基于网络药理学探究蒲参胶囊治疗高脂血症的作用机制
Study on Mechanism of Pushen Capsule for Treating Hyperlipidemia Based on Network Pharmacology
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摘要: 目的 基于网络药理学方法,构建蒲参胶囊药效物质靶点网络,分析其功效物质基础和作用靶标,阐述其治疗高脂血症的可能分子机制,为蒲参胶囊抗高脂血症的实验研究提供思路。方法 首先基于Arrowsmith非文献预测工具探讨蒲参胶囊各味中药及其组分和高脂血症的相关性。其次运用中药成分数据库联合Percepta平台ADME/T预测功能筛选蒲参胶囊药效活性成分,于Similarity Ensemble Approach,STITCH和Benchmark Database分子靶点网站确定活性成分作用靶点。接着使用GeneCards搜索高脂血症相关疾病靶点,联合活性化合物作用靶点,确定药物作用与高脂血症的共同潜在靶标,并使用Cytoscape将结果可视化展示,最后通过使用KEGG数据库及DAVID数据库进行靶标注释与分类。结果 通过Arrowsmith分析得出,蒲参胶囊各味中药药物作用靶点和高脂血症以及其相关疾病如“动脉粥样硬化”“糖尿病”等具有显著相关性,提示蒲参胶囊对这些疾病具有治疗作用。通过药理学方法筛选出活性成分共75个,主要作用靶标有261个,关键靶点和炎症反应相关。基于KEGG和DAVID数据库总结蒲参胶囊发挥活血化瘀,滋阴化浊的治疗作用主要可能是通过以下几条信号通路:①AGE-RAGE信号通路;②Malaria相关途径;③乙型肝炎相关途径;④VEGF信号通路;⑤肿瘤相关途径。结论 蒲参胶囊治疗高脂血症是通过多靶点、多通路共同作用,主要作用环节集中在抑制慢性炎症的发生发展。Abstract: OBJECTIVE Based on the network pharmacology technology, this research explores the medicinal substance basis and target of the Pushen capsule, and constructs a network of medicinal potential targets to explain the possible mechanism of the Pushen capsule in the treatment of hyperlipidemia, and provide research ideas for the pharmacodynamic basis of the Pushen capsule. METHODS Firstly, based on the Arrowsmith non-document prediction tool, the correlation between the Pushen capsule and its components and hyperlipidemia was discussed. Using the Chinese medicine ingredient database combined with the Percepta platform ADME/T predictive function to screen the active ingredients of the Pushen capsule, and determining the active ingredient target with the Similarity Ensemble Approach, STITCH and Benchmark Database molecular target sites. Applying GeneCards to search for hyperlipidemia-related disease targets, then combining active compound targets and identifying potential targets for drugs and hyperlipidemia, finally visualizing the results with cytoscape. Target annotation and classification can be made by using of the KEGG database and the DAVID database. RESULTS Through analyzing date of Arrowsmith, there was a significant correlation between the Pushen capsule and hyperlipidemia, as well as related diseases such as "atherosclerosis" and "diabetes", suggest that Pushen capsule has therapeutic effects on these diseases. A total of 75 active ingredients were screened by pharmacological methods, and the main target was 261 and Critical targets associated with inflammatory responses. Based on the KEGG and DAVID databases, the effect of Pushen capsule on improving blood circulation and removing phlegm was mainly through the following signal pathways: ①AGE-RAGE signaling pathway,②Malaria related pathway,③hepatitis B related pathway,④VEGF signaling pathway,⑤Cancer related pathway. CONCLUSION The treatment of hyperlipidemia with Pushen Capsule is through multiple targets and multiple pathways. The main effort is focused on reducing chronic inflammation.