡和炎症相关基因。免疫组织化学(IHC),免疫荧光(IF),和蛋白质印迹(WB)。
结果:生物信息学结果表明,有16个关键靶基因参与OY治疗UC的铁凋亡和炎症相互作用,例如IL6、NOS2、IDO1、SOCS1和DUOX。动物实验结果表明OY能抑制炎症因子(IL-1β,IL-6,TNF-α,HMGB1和NLRP3)和减少铁沉积(Fe2+,GSH,和铁蛋白)。此外,OY抑制了与铁死亡和炎症有关的hub基因或蛋白质表达,包括IL-1β,IL-6,NOS2,HIF1A,IDO1、TIMP1和DUOX2。
结论:本研究结合了生物信息学,分子生物学,动物实验研究表明,OY通过改善铁蛋白和炎症反应来减轻UC,主要针对IL-1β的表达,IL-6,NOS2,HIF1A,IDO1、TIMP1和DUOX2。
BACKGROUND: 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.
OBJECTIVE: 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.
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-1β, IL-6, TNF-α, 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-1β, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2.
CONCLUSIONS: 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-1β, IL-6, NOS2, HIF1A, IDO1, TIMP1, and DUOX2.