Ba-Jia Gong, Yue Ren, Jing M A, Sang Geng, Jie-Ren-Qing Duo, Gong-Yu L I, Ma-Ci-Ren N I, Yan-Ling Zhang
Beijing University of Chinese Medicine Beijing 102488, China Tha Xi Ke Community Health Service Center in Yushu Yushu 815000, China.
Beijing University of Chinese Medicine Beijing 102488, China.
Zhongguo Zhong Yao Za Zhi. 2020 Nov;45(22):5383-5392. doi: 10.19540/j.cnki.cjcmm.20200707.401.
Hypertension is a kind of chronic cardiovascular system disease caused by a series of factors and carriers dysfunction, which belongs to the category of Tibetan medicine "Chalong disease", and has a high rate of disability and mortality. Zuomua Decoction is a classical Tibetan medicine for Chalong disease, but its mechanism is not clear. Therefore, in this paper we explored the multi-components, multi-targets and multi-channels mechanism of Zuomua Decoction in the treatment of hypertension based on network pharmacology and molecular docking technology. First of all, the chemical components of Zuomua Decoction were obtained in the retrieval of traditional Chinese medicine systems pharmacology database(TCMSP), China National Knowledge Infrastructure(CNKI) and Wanfang database. The potential targets of Zuomua Decoction were predicted by BATMAN-TCM database, and the targets of hypertension were obtained by using DisGeNET database. The intersection of these two targets set was taken to obtain the potential targets of Zuomua Decoction in the treatment of hypertension, and then the chemical compositions-targets network was constructed. Secondly, the intersection targets were imported into STRING database to obtain the interaction relationship of intersection targets, and the protein interaction network of Zuomua Decoction in the treatment of hypertension was constructed in Cytoscape. Topological, GO, and KEGG enrichment analysis were used to construct the key targets-signal pathways-biological processes network diagram and explore the mechanism of Zuomua Decoction in the treatment of hypertension. Finally, the key targets were selected to construct the pharmacodynamic identification models to verify the effect mode of Zomua Decoction in treating hypertension. The results showed that there were 61 chemical components and 90 potential targets in the compounds-targets network. We obtained 21 key targets, 154 signal pathways, and 382 biological processes in topological, GO, and KEGG enrichment analysis of the protein interaction network, and in the comprehensive analysis, it was found that Zuomua Decoction could reduce blood pressure by regulating renin angiotension aldosterone system, balancing the concentration of intracellular calcium and sodium ions and regulating vasoconstriction and relaxation. ACE, AGTR1, and ADRB2 were used as the carriers for molecular docking study on the components of Zuoma Decoction, and the results showed that the chemical components of Zuomua Decoction had a good binding activity with key targets. The purpose of this study is to provide ideas for the in-depth study of Zuoma Decoction in the treatment of hypertension, and provide scientific basis for its clinical rational application.
高血压是一种由一系列因素和载体功能障碍引起的慢性心血管系统疾病，属于藏医学“查龙病”范畴，致残率和死亡率较高。佐木扎汤是治疗查龙病的经典藏药，但其作用机制尚不明确。因此，本文基于网络药理学和分子对接技术，探讨了佐木扎汤治疗高血压的多成分、多靶点、多途径作用机制。首先，通过检索中药系统药理学数据库（TCMSP）、中国知网（CNKI）和万方数据库获取佐木扎汤的化学成分。利用BATMAN-TCM数据库预测佐木扎汤的潜在靶点，通过DisGeNET数据库获取高血压的靶点。取这两个靶点集的交集，得到佐木扎汤治疗高血压的潜在靶点，进而构建化学成分-靶点网络。其次，将交集靶点导入STRING数据库获取交集靶点的相互作用关系，在Cytoscape中构建佐木扎汤治疗高血压的蛋白质相互作用网络。采用拓扑学、基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析构建关键靶点-信号通路-生物学过程网络图，探讨佐木扎汤治疗高血压的作用机制。最后，选择关键靶点构建药效学鉴定模型，验证佐木扎汤治疗高血压的作用方式。结果显示，在化合物-靶点网络中有61种化学成分和90个潜在靶点。在蛋白质相互作用网络的拓扑学、GO和KEGG富集分析中，我们获得了21个关键靶点、154条信号通路和382个生物学过程，综合分析发现佐木扎汤可通过调节肾素血管紧张素醛固酮系统、平衡细胞内钙和钠离子浓度以及调节血管收缩和舒张来降低血压。选取血管紧张素转换酶（ACE）、血管紧张素Ⅱ受体1型（AGTR1）和β2肾上腺素能受体（ADRB2）作为佐木扎汤成分分子对接研究的载体，结果表明佐木扎汤的化学成分与关键靶点具有良好的结合活性。本研究旨在为深入研究佐木扎汤治疗高血压提供思路，为其临床合理应用提供科学依据。
