Graduate School of Heilongjiang University of Chinese Medicine, Harbin, 150040 Heilongjiang, China.
Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, 150040 Heilongjiang, China.
Biomed Res Int. 2022 Aug 22;2022:3353464. doi: 10.1155/2022/3353464. eCollection 2022.
Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD's pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.
原发性高血压被认为是一种病因多样、病理机制复杂、呈进行性变化的疾病。葛根降压汤（GJD），专利公开号为 CN114246896A，旨在治疗原发性高血压。它包含六种植物药，但作用机制尚不清楚。我们利用网络药理学预测 GJD 治疗原发性高血压的活性成分、靶点和信号通路。我们还通过分子对接和动物实验研究了其潜在的分子机制。中药系统药理学数据库和分析平台（TCMSP）、蛋白质数据库（UniProt）和文献综述用于鉴定 GJD 药效的活性成分和相关靶点。基因数据库（GeneCards）、在线孟德尔遗传数据库（OMIM）、治疗靶点数据库（TTD）和药物数据库（DrugBank）用于鉴定高血压相关靶点。基于设计交集靶点的 Venn 图，获得 214 个交集靶点，并使用 STRING 数据平台和 Cytoscape 软件确定 35 个治疗高血压的关键靶点。关键靶点的京都基因与基因组百科全书（KEGG）富集分析表明，GJD 治疗高血压的相关分子作用途径包括 Toll 样受体、MAPK、PI3K-Akt 和肾素-血管紧张素信号通路。使用 Cytoscape 软件创建了 GJD 活性成分-关键靶点-通路连接图，并选择了 11 种重要的活性成分。然后进行分子对接，验证 GJD 治疗原发性高血压的关键靶点和关键活性成分的结合活性。研究结果表明，葛根素与 AGTR1、AKT1，丹参酮 IIA 与 EDNRA，大豆苷元与 MAPK14，熊果酸与 MAPK8，隐丹参酮与 CHRM2 结合活性较高，AGTR1 被选为实验验证的靶基因。采用 HPLC 鉴定 5 种活性成分。在高盐大鼠实验中，GJD 可能通过抑制肾素-血管紧张素途径的激活，降低肾脏和胸主动脉 AGTR1 的表达，增加 eNOS 的表达，从而降低收缩压和舒张压。
