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Medical Science Monitor Basic Research


eISSN: 1643-3750

Effect of Fluorofenidone Against Paraquat-Induced Pulmonary Fibrosis Based on Metabolomics and Network Pharmacology

Feiya Jiang, Tongtong Wang, Sha Li, Yu Jiang, Zhuo Chen, Wen Liu

Department of Pharmacy, The First Hospital Affiliated with Hunan Normal University, Changsha, Hunan, China (mainland)

Med Sci Monit 2021; 27:e930166

DOI: 10.12659/MSM.930166

Available online: 2021-02-05

Published: 2021-04-01


BACKGROUND: Fluorofenidone (AKF-PD) is an anti-fibrotic small-molecule compound. Its mechanism of action on paraquat (PQ)-induced pulmonary fibrosis is still unclear.
MATERIAL AND METHODS: Forty-eight SD rats were divided into 4 groups: control group, PQ group, PQ+AKF-PD group, and AKF-PD group. The pathological changes of lung tissues were observed by Masson and HE staining. The UPLC-QTOF-MS analysis was performed to detect the differences in metabolites among groups, then the possible mechanisms of the anti-pulmonary fibrosis effects of fluorofenidone were further revealed by network pharmacology analysis. Biological methods were used to verify the results of the network pharmacology analysis.
RESULTS: The results showed that fluorofenidone treatment significantly alleviated paraquat-induced pulmonary fibrosis. Metabolomics analysis showed that 18 metabolites were disordered in the serum of paraquat-poisoned rats, of which 13 were restored following fluorofenidone treatment. Network pharmacology analysis showed that the drug screened a total of 12 targets and mainly involved multiple signaling pathways and metabolic pathways to jointly exert anti-pulmonary fibrosis effects. Autophagy is the main pathway of fluorofenidone in treatment pulmonary fibrosis. The western blot results showed that fluorofenidone upregulated the expression of LC3-II/I and E-cadherin, and downregulated the expression of p62, alpha-SMA, and TGF-ß1, which validated that fluorofenidone could inhibit the development of paraquat-induced pulmonary fibrosis by increasing autophagy.
CONCLUSIONS: In conclusion, metabolomics combined with network pharmacology research strategy revealed that fluorofenidone has a multi-target and multi-path mechanism of action in the treatment of pulmonary fibrosis.

Keywords: idiopathic pulmonary fibrosis, Metabolic Networks and Pathways, Metabolomics, Paraquat, Protein Interaction Maps