Liver fibrosis is a severe health problem, threatening the life quality and causing death, raising great concerns worldwide. Shi-Wei-Gan-Ning-Pill (SWGNP) is a traditional Tibetan recipe used to treat hepatic
injuries; however, its hepatoprotective mechanism has not yet fully clarified. In this study, histological staining, biochemical assays, and elements determination were applied to evaluate the anti-fibrotic efficacy of SWGNP on a
carbon tetrachloride (CCl4) induced hepato-
fibrosis rat model. NMR-based metabolomics combined with orthogonal partial least squares-discriminant analysis (OPLS-DA), canonical regression analysis, and correlation networks analysis was used to characterize the potential
biomarkers as well as metabolic pathways associated with the hepatoprotective activity of SWGNP. The results showed that SWGNP could significantly attenuate the pathological changes and decrease the levels of
fibrosis markers (ColIV, HA, LN, and PCIII), and regulate the disordered elements distribution. Multivariate analysis and correlation network analysis revealed that SWGNP could protect rats against CCl4-induced
liver fibrosis through anti-oxidation, repairing the impaired energy metabolisms and reversing the disturbed
amino acids and
nucleic acids metabolisms. In conclusion, this integrated metabolomics approach provided new insights into the mechanism of the hepatoprotective effect of SWGNP in
liver fibrosis disease.