基于生物信息学与分子对接技术探讨苦参通过调节免疫相关基因治疗溃疡性结肠炎的分子机制

Molecular Mechanism of Sophora Flavescens in the Treatment of Ulcerative Colitis Through Regulating Immune-Related Gene Based on Bioinformatics and Molecular Docking

目的:基于生物信息学和分子对接技术,探讨苦参治疗溃疡性结肠炎(UC)的药理作用机制。方法:通过中药系统药理学数据库与分析平台及相关文献获取苦参的成分靶点信息,应用GEO数据库中的数据集(GSE206285)获取UC差异表达基因,通过免疫相关基因(IRGs)数据库收集IRGs,再利用STRING平台进行蛋白质-蛋白质相互作用分析,筛选苦参通过调节IRGs的表达治疗UC的核心靶点。通过Metascape平台对相关基因进行富集分析,最后将苦参中主要活性成分与核心靶点进行分子对接验证。结果:苦参通过调节免疫相关蛋白治疗UC的潜在活性成分为槲皮素、木犀草素、刺芒柄花素、8-异戊烯基-山柰酚、菜豆素、怀特酮、大豆抗毒素、高丽槐素、苦参素和苦参碱;核心靶点为基质金属蛋白酶(MMP)9、白细胞介素(IL)1β、CXC趋化因子配体8(CXCL8)、过氧化物酶体增生激活受体γ(PPARG)、前列腺素内过氧化物合成酶2(PTGS2)和IL-6;参与的信号通路为癌症相关通路、脂质与动脉粥样硬化通路、AGE-RAGE信号通路、IL-17信号通路以及肿瘤坏死因子信号通路等;MMP9与怀特酮的结合能为-42.7 kJ/mol;PPARG与菜豆素的结合能为-41.9 kJ/mol;MMP9与木犀草素、PTGS2与木犀草素、PTGS2与菜豆素、PTGS2与大豆抗毒素的结合能均为-40.6 kJ/mol。结论:本研究探讨了苦参通过调节IRGs治疗UC的潜在机制,为苦参临床应用的拓展及UC新的治疗策略提供理论基础。

OBJECTIVE:To analyze the pharmacological mechanism of sophora flavescens in the treatment of ulcerative colitis(UC)based on bioinformatics and molecular docking.METHODS:The ingredients target information of sophora flavescens was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and related literature,the differential expression genes of UC were obtained by using the dataset(GSE206285)in the GEO database,the IRGs were collected through immune-related gene(IRGs)database,and STRING platform was used to perform protein-protein interaction analysis,so as to screen the core targets of sophora flavescens in the treatment of UC through regulating the expression of IRGs.The enrichment analysis on related gene was conducted by using Metascape platform,and molecular docking verification was finally conducted on the main active ingredients and core targets in sophora flavescens.RESULTS:The potential active ingredients of sophora flavescens in the treatment of UC by regulating immune-related proteins were quercetin,luteolin,formononetin,8-isoprenyl-kaempferol,phaseolin,wighteone,glyceollin,maackiain,kushenin and matrine;the core targets were matrix metalloproteinase(MMP)9,interleukin(IL)1β,CXC chemokine ligand 8(CXCL8),PPARG,PTGS2 and IL-6;the involved signaling pathways were cancer-related pathway,lipid and atherosclerosis pathway,AGE-RAGE signaling pathway,IL-17 signaling pathway and tumor necrosis factor signaling pathway,etc.;the binding energy of MMP9 to wighteone was-42.7 kJ/mol;the binding energy of PPARG to phaseolin was-41.9 kJ/mol;the binding energy of MMP9 to luteolin,PTGS2 to luteolin,PTGS2 to phaseolin and PTGS2 to glyceollin were-40.6 kJ/mol.CONCLUSIONS:This study has explored the potential mechanism of sophora flavescens in the treatment of UC by regulating IRGs,so as to provided a theoretical basis for the expansion of the clinical application of sophora flavescens and new therapeutic strategies for UC.