Network pharmacology prediction and molecular docking analysis reveal the mechanism of modified Bushen Yiqi formulas on chronic obstructive pulmonary disease.

BACKGROUND: The present study aimed to explore the mechanism of the modified Bushen Yiqi formula (MBYF) in the treatment of chronic obstructive pulmonary disease (COPD) based on network pharmacology and molecular docking. METHODS: First, the active ingredients and corresponding targets in MBYF were mined through the Traditional Chinese Medicine Systems Pharmacology database. Subsequently, Online Mendelian Inheritance in Man, DrugBank, and GeneCard were used to screen COPD-related targets. Cytoscape was used to construct a network of candidate components of MBYF in COPD treatment. The overlapping targets of COPD and MBYF were used to treat COPD, and then CytoHubba and CytoNAC plug-ins in Cytoscape were used for topology analysis to build the core network. In addition, core targets were used for Gene Ontology analysis and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes. Finally, AutoDock Vina software was used to conduct a molecular docking study on the core active ingredients and core targets to verify the above network pharmacological analysis. RESULTS: Seventy-nine active components of MBYF were screened and 261 corresponding targets were found. At the same time, 1307 related targets corresponding to COPD were screened and 111 overlapping targets were matched. By bioinformatics analysis, 10 core targets were identified, and subsequently, enrichment analysis revealed 385 BP, two CC, eight MF and 78 related signaling pathways. The binding of the core active components in MBYF to the core target was further verified by molecular docking, and all showed good binding. CONCLUSIONS: The active components of MBYF, such as quercetin, kaempferol, luteolin, and baicalein, may be the material basis for the treatment of chronic obstructive pulmonary disease. They affect the expression of inflammatory cells and inflammatory factors, protein phosphorylation, and smooth muscle hyperplasia through tumor necrosis factor, interleukin-17, mitogen-activated protein kinase, nuclear factor-kappa B and other signaling pathways.

Modified Bushen Yiqi Formula mitigates pulmonary inflammation and airway remodeling by inhibiting neutrophils chemotaxis and IL17 signaling pathway in rats with COPD.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic obstructive pulmonary disease (COPD) is a major global health concern characterized by pulmonary inflammation and airway remodeling. Traditional Chinese medicine, such as Modified Jiawei Bushen Yiqi Formula (MBYF), has been used as a complementary therapy for COPD in China. AIM OF THE STUDY: To investigate the therapeutic potential of MBYF in a rat model of COPD induced by cigarette smoke (CS) exposure and explore the underlying mechanism. MATERIALS AND METHODS: The COPD rat model was established through 24 weeks of CS exposure, with MBYF administration starting in the 9th week. Pulmonary function, histological analysis, inflammatory cell count and molecular assays were employed to assess the effects of MBYF on airway remodeling, pulmonary inflammation, neutrophils chemotaxis and the IL17 signaling pathway. RESULTS: MBYF treatment effectively delayed airway remodeling, as evidenced by improved pulmonary function parameters. Histological examination and bronchoalveolar lavage fluid analysis revealed that MBYF mitigated CS-induced pulmonary inflammation by reducing inflammatory cell infiltration. Pharmacological network analysis suggested that MBYF may act through the IL17 signaling pathway to regulate inflammatory responses. RNA-sequencing and molecular assays indicated that MBYF inhibited neutrophils chemotaxis through downregulating the CXCL1/CXCL5/CXCL8-CXCR2 axis, and suppressed IL17A, IL17F and its downstream cytokines, including IL6, TNFα, IL1ß, and COX2. Furthermore, MBYF inhibited the activation of NF-κB and MAPKs in the IL17 signaling pathway. CONCLUSION: MBYF exhibits potential as an adjunct or alternative treatment for COPD, effectively mitigating CS-induced pulmonary inflammation and airway remodeling through the inhibition of neutrophil chemotaxis and IL17 signaling pathway.