Jingfang Granules () alleviates bleomycin-induced acute lung injury through regulating PI3K/Akt/mTOR signaling pathway

Abstract

Ethnopharmacological relevance: Acute lung injury is a kind of clinical emergency severe syndrome which might trigger acute respiratory distress syndrome. Jingfang Granules () is a traditional Chinese medicine which has been proven to improve acute lung injury induced by bleomycin through inhibiting recruitment and overactive of inflammation. However, the potential mechanisms are still not well evaluated.

Aim of study: The aim of this study was to evaluate the protective function of Jingfang Granules on bleomycin caused acute lung injury and further discuss the potential pharmacological mechanisms.

Materials and methods: C57BL/6J mice were intratracheal injected bleomycin to induce model with acute lung injury. The protective impact of Jingfang Granules on acute lung injury and lung fibrosis triggered by bleomycin were evaluated through detecting mice body weight, lung appearance, lung index, and histopathology. The potential pharmacological mechanism of Jingfang Granules in treating acute lung injury was further elucidated by the methods of network pharmacology, proteomics, metabolomics, as well as western blot. Additionally, the network pharmacology analysis and molecular docking technology were integrated to investigate the targets of Jingfang Granules improving acute lung injury.

Results: Our results indicated that Jingfang Granules effectively protected mice from acute lung injury induced by bleomycin, which was confirmed by higher body weight, lower pulmonary edema and lung index, and improved pathology and fibrosis of lung tissue compared to model group. Proteomics, western blot, and metabolomics were integrated and the results confirmed that Jingfang Granules regulated the Glycolysis/Gluconogenesis and Pyruvate metabolism through downregulating the PI3K/Akt/mTOR signaling pathway. The network pharmacology analysis and molecular docking technology results showed that the targets of Jingfang Granules for treating acute lung injury were enriched in the PI3K/Akt signaling pathway, which included 7 target proteins such as MAPK1, MAPK3, JAK2, HRAS, EGFR, PIK3R1, and PIK3CA.

Conclusion: This study indicates that Jingfang Granules displays a markedly protective effect on acute lung injury caused by bleomycin through downregulating PI3K/Akt/mTOR signaling pathway, which in turn regulates Glycolysis/Gluconogenesis and Pyruvate metabolism.

Keywords: Acute lung injury; Glycolysis; Jingfang granules; PI3K/Akt/mTOR signaling pathway; Pulmonary fibrosis.