Serum metabolomic research of the anti-pulmonary fibrosis effects of Shuangshen Pingfei Formula on bleomycin-induced pulmonary fibrosis rats

•An integrative approach based on GC-MS and UPLC-QE-MS metabolomics data as a comprehensive strategy to search potential pulmonary fibrosis (PF) biomarkers.•PCA and OPLS-DA were applied to find out the differences between the control (NS), model group (PF), and treat group (SSPF) to assess the influence of SSPF on the metabolic pattern.•The metabolic profile was investigated in the process of the occurrence and development of PF.•After SSPF treatment, the disorder of lipid, amino acid metabolism was regulated. Serine, proline, glutamine, dihydroxybenzoic acid, 4-guanidinobutyric acid, phosphatidylethanolamine, lecithin and 9,10-epoxyoctadecene acids may be useful as biomarkers of the anti-fibrosis effect of SSPF. Our previous studies showed that Shuangshen Pingfei Formula (SSPF) exhibited anti-fibrosis effect, but its biochemical changes at the metabolic level remain unclear. In this study, an integrative approach of gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS)-based non-targeted metabolomics and multivariate statistical analysis was employed to explore the metabolic changes of serum samples from different stages of bleomycin-induced pulmonary fibrosis (PF) rats (PFRs: M7, M14, M21 and M28) treated with SSPF extracts. Potential biomarkers for PF were screened. Benzenebutanoic acid, pyroglutamic acid, cholic acid, 1-monopalmitin, succinic acid and palmitoleic acid may be potential biomarkers of the early inflammation stage of PF (M7-M14). 3,4-dimethylbenzoic acid, glutamic acid, glycine, proline, serine, taurine, etc. may be potential biomarkers for the advanced pulmonary fibrosis stage (M21-M28) of PF. The disturbance was mainly related to the disorder of lipid, amino acid metabolism. After SSPF treatment, the disorder was regulated and 67 metabolites were restored to a certain extent. Serine, proline, glutamine, 4-guanidinobutyric acid, phosphatidylethanolamine, lecithin and 9,10-epoxyoctadecene acids may be useful as biomarkers of the anti-fibrosis effect of SSPF.