基于入血成分分析莲胆消炎方抗溃疡性结肠炎的作用机制

Mechanism Study of Liandan Xiaoyan Prescription on Attenuating Ulcerative Colitis Based on the Components into the Blood Analysis

目的:基于入血成分分析莲胆消炎方(LDXYF)治疗溃疡性结肠炎(UC)的作用机制。方法:使用高分辨飞行时间质谱解析LDXYF的入血成分;检索TCMSP和SwissTargetPrediction等数据库获取入血成分的作用靶点;利用Gene Cards和OMIM数据库得到UC疾病相关靶点;借助Cytoscape 3.7.2软件构建“成分-靶点-通路”网络,结合蛋白质相互作用分析平台(String)进行GO、KEGG通路富集分析;使用Autodock 3.2.4软件将入血成分与关键靶点进行分子对接。结果:实验鉴定出15个LDXYF的入血成分,获得53个潜在作用靶点,IL6、TNF、TLR4、AKT1和STAT3等是LDXYF治疗UC的主要作用靶点,涉及TNF信号通路、Th17细胞分化和Toll样受体信号等通路。分子对接结果表明Andrographolide、Dehydroandrographolide、4-Methoxy-5-hydroxy-canthin-6-one和1-Methoxycarbonyl-β-carboline对TLR4、AKT1、STAT3或IKKB均具有较好的结合活性。结论:LDXYF的入血成分主要为生物碱和二萜内酯,这些成分可能作用于TNF信号通路、Th17细胞分化和Toll样受体信号通路相关的靶点,进而影响UC疾病发展。

Objective:To elucidate the mechanism of Liandan xiaoyan prescription(LDXYF)on attenuating ulcerative colitis(UC)based on the components into the blood.Methods:UPLC-Q-TOF-MS/MS was used to identify the main chemical constituents of LDXYF into the blood.The targets of the compounds of LDXYF into the blood were screened in TCMSP and SwissTargetPrediction databases.The disease targets of UC were obtained by Gene Cards and OMIM databases.The network of″components-targets-pathways″was constructed by Cytoscape 3.7.2 software.The protein interaction analysis platform(STRING)was used to GO and KEGG pathways enrichment analysis.Autdoock 3.2.4 software was used to conduct molecular docking between components into the blood and key targets.Results:Fifteen components of LDXYF into the blood were identified,53 potential targets related to UC were obtained.IL6,TNF,TLR4,AKT1,STAT3 and others were the key targets of LDXYF in the treatment of UC,which involved TNF signaling pathway,Th17 cell differentiation and Toll-like receptor signaling pathway.The results of molecular docking showed that andrographolide,dehydroandrographolide,4-methoxy-5-hydroxy-canthin-6-one and 1-methoxycarbonyl-β-carboline could bind to the targets of TLR4,AKT1,STAT3 or IKKB.Conclusion:The main components of LDXYF into the blood include alkaloids and diterpenoids.These components may act on targets related to the TNF signaling pathway,Th17 cell differentiation and Toll-like receptor signaling pathway,and thus affect the disease development of UC.