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基于系统药理学研究确定中药附子与半夏配伍在慢性阻塞性肺疾病中的药理机制

Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study.

作者信息

Ni Kaiwen, Cai Xiaolu, Chen Yaling, Zhou Linshui, Chen Ruilin, Zheng Suqun, Wang Zhen

机构信息

The First Clinical College of Zhejiang Chinese Medical University, Hangzhou, China.

The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Evid Based Complement Alternat Med. 2020 Dec 31;2020:8365603. doi: 10.1155/2020/8365603. eCollection 2020.

Abstract

(Fuzi) and (Banxia) are among the 18 incompatible medications that are forbidden from use in one formulation. However, there is increasing evidence implying that this prohibition is not entirely correct. According to the theory of Chinese traditional medicine, they can be used for the treatment of chronic obstructive pulmonary disease (COPD). Thus, we analyzed the possible approaches for the treatment of COPD using network pharmacology. The active compounds of Fuzi and Banxia (FB) were collected, and their targets were identified. COPD-related targets were obtained by analyzing the differentially expressed genes between COPD patients and healthy individuals, which were expressed using a Venn diagram of COPD and FB. Protein-protein interaction data and network regarding COPD and drugs used were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted. The gene-pathway network was constructed to screen the key target genes. In total, 34 active compounds and 47 targets of FB were identified; moreover, 7,153 differentially expressed genes were identified between COPD patients and healthy individuals. The functional annotations of target genes were found to be related to mechanisms such as transcription, cytosol, and protein binding; furthermore, 68 pathways including neuroactive ligand-receptor interaction, Kaposi sarcoma-associated herpesvirus infection, apoptosis, and measles were significantly enriched. FOS CASP3, VEGFA, ESR1, and PTGS2 were the core genes in the gene-pathway network of FB for the treatment of COPD. Our results indicated that the effect of FB against COPD may involve the regulation of immunological function through several specific biological processes and their corresponding pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of herb-opponents FB.

摘要

附子与半夏属于十八反,在同一方剂中禁止使用。然而,越来越多的证据表明这一禁令并不完全正确。根据中医理论,它们可用于治疗慢性阻塞性肺疾病(COPD)。因此,我们运用网络药理学分析了治疗COPD的可能方法。收集了附子和半夏(FB)的活性成分,并确定了它们的靶点。通过分析COPD患者与健康个体之间的差异表达基因获得COPD相关靶点,并使用COPD与FB的韦恩图进行展示。获取了蛋白质-蛋白质相互作用数据以及关于COPD和所用药物的网络。进行了基因本体论和京都基因与基因组百科全书通路分析。构建基因-通路网络以筛选关键靶基因。共鉴定出34种FB的活性成分和47个靶点;此外,还鉴定出COPD患者与健康个体之间7153个差异表达基因。发现靶基因的功能注释与转录、胞质溶胶和蛋白质结合等机制有关;此外,包括神经活性配体-受体相互作用、卡波西肉瘤相关疱疹病毒感染、细胞凋亡和麻疹在内的68条通路显著富集。FOS、CASP3、VEGFA、ESR1和PTGS2是FB治疗COPD的基因-通路网络中的核心基因。我们的结果表明,FB对COPD的作用可能涉及通过若干特定生物学过程及其相应通路调节免疫功能。本研究展示了网络药理学在评估相反药对FB的作用机制和分子靶点方面的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1f3/7790578/1192dfa3eb32/ECAM2020-8365603.001.jpg

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