Abstract

Pulmonary fibrosis (PF) is one of the pathologic changes in COVID-19 patients in convalescence, and it is also a potential long-term sequela in severe COVID-19 patients. Qimai Feiluoping decoction (QM) is a traditional Chinese medicine formula recommended in the Chinese national medical program for COVID-19 convalescent patients, and PF is one of its indications. Through clinical observation, QM was found to improve the clinical symptoms and pulmonary function and reduce the degree of PF of COVID-19 convalescent patients. To further explore the pharmacological mechanisms and possible active components of QM in anti-PF effect, UHPLC/Q-TOF-MS was used to analyze the composition of the QM extract and the active components that can be absorbed into the blood, leading to the identification of 56 chemical compounds and 10 active components. Then, network pharmacology was used to predict the potential mechanisms and targets of QM; it predicted that QM exerts its anti-PF effects via the regulation of the epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) degradation, and TGF-β signaling pathway. Finally, TGF-β1–induced A549 cells were used to verify and explore the pharmacological effects of QM and found that QM could inhibit the proliferation of TGF-β1–induced A549 cells, attenuate EMT, and promote ECM degradation by inhibiting the TGF-β/Smad3 pathway.

Highlights

  • Many interstitial lung diseases, such as idiopathic interstitial pneumonias and acute lung injury, can progress to pulmonary fibrosis (PF)

  • 10 batches of Qimai Feiluoping decoction (QM) samples were analyzed, and similarity values of 0.983–0.999 were obtained by comparing with the reference spectrum, which indicated that the QM formula was reproducible (Figures 1C,D)

  • The inhibitory effects of QM on extracellular matrix (ECM) accumulation were the strongest at a concentration of 500 μg/ml (Figures 6B,C). These results suggested that QM stimulates ECM degradation in TGF-β1–induced A549 cells

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Summary

Introduction

Many interstitial lung diseases, such as idiopathic interstitial pneumonias and acute lung injury, can progress to pulmonary fibrosis (PF). Idiopathic PF (IPF) is a devastating, irreversible, and chronic progressive form of PF, and lung transplantation is the only treatment that can change the outcome of IPF patients (Richeldi et al, 2017). PF is a pathological phenomenon in the development of various respiratory diseases, such as viral pneumonia and chronic obstructive pulmonary disease (COPD) (Meyer, 2017). The Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Asselah et al, 2021), has become a worldwide pandemic, infecting over 222 million people and killing more than 4.9 million people as of October 2021. The absence of SARS-CoV-2 nucleic acid in COVID-19 patients does not guarantee complete recovery, especially in severe and critical patients. There is an urgent need to develop novel therapeutic strategies to delay the progressive stages of PF and deal with the possible arrival of post-COVID-19–related PF

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