Integrating network pharmacology and transcriptomic validation to investigate the efficacy and mechanism of Mufangji decoction preventing lung cancer

Abstract

Ethnopharmacological relevance: Mufangji decoction (MFJD), a famous traditional Chinese medicine formula in Synopsis of Golden Chamber (Jingui yaolue), has been utilized to treat cough and asthma and release chest pain over 2000 years in China. Chinese old herbalist doctor use MFJD to treat lung cancer and cancerous pleural fluid, but the preventive effect of MFJD on lung cancer and the underlying mechanism are indefinite.

Aim of the study: The goal of this study is to explore the efficacy and mechanism of Mufangji decoction preventing lung cancer referring to the traditional use.

Materials and methods: Tumor allograft experiment and host versus tumor experiment were used to observe the direct anti-tumor effect and indirect anti-tumor immune effect, the mouse lung carcinogenic model was used to evaluate the dose-response and the preventive effect of MFJD on lung cancer. The active ingredients of MFJD were obtained by UPLC-MS/MS. The potential targets of MFJD were screened by network pharmacology and transcriptomics. The therapeutic targets and pathways of MFJD on lung cancer were obtained by protein-protein interaction, molecular docking and David database. The predicted results were verified in vitro and in vivo.

Results: MFJD could significantly prevent tumor growth in host versus tumor experiment but could not in tumor allograft experiment, indicating an anti-tumor immune effect against lung cancer. MFJD could reduce lung nodules with a dose-response in mouse lung carcinogenic model. Myeloperoxidase (MPO) was selected as the core target due to the highest degree value in Protein-Protein interaction network and had potently binding activity to sinomenine and dehydrocostus lactone in molecular docking. In vivo, MPO-expressed neutrophils are negatively correlated with lung cancer progression and MFJD could promote the neutrophil-related immune surveillance. In vitro, sinomenine and dehydrocostus lactone could promote neutrophil phagocytosis, MPO and ROS production in a dose dependent manner. The major compounds from MFJD were identified to regulate 36 targets for lung cancer prevention by UPLC-MS/MS, network pharmacology and transcriptomics. David database exhibited that MFJD plays an important role in immunoregulation by modulating 4 immune-related biological processes and 3 immune-related pathways.

Conclusions: MFJD prevents lung cancer by mainly promoting MPO expression to maintain neutrophil immune surveillance, its key compounds are sinomenine and dehydrocostus lactone.

Keywords: Immunity; Lung cancer; Mufangji decoction; Network pharmacology; Transcriptomics.