Multi-omics analysis reveals the mechanisms of action and therapeutic regimens of traditional Chinese medicine, Bufei Jianpi granules: Implication for COPD drug discovery

Chronic Obstructive Pulmonary Disease (COPD) is a serious public health challenge in the world. According to the treatment instructions by Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020, bronchiectasis combine with inhaled corticosteroids and long-acting anti-muscarinic agents were recommended as the main prescription. However, this symptomatic treatment still has ineluctable limits because it ignored the most pathogenesis mechanism of COPD. As an alternative traditional Chinese medicine (TCM) for COPD, Bufei Jianpi granules (BJG) can reduce the frequency and duration of acute exacerbation in COPD patients and improve their quality of life. The evidence demonstrated BJG acts as therapeutics that retarding the airway remodeling process, eliminating phlegm, thrombolysis and improving mitochondrial function. However, the detailed molecular mechanism is still urgently revealed. In this study, we aim to find out the active pharmacodynamic ingredients and reveal the treatment mechanism of active pharmacodynamic ingredients. Based on the pharmacodynamic evaluation and chemomic profiling of BJG in COPD rats, an integrated multi-omics analysis was performed, including molecular networking, metabonomics, proteomics and bioinformatics. Moreover, focus on the active compounds, we verified the molecular core mechanism by molecular biology methods. Pachymic acid, shionone, peiminine and astragaloside A was verified as therapeutic agents for improving the condition of COPD by acting on the EGFR, ERK1, PAI-1 and p53 target, respectively. In this study, our findings indicated that some compounds in BJG alleviates the pathological process of COPD, which is related to regulating lung function, mucus production, pulmonary embolism and energy metabolism and this will be a benefit complementary to GOLD guidelines.