Department of Pathology, Department of Anesthesiology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, People's Republic of China.
Key Laboratory of Sports Technique, Tactics and Physical Function of General Administration of Sport of China, Scientific Research Center, Guangzhou Sport University, Guangzhou, 510500, People's Republic of China.
Respir Res. 2024 Aug 2;25(1):294. doi: 10.1186/s12931-024-02927-7.
Lianhuaqingwen (LHQW) has been used in the treatment of chronic bronchitis, but the precise mechanism through which LHQW exhibits its anti-inflammatory effects in this context is not yet fully understood. The aim of this study was to investigate the active ingredients and signaling pathways responsible for LHQW's effectiveness in managing chronic bronchitis.
The research leveraged the TCMSP database to determine the active compounds and drug targets of LHQW. In parallel, the GeneCards, DrugBank, and PharmGkb databases were used to uncover targets pertinent to chronic bronchitis. To discern the potential mechanisms by which LHQW's active ingredients might treat chronic bronchitis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Network pharmacology facilitated the construction of a drug-active ingredient-disease target network, aiding in forecasting the core targets for chronic bronchitis treatment by LHQW. Subsequently, molecular docking techniques alongside in vitro experiments were applied to confirm the interactions between the active ingredients and the primary targets.
A total of 157 active ingredients, 225 potential drug targets, and 594 bronchitis-related targets were derived from various databases. Following this, 76 potential gene targets were pinpointed by integrating drug and related targets. GO and KEGG enrichment analyses were employed to identify key pathways involved in LHQW's mechanism for treating chronic bronchitis. By constructing a protein-protein interaction (PPI) network for the 76 potential gene targets, four core targets (TNF, IL6, IFNG, and STAT3) were identified as primarily involved in responses to lipopolysaccharide, the TNF pathway, and the JAK-STAT pathway. Molecular docking results revealed a favorable affinity between multiple active ingredients of LHQW and the four core targets, suggesting that the therapeutic effects are mediated through the inhibition of inflammatory responses and signaling pathways. Interestingly, quercetin, an active ingredient of LHQW, was observed to bind to all four core targets simultaneously. Furthermore, cell experiment and western blot analysis indicated that both LHQW and quercetin exhibit anti-inflammatory effects by targeting the four core proteins and the JAK-STAT pathways.
This research emphasizes the diverse active ingredients, targets, channels, and pathways of LHQW in the treatment of chronic bronchitis, providing important perspectives for the creation of novel therapeutic drugs and clinical uses.
连花清瘟（LHQW）已被用于治疗慢性支气管炎，但 LHQW 在这种情况下发挥抗炎作用的确切机制尚不完全清楚。本研究旨在探讨 LHQW 有效治疗慢性支气管炎的活性成分和信号通路。
研究利用 TCMSP 数据库确定 LHQW 的活性化合物和药物靶点。同时，利用 GeneCards、DrugBank 和 PharmGkb 数据库揭示与慢性支气管炎相关的靶点。为了确定 LHQW 的活性成分治疗慢性支气管炎的潜在机制，进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。网络药理学有助于构建药物-活性成分-疾病靶标网络，有助于预测 LHQW 治疗慢性支气管炎的核心靶标。随后，应用分子对接技术和体外实验证实活性成分与主要靶标的相互作用。
从多个数据库中提取了 157 种活性成分、225 个潜在药物靶点和 594 个与支气管炎相关的靶点。在此基础上，通过整合药物和相关靶点，确定了 76 个潜在基因靶点。GO 和 KEGG 富集分析用于鉴定 LHQW 治疗慢性支气管炎机制中涉及的关键途径。通过构建 76 个潜在基因靶点的蛋白质-蛋白质相互作用（PPI）网络，鉴定出四个核心靶点（TNF、IL6、IFNG 和 STAT3），主要涉及对脂多糖的反应、TNF 途径和 JAK-STAT 途径。分子对接结果表明，LHQW 的多种活性成分与四个核心靶点之间具有良好的亲和力，提示治疗作用是通过抑制炎症反应和信号通路介导的。有趣的是，LHQW 的活性成分槲皮素同时与四个核心靶点结合。此外，细胞实验和 Western blot 分析表明，LHQW 和槲皮素均通过靶向四个核心蛋白和 JAK-STAT 通路发挥抗炎作用。
本研究强调了 LHQW 治疗慢性支气管炎的多种活性成分、靶点、通道和途径，为新型治疗药物的研发和临床应用提供了重要视角。
Zotero 插件
