Sun Rui, Xu Gonghao, Gao Dongyang, Ding Qi, Shi Yuanyuan
School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.
Shenzhen Research Institute, Beijing University of Chinese Medicine, Shenzhen 518118, China.
Evid Based Complement Alternat Med. 2021 Dec 20;2021:9033842. doi: 10.1155/2021/9033842. eCollection 2021.
Asthma, characterized by the continuous inflammatory response caused by a variety of immune cells, is one of the most common chronic respiratory diseases worldwide. Relevant clinical trials proved that the traditional Chinese medicine formula Guizhi Decoction (GZD) had multitarget and multichannel functions, which might be an effective drug for asthma. However, the effective ingredients and mechanisms of GZD against asthma are still unclear. Therefore, network pharmacology, molecular docking, and cell experiments were performed to explore the antiasthma effects and potential mechanisms of GZD. First, we applied the TCMSP database and literature to obtain the bioactivated ingredients in GZD. SwissTargetPrediction, TCMSP, GeneCards, OMIM, PharmGkb, TTD, DrugBank, and STRING database were used to get core genes. In addition, the key pathways were analyzed by the DAVID database. Molecular docking was used to predict whether the important components could act on the core target proteins directly. Finally, qPCR was carried out to verify the network pharmacology results and the possible mechanisms of GZD in the treatment of asthma. We collected 134 active ingredients in GZD, 959 drug targets, and 3223 disease targets. 431 intersection genes were screened for subsequent analysis. Through GO and KEGG analyses, enriched pathways related to inflammation and immune regulation were presented. Through the qPCR method to verify the role of essential genes, we found that GZD had an excellent anti-inflammatory effect. Direct or indirect inhibition of MAPK and NF-B pathways might be one of the crucial mechanisms of GZD against asthma. GZD might be a promising potential drug for the treatment of asthma. This article provided a reference for the clinical application of GZD.
哮喘是由多种免疫细胞引起的持续炎症反应所导致的,是全球最常见的慢性呼吸道疾病之一。相关临床试验证明,中药方剂桂枝汤(GZD)具有多靶点、多途径作用,可能是治疗哮喘的有效药物。然而,GZD抗哮喘的有效成分和作用机制仍不清楚。因此,进行了网络药理学、分子对接和细胞实验,以探讨GZD的抗哮喘作用及潜在机制。首先,我们应用中药系统药理学数据库与分析平台(TCMSP)数据库和文献获取GZD中的生物活性成分。利用瑞士靶点预测数据库(SwissTargetPrediction)、TCMSP、基因卡片数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、药物基因组学知识库(PharmGkb)、治疗靶点数据库(TTD)、药物银行数据库(DrugBank)和STRING数据库获取核心基因。此外,通过DAVID数据库分析关键通路。利用分子对接预测重要成分是否能直接作用于核心靶蛋白。最后,进行qPCR验证网络药理学结果及GZD治疗哮喘的可能机制。我们收集到GZD中的134种活性成分、959个药物靶点和3223个疾病靶点。筛选出431个交集基因用于后续分析。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)分析,呈现了与炎症和免疫调节相关的富集通路。通过qPCR方法验证关键基因的作用,我们发现GZD具有良好的抗炎作用。直接或间接抑制丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)通路可能是GZD抗哮喘的关键机制之一。GZD可能是一种有前途的治疗哮喘的潜在药物。本文为GZD的临床应用提供了参考。