基于网络药理学和动物实验探究黄芩茎叶总黄酮对溃疡性结肠炎的治疗作用及机制

Study on Effect and Mechanism of Total Flavonoids from Stem and Leaf of Scutellaria Baicalensis on Ulcerative Colitis Based on Network Pharmacology and Animal Experiments

关键词:  网络药理学  黄芩茎叶总黄酮  溃疡性结肠炎  AhR/IL-22依赖信号通路

Key words:  network pharmacology  total flavonoids from stem and leaf of Scutellaria baicalensis  ulcerative colitis  AhR/IL-22 depends on the signaling pathway

摘要:

目的 基于网络药理学和动物实验探究黄芩茎叶总黄酮治疗溃疡性结肠炎的作用机制。方法 通过文献查阅黄芩茎叶中总黄酮成分，并根据中药系统药理学数据库与分析平台(TCMSP)检索黄芩茎叶总黄酮成分对应靶点，通过GeneCards数据库收集溃疡性结肠炎相关靶点。使用Venny 2.1绘图软件获取药物和疾病相关靶点的交集靶点，将其上传至STRING数据平台进行蛋白质-蛋白质相互作用网络构建，再采用DAVID数据平台进行基因本体(gene ontology，GO)功能和京都基因与基因组百科全书(Kyoto encyclo pedia of genes and genomes，KEGG)通路富集分析。采用3% DSS诱导的溃疡性结肠炎小鼠模型对网络药理学结果进行验证。结果 网络药理学结果表明，黄芩茎叶总黄酮7个成分对应69个相关靶点，溃疡性结肠炎相关靶点1383个，交集靶点24个。GO和KEGG通路富集分析获得黄芩茎叶总黄酮治疗溃疡性的潜在通路，包括芳香烃受体(aryl hydrocarbon receptor，AhR)、Th17细胞分化、T细胞受体等。3% DSS诱导的溃疡性结肠炎小鼠模型结果显示，与模型组相比，黄芩茎叶总黄酮显著降低MPO、TNF-α、IL-1β、IL-17水平，增加IL-10和IL-22水平，且具有统计学差异，恢复小鼠结肠长度。激活AhR通路及其中CYP1A1和CYP1B1靶点，从而促进抗炎因子IL-22因子的水平，通过激活ZO-1蛋白表达修复肠道屏障。结论 黄芩茎叶总黄酮能够基于多成分、多靶点、多通路的特点相互协同治疗溃疡性结肠炎。

Abstract:

OBJECTIVE To explore the mechanism of total flavonoids from stem and leaf of Scutellaria baicalensis in treating ulcerative colitis based on network pharmacology and animal experiments. METHODS The total flavonoids in stem and leaves of Scutellaria baicalensis were reviewed in literature, the corres ponding targets of total flavonoids in stem and leaves of Scutellaria baicalensis were retrieved by TCM systematic pharmacology database and analysis platform(TCMSP), and the related targets of ulcerative colitis were collected by GeneCards database. The corres ponding targets of total flavonoids from the stem and leaves of Scutellaria baicalensis and those related to ulcerative colitis were in put into Venny 2.1 mapping software to obtain the intersection targets, which were uploaded to STRING data platform for the construction of protein-protein interaction network. The gene ontology(GO) functions and the Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment were analyzed using the DAVID data platform jointly. The network pharmacological results were verified in a mouse model of ulcerative colitis induced by 3% DSS. RESULTS The results of network pharmacology showed that there were 69 related targets, 1383 related targets in ulcerative colitis and 24 overlapping targets in 7 components of total flavonoids from stem and leaves of Scutellaria baicalae. GO and KEGG pathway enrichment analysis were conducted to obtain the potential pathways of total flavonoids from stem and leaves of Scutellaria baicalensis in the treatment of ulcerative effects, including aryl hydrocarbon receptor(AhR), Th17 cell differentiation, T cell receptor, etc. The results of 3% DSS induced ulcerative colitis mouse model showed that compared with the model group, total flavonoids of scutellaria scutellaria stem and leaf significantly decreased the levels of MPO, TNF-α, IL-1β and IL-17 and increased levels of IL-10 and IL-22 with statistical difference, and restored the colon length of mice. Activated the AhR pathway and its CYP1A1 and CYP1B1 targets to promote the expression of anti-inflammatory factor IL-22, and repair the intestinal barrier by activating ZO-1 proteins. CONCLUSION Total flavonoids from stem and leaf of Scutellaria scutellaria can synergistically treat ulcerative colitis based on the characteristics of multi-component, multi-target and multi-pathway.