Exploring the mechanism of Lianhuaqingwen (LHQW) in treating chronic bronchitis based on network pharmacology and experimental validation

• Published in: Respiratory research Vol. 25; no. 1; pp. 294 - 18
• Main Authors: Lin, Shaozhang, Wang, Shuan, Jiang, Qingping, Liu, Shaoyan, Liu, Shujing, Cai, Tonghui
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.08.2024; BMC
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Bronchitis; Bronchitis, Chronic - drug therapy; Bronchitis, Chronic - genetics; Bronchitis, Chronic - metabolism; Care and treatment; Chronic bronchitis; Diagnosis; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Evaluation; Humans; Lianhuaqingwen; Medicine, Chinese; Molecular docking; Molecular Docking Simulation - methods; Network pharmacology; Network Pharmacology - methods; Signal Transduction - drug effects; China; Lianhuaqingwen; Network pharmacology; Chronic bronchitis; Molecular docking
• ISSN: 1465-993X; 1465-9921; 1465-993X
• 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.