Zhang Qian, Yang Jie, Yang Chuanhua, Yang Xuesong, Chen Yongzhi
Department of Science and Technology Office, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Cardiology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Neurol. 2022 Mar 8;13:833922. doi: 10.3389/fneur.2022.833922. eCollection 2022.
In this study, we used the network pharmacology approach to explore the potential disease targets of the (EUO)- L. (TT) drug pair in the treatment of hypertension-associated neurovascular lesions and IS via the ferroptosis pathway.
We used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to search for the key active compounds and targets of the drug pair. Based on the GeneCards database, the relevant targets for the drug pair were obtained. Then, we performed the molecular docking of the screened core active ingredients and proteins using the DAVID database and the R AutoDock Vina software. Based on the GSE22255 dataset, these screened target proteins were used to build random forest (RF) and support vector machine (SVM) models. Finally, a new IS nomogram prediction model was constructed and evaluated.
There were 36 active compounds in the EUO-TT drug pair. CHRM1, NR3C1, ADRB2, and OPRD1 proteins of the neuroactive ligand-receptor interaction pathway interacted with the proteins related to the ferroptosis pathway. Molecular docking experiments identified 12 active ingredients of the drug pair that may tightly bind to those target proteins. We constructed a visual IS nomogram prediction model using four genes (CHRM1, NR3C1, ADRB2, and OPRD1). The calibration curve, DCA, and clinical impact curves all indicated that the nomogram model is clinically applicable and diagnostically capable. CHRM1, NR3C1, ADRB2, and OPRD1, the target genes of the four effective components of the EUO-TT drug pair, were considered as risk markers for IS.
The active ingredients of EUO-TT drug pair may act on proteins associated with the neuroactive ligand-receptor interaction pathway to regulate ferroptosis in vascular neurons cells, ultimately affecting the onset and progression of hypertension.
在本研究中，我们采用网络药理学方法，探讨（吴茱萸汤）-（天麻钩藤饮）药对通过铁死亡途径治疗高血压相关神经血管病变和缺血性脑卒中（IS）的潜在疾病靶点。
我们利用中药系统药理学数据库与分析平台搜索药对的关键活性成分和靶点。基于GeneCards数据库，获取药对的相关靶点。然后，使用DAVID数据库和R语言AutoDock Vina软件对筛选出的核心活性成分与蛋白质进行分子对接。基于GSE22255数据集，将这些筛选出的靶蛋白用于构建随机森林（RF）和支持向量机（SVM）模型。最后，构建并评估一个新的IS列线图预测模型。
吴茱萸汤-天麻钩藤饮药对中有36种活性化合物。神经活性配体-受体相互作用途径的CHRM1、NR3C1、ADRB2和OPRD1蛋白与铁死亡途径相关蛋白相互作用。分子对接实验确定药对中有12种活性成分可能与这些靶蛋白紧密结合。我们使用四个基因（CHRM1、NR3C1、ADRB2和OPRD1）构建了一个可视化的IS列线图预测模型。校准曲线、决策曲线分析（DCA）和临床影响曲线均表明列线图模型具有临床适用性和诊断能力。吴茱萸汤-天麻钩藤饮药对四种有效成分的靶基因CHRM1、NR3C1、ADRB2和OPRD1被视为IS的风险标志物。
吴茱萸汤-天麻钩藤饮药对的活性成分可能作用于与神经活性配体-受体相互作用途径相关的蛋白质，以调节血管神经细胞中的铁死亡，最终影响高血压的发生和发展。
