He Wenjun, Liu Chunli, Li Xuanyi, Zhong Bihua, Jiang Qian, Lai Ning, Xiong Yuanhui, Feng Weici, Chen Yilin, Zhou Dansha, Li Defu, Lu Wenju, Aman Jurjan, Bogaard Harm Jan, Wang Jian, Chen Yuqin
State Key Laboratory of Respiratory Diseases, National Center for Respiratory Medicine, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong China.
PHEniX laboratory, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis Amsterdam UMC location Vrije Universiteit Amsterdam Amsterdam The Netherlands.
Pulm Circ. 2024 Jul 21;14(3):e12414. doi: 10.1002/pul2.12414. eCollection 2024 Jul.
Chronic obstructive pulmonary disease (COPD) is a persistent and progressive disorder characterized by airway or alveolar abnormalities, commonly leading to pulmonary hypertension (PH). This clinical observational study investigates the therapeutic mechanisms of Bufei Huoxue capsules (BHC) in treating PH in patients with COPD-linked PH (COPD-PH) using network pharmacology and molecular docking methods, and assesses the therapeutic efficacy and safety of BHCs. The active compounds and their target proteins in BHCs were sourced from the Traditional Chinese Medicine Systems Pharmacology database, with additional target proteins derived from the GeneCards and OMIM databases. An active network was constructed using Cytoscape 3.7.1, and interaction networks were established. Intersecting targets underwent Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Metascape database. Network pharmacology and molecular docking studies demonstrated favorable binding affinities of BHC active ingredients, such as quercetin, bavachalcone, and isobavachin, for key targets including PTGS1, ESR1, and PTGS2. Gene Ontology enrichment analysis highlighted the involvement of these targets in processes such as the positive regulation of locomotion, the transmembrane receptor protein tyrosine kinase signaling pathway, and peptidyl-tyrosine phosphorylation. KEGG pathway analysis indicated their roles in pathways related to cancer, AGE-RAGE signaling in diabetic complications, and prostate cancer. BHCs exhibit therapeutic effects on COPD-PH through multi-component, multi-target, and multi-pathway interactions. This clinical observational study confirms the efficacy and safety of BHCs in improving cardiac and pulmonary functions, enhancing exercise tolerance, and elevating the quality of life in patients with COPD-PH.
慢性阻塞性肺疾病（COPD）是一种持续性、进行性疾病，其特征为气道或肺泡异常，通常会导致肺动脉高压（PH）。本临床观察性研究采用网络药理学和分子对接方法，探讨补肺活血胶囊（BHC）治疗慢性阻塞性肺疾病相关性肺动脉高压（COPD-PH）患者肺动脉高压的治疗机制，并评估BHC的治疗效果和安全性。BHC中的活性化合物及其靶蛋白来源于中药系统药理学数据库，另外的靶蛋白则来源于GeneCards和OMIM数据库。使用Cytoscape 3.7.1构建活性网络，并建立相互作用网络。利用Metascape数据库对交集靶点进行基因本体论（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析。网络药理学和分子对接研究表明，BHC活性成分，如槲皮素、补骨脂查尔酮和异补骨脂查尔酮，与包括PTGS1、ESR1和PTGS2在内的关键靶点具有良好的结合亲和力。基因本体论富集分析突出了这些靶点参与运动的正向调节、跨膜受体蛋白酪氨酸激酶信号通路和肽基酪氨酸磷酸化等过程。KEGG通路分析表明它们在与癌症、糖尿病并发症中的AGE-RAGE信号传导以及前列腺癌相关的通路中发挥作用。BHC通过多成分、多靶点和多途径相互作用对COPD-PH具有治疗作用。本临床观察性研究证实了BHC在改善COPD-PH患者心肺功能、提高运动耐力和提升生活质量方面的疗效和安全性。
