Network pharmacology analysis uncovers the effect on apoptotic pathway by Bu-Fei formula for COPD treatment

Ethnopharmacological relevance: The Bu-Fei formula (BFF) has a positive effect on chronic obstructive pulmonary disease (COPD). However, its therapeutic mechanisms against COPD remain unknown. Aim of the study: To explore BFF's therapeutic effect on COPD and pharmacological mechanisms. Materials and methods: First, the effect of BFF on rats with COPD was studied. Rats were randomly assigned to the blank, COPD, BFF treatment, and aminophylline (APL) treatment groups. From weeks 1-8, the COPD model was established by Klebsiella pneumoniae (KP) and cigarette smoke. Then, rats were given corresponding treatment for 8 weeks. The lung function of the rats was analyzed by whole-body plethysmography and pulmonary function testing, lung histopathology by electron microscopy and hematoxylin and eosin staining, and protein levels by immunohistochemistry. Next, the key components and targets of BFF in COPD were screened by network pharmacology analysis. Finally, the possible mechanism was verified through molecular docking and in vivo experiments. Results: BFF significantly improved lung function and lung histopathology in COPD rats and inhibit inflammation and collagen deposition in lung tissues. Also, 46 bioactive compounds and 136 BFF targets related to COPD were identified; among them, 3 compounds (quercetin, luteolin, and nobiletin) and 6 core targets (Akt1, BCL2, NF-kappa B p65, VEGFA, MMP9, and Caspase 8) were the key molecules associated with the mechanisms of BFF. The target enrichment analysis suggested that BFF's mechanisms might involve the apoptosis-related pathway; this possibility was supported by the molecular docking data. Lastly, BFF was indicated to increase the expression of core target genes and the production of apoptosis-related proteins. Conclusions: BFF affects COPD by regulating the apoptosis-related pathways and targets.