黄芩汤配伍使用白芍、赤芍抗溃疡性结肠炎作用比较

Comparison of Anti-ulcerative Colitis Effect of Huangqin Decoction Combined with Paeoniae Radix Alba and Paeoniae Radix Rubra

关键词:  黄芩汤  白芍  赤芍  网络药理学  溃疡性结肠炎  Notch信号通路

Key words:  Huangqin decoction  Paeoniae Radix Alba  Paeoniae Radix Rubra  network pharmacology  ulcerative colitis  Notch signaling pathway

摘要:

目的 基于网络药理学分析和动物实验比较黄芩汤配伍使用白芍、赤芍抗溃疡性结肠炎(ulcerative colitis，UC)的作用差异。方法 从TCMSP数据库和文献中检索白芍与赤芍活性成分，通过Swiss Target Prediction预测潜在靶点；以Ulcerative Colitis为关键词在DisGenet、OMIM、Genecard数据库检索疾病靶点；利用Venny 2.1.0获取交集靶点，Cytoscape 3.7.2软件构建“药物-成分”靶点网络，STRING平台进行蛋白质互作(protein-protein interaction，PPI)网络分析，Metascape数据库进行GO/WIKI分析。采用葡聚糖硫酸钠(dextran sulfate sodium，DSS)诱导建立UC小鼠模型，观察分别黄芩汤配伍使用白芍(HQT-BS)和赤芍(HQT-CS)对UC的防治作用，并比较异同。结果 HQT-BS、HQT-CS治疗UC的活性成分别有7，11个，其中共有成分5个；靶点分别有146，157个，其中共有靶点106个，HQT-BS核心靶点为SRC、HSP90AA1、PIK3R1，HQT-CS核心靶点为SRC、HSP90AA1、STAT3。WIKI富集分析显示，白芍与赤芍共有信号通路包含EGFR tyrosine kinase inhibitor resistance、Notch signaling pathway等，EGF/EGFR signaling pathway及Nuclear receptors meta-pathway、Kit receptor signaling pathway分别为白芍和赤芍所特有的炎症相关信号通路。动物实验研究表明，HQT-BS、HQT-CS的黄芩汤均能显著改善模型小鼠结肠缩短及组织病理学改变，但在降低炎症因子白细胞介素-6及神经源性基因座缺口同源蛋白1表达方面，HQT-CS的黄芩汤效果较明显。结论 HQT-BS、HQT-CS的黄芩汤均具有抗UC作用，黄芩汤配伍使用赤芍抗炎作用较优。

Abstract:

OBJECTIVE To study the difference of Huangqin decoction combined with Paeoniae Radix Alba(BS) and Paeoniae Radix Rubra(CS)'s effect on ulcerative colitis(UC) based on network pharmacological analysis and animal experiment. METHODS The active constituents of BS and CS were retrieved from TCMSP database and literature, and the potential target was predicted by Swiss Target Prediction. Ulcerative Colitis was used as key words to search disease targets in DisGenet, OMIM, and Genecard databases. The intersection target was obtained by Venny 2.1.0. Cytoscape 3.7.2 software was used to construct network of drug-consumption targets. The STRING platform was used for protein-protein interaction(PPI) network analysis, and Metascape database was applied for GO/WIKI analysis. A dextran sulfate sodium(DSS) induced UC mouse model was established to compare the anti-UC effects of Huangqing decoction combined with BS(HQT-BS) and CS(HQT-CS), respectively. RESULTS There were 7 active components of HQT-BS and 11 active components of HQT-CS in the treatment of ulcerative colitis, respectively, 5 of which were the same. There were 146 and 157 targets respectively, 106 of which were the same. The core targets of HQT-BS were SRC, HSP90AA1, and PIK3R1, while the core targets of HQT-CS were SRC, HSP90AA1, and STAT3. WIKI enrichment analysis showed that several signaling pathways were shared by both BS and CS, such as EGFR tyrosine kinase inhibitor resistance, Notch signaling pathway. EGF/EGFR signaling pathway was the specific pathway related to BS, while Nuclear receptors meta-pathway and Kit receptor signaling pathway were the specific pathways related to CS, respectively. Animal experiments showed that both HQT-BS and HQT-CS could significantly improve colon shortening and tissue pathological alternation induced by DSS. However, HQT-CS was more effective in reducing the expression of interleukin-6 and neurogenic locus notch homolog protein1. CONCLUSION Both HQT-BS and HQT-CS have anti-UC effect, and HQT-CS is the better one.