Berberine regulates pulmonary inflammatory microenvironment and decreases collagen deposition in response to bleomycin-induced pulmonary fibrosis in mice.

Abstract

The purpose of this study was to explore the protective effect and potential mechanism of berberine on bleomycin (BLM)-induced fibrosis after lung injury in conjunction with network pharmacology. Berberine and pulmonary fibrosis prediction targets were collected for Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and so forth. A single intranasal dose of BLM (2.5 mg/kg) was administered to establish a model of fibrosis after lung injury, and berberine (50 mg/kg) was administered intraperitoneally daily for treatment. Network pharmacology results suggested that the mitogen-activated protein kinase (MAPK) signalling pathway may be a potential mechanism of berberine in delaying pulmonary fibrosis. The results of animal experiments showed that compared with the BLM group, after 14 days of berberine treatment, lung inflammatory cell aggregation was reduced and the expression levels of tumour necrosis factor-α (TNF-α), interleukin (IL)-8 and IL-6 were down-regulated in mice (p < 0.05); after 42 days of berberine treatment, the expression levels of transforming growth factor (TGF)-β1, platelet-derived growth factor-AB (PDGF-AB), hydroxyproline (HYP) and α-smooth muscle actin (α-SMA) were significantly down-regulated (p < 0.05), and the expression levels of total p38 MAPKα and p38 MAPKα (pT180/Y182) were down-regulated also (p < 0.05), inhibited collagen production and deposition, and increased the survival rate of mice to 70%. In conclusion, berberine attenuated inflammation mice, inhibited collagen production and showed some anti-pulmonary fibrosis potential in the MAPK signalling pathway.