首页|白术治疗溃疡性结肠炎作用机制的网络药理学分析及实验验证研究

白术治疗溃疡性结肠炎作用机制的网络药理学分析及实验验证研究

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目的 基于网络药理学探究并预测白术治疗溃疡性结肠炎(UC)的作用靶点及分子机制,并加以动物实验验证。方法 从TCMSP数据库、TCM-ID数据库以及结合相关参考文献筛选出白术的活性成分,在Swiss数据库获得对应靶点,从GeneCards数据库中获取UC疾病的相关靶点,分别构建"药物-成分-靶点-疾病"网络图、"通路-活性成分-靶点"网络图以及绘制PPI核心靶点网络图,并进行GO功能富集分析和KEGG通路注释分析,然后进行活性成分与核心靶点的分子对接。以葡聚糖硫酸钠(DSS)诱导小鼠UC模型,通过采用苏木精-伊红染色法(Hematoxylin-Eosin staining)、AB-PAS染色法及免疫组织化学法分别检测小鼠结肠组织中病理形态学变化、杯状细胞数目以及炎症因子的表达情况,进行网络药理学预测结果的实验验证。结果 筛选出白术内酯I、II、III等30个活性成分,获取其活性成分对应靶点591个,其中关键靶点有IL-1β、TNF-α等,分子对接结果显示IL-1β、TNF-α与核心成分具有良好的结合能力。动物实验结果显示,白术醇提物组可明显增加UC小鼠的结肠长度、降低DAI评分,还可改善UC小鼠结肠组织病变情况,增加杯状细胞的个数,抑制结肠组织中IL-1β、TNF-α的高表达。结论 该研究表明白术可通过多组分、多靶点、多通路调控炎症因子的释放而抑制炎症反应,发挥改善UC的药效作用。
Mechanism of Atractylodes macrocephala in Treatment of Ulcerative Colitis Based on Network Pharmacology and Experimental Validation
Objective To explore the molecular mechanism of Atractylodes macrocephala in the treatment of Ulcerative colitis(UC)based on network pharmacology,and verify it with animal experiments.Methods The active components of Atractylodes macrocephala was screened from the TCMSP database,the TCM-ID database,and in combination with relevant references,and the corresponding targets were obtained through Swiss database.The relevant targets of UC were obtained from GeneCards database,construct the"drug-component-target-disease"network diagram and"pathway-active ingredient-target"network diagram and draw PPI network diagram;GO function enrichment analysis and KEGG signal pathway annotation analysis were carried out.Autodock software is used for molecular docking of active components and targets.Then,the experimental validation of the network pharmacology prediction was carried out.The mouse UC model was induced by dextran sodium sulfate(DSS).The pathological changes of the colon tissue,the number of goblet cells,and the positive expression of inflammatory factorswere detected by HE staining,AB-PAS staining and immunohistochemistry in colon tissue of UC mice.Results The results have shown 30 active ingredients including atractylolactone I,II and III were screened,and 591 corresponding targets were obtained,of which the key target was IL-1β、TNF-α and so on.Molecular docking show that the core components had good binding affinity with the key targets.And the results of animal experiments showed that the alcohol extract of Atractylodes macrocephala could significantly increase the colon length,reduce the DAI score,improve the pathological changes of colon tissue of UC mice,increase the number of goblet cells,and inhibit the expression of IL-1β,TNF-α in colon tissue.Conclusion This study indicated that Atractylodes macrocephala could regulate the release of inflammatory factors through multiple components,multi-target and multi-channel,which could inhibit inflammatory reaction and play a role in improving UC.

Atractylodes macrocephalaNetwork pharmacologyMolecular dockingUlcerative colitisInflammatory response

余学成、高增祥、吴斌、涂济源、陈林霖、曹国胜

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湖北中医药大学药学院 武汉 430065

湖北省中药炮制工程技术研究中心 武汉 430065

白术 网络药理学 分子对接 溃疡性结肠炎 炎症反应

湖北省科技厅自然科学研究面上项目

2022CFB375

2024

世界科学技术-中医药现代化
中科院科技政策与管理科学研究所,中国高技术产业发展促进会

世界科学技术-中医药现代化

CSTPCD北大核心
影响因子:1.175
ISSN:1674-3849
年,卷(期):2024.26(1)
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