Ren Beida, Tan Ling, Xiong Yiliang, Ji Wenting, Mu Jie, Pei Yuying, Cheng Fafeng, Wang Xueqian, Wang Qingguo
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
Evid Based Complement Alternat Med. 2020 Apr 28;2020:9768414. doi: 10.1155/2020/9768414. eCollection 2020.
The incidence of type 2 diabetes mellitus (T2DM) has increased year by year, which not only seriously affects people's quality of life, but also imposes a heavy economic burden on the family, society, and country. Currently, the pathogenesis, diagnosis, and treatment of T2DM are still unclear. Therefore, exploration of a precise multitarget treatment strategy is urgent. Here, we attempt to screen out the active components, effective targets, and functional pathways of therapeutic drugs through network pharmacology with taking advantages of traditional Chinese medicine (TCM) formulas for multitarget holistic treatment of diseases to clarify the potential therapeutic mechanism of TCM formulas and provide a systematic and clear thought for T2DM treatment.
First, we screened the active components of Da-Chai-Hu Decoction (DCHD) by absorption, distribution, metabolism, excretion, and toxicity (ADME/T) calculation. Second, we predicted and screened the active components of DCHD and its therapeutic targets for T2DM relying on the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP database) and Text Mining Tool (GoPubMed database), while using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to obtain T2DM targets. Third, we constructed a network of the active component-target, target-pathway of DCHD using Cytoscape software (http://cytoscape.org/,ver.3.5.1) and then analyzed gene function, related biological processes, and signal pathways through the DAVID database.
We screened 77 active components from 1278 DCHD components and 116 effective targets from 253 ones. After matching the targets of T2DM, we obtained 38 important targets and 7 core targets were selected through further analysis. Through enrichment analysis, we found that these important targets were mainly involved in many biological processes such as oxidative stress, inflammatory reaction, and apoptosis. After analyzing the relevant pathways, the synthetic pathway for the treatment of T2DM was obtained, which provided a diagnosis-treatment idea for DCHD in the treatment of T2DM.
This article reveals the mechanism of DCHD in the treatment of T2DM related to inflammatory response and apoptosis through network pharmacology, which lays a foundation for further elucidation of drugs effective targets.
2型糖尿病（T2DM）的发病率逐年上升，不仅严重影响人们的生活质量，也给家庭、社会和国家带来沉重的经济负担。目前，T2DM的发病机制、诊断和治疗仍不明确。因此，探索精确的多靶点治疗策略迫在眉睫。在此，我们试图通过网络药理学，利用中药方剂对疾病进行多靶点整体治疗的优势，筛选出治疗药物的活性成分、有效靶点和功能通路，以阐明中药方剂的潜在治疗机制，为T2DM的治疗提供系统清晰的思路。
首先，通过吸收、分布、代谢、排泄和毒性（ADME/T）计算筛选大柴胡汤（DCHD）的活性成分。其次，依托中药系统药理学分析平台（TCMSP数据库）和文本挖掘工具（GoPubMed数据库）预测和筛选DCHD及其治疗T2DM的靶点，同时利用注释、可视化和综合发现数据库（DAVID）获取T2DM靶点。第三，使用Cytoscape软件（http://cytoscape.org/，版本3.5.1）构建DCHD的活性成分-靶点、靶点-通路网络，然后通过DAVID数据库分析基因功能、相关生物学过程和信号通路。
我们从1278种DCHD成分中筛选出77种活性成分，从253种成分中筛选出116个有效靶点。在匹配T2DM的靶点后，我们获得了38个重要靶点，并通过进一步分析选出7个核心靶点。通过富集分析，我们发现这些重要靶点主要参与氧化应激、炎症反应和细胞凋亡等多种生物学过程。在分析相关通路后，获得了治疗T2DM的合成通路，为DCHD治疗T2DM提供了诊疗思路。
本文通过网络药理学揭示了DCHD治疗T2DM与炎症反应和细胞凋亡相关的机制，为进一步阐明药物有效靶点奠定了基础。
