大血藤对溃疡性结肠炎的治疗作用及基于GEO芯片联合网络药理学的机制探讨

Therapeutic Effect of Sargentodoxae Caulis on Ulcerative Colitis and Exploring the Mechanism Based on GEO Chip Combined with Network Pharmacology

关键词:  大血藤  溃疡性结肠炎  GEO芯片  网络药理学  分子对接  作用机制

Key words:  Sargentodoxae Caulis  ulcerative colitis  GEO chip  network pharmacology  molecular docking  mechanism

摘要:

目的 明确大血藤抗溃疡性结肠炎(ulcerative colitis，UC)的作用，并探讨其作用机制。方法 以葡聚糖硫酸钠诱导UC小鼠模型评价大血藤抗UC作用；依据中国知网和PubMed网站获取大血藤的成分，SwissTargetPrediction数据库筛选成分靶点，GEO基因芯片提取UC差异基因，构建大血藤“成分-靶点-疾病”网络，筛选核心靶点后，进行蛋白互作与聚类分析、生物过程及通路富集分析，并以分子对接和文献初步验证网络分析的可靠性。结果 大血藤能显著改善UC小鼠的疾病活动指数评分、结肠缩短和结肠组织病理变化，具有良好的抗UC作用；网络分析发现大血藤抗UC核心成分包括(+)-Dihydroguaiaretic acid、Isorhapontigenin和Pinosylvin等，核心靶点EGFR、STAT1、LCK等63个，通过调节PI3K-Akt信号通路和癌症蛋白聚糖等多条免疫抗炎和抗肿瘤相关的信号通路，影响氨基酸修饰，激酶活性调节，细胞反应和氧化应激等生物过程抗UC。分子对接和文献表明所构建网络可靠性较高。结论 大血藤有良好的抗UC作用，其机制可能与调节肠道免疫炎症及细胞增殖、分化与迁移等密切相关，具备多成分、多靶点、多途径的特点。

Abstract:

OBJECTIVE To study the anti-ulcerative colitis(UC) effect of Sargentodoxae Caulis and explore its mechanism. METHODS The UC mice model induced by dextran sodium sulfate was used to evaluate the anti-UC effect of Sargentodoxae Caulis. The ingredients of Sargentodoxae Caulis were obtained according to the CNKI and PubMed website, component targets were screened by SwissTargetPrediction database, GEO gene chip was used to extract UC differential genes, then a network of "ingredients-targets-disease" of the Sargentodoxae Caulis was constructed. After screening the core targets, protein interaction and cluster analysis, biological process and pathway enrichment analysis were performed, and the reliability of network analysis was preliminarily verified by molecular docking and literatures. RESULTS Sargentodoxae Caulis could significantly improve the disease activity index score, colon shortening and colonic histopathological changes of UC mice, and had a good anti-UC effect. The network analysis found that the core components of the anti-UC of Sargentodoxae Caulis include (+)-Dihydroxyurearetic acid, Isorhaponigenin and Pinosylvin, and 63 core targets, such as EGFR, STAT1 and LCK, regulating PI3K-Akt signal pathway and cancer proteoglycan and other related signal pathways of immune anti-inflammatory and anti-cancer, and it could affect the biological processes such as amino acid modification, kinase activity regulation, cell reaction and oxidative stress to treat UC. Molecular docking and literature showed that the constructed network had high reliability. CONCLUSION Sargentodoxae Caulis has a good anti-UC effect, and its mechanism may be closely related to the regulation of intestinal immune inflammation and cell proliferation, differentiation and migration. It has the characteristics of multi-component, multi-target and multi-way.