Investigation of the Therapeutic Effect of Total Alkaloids of Corydalis saxicola Bunting on CCl4-Induced Liver Fibrosis in Rats by LC/MS-Based Metabolomics Analysis and Network Pharmacology

Abstract

Liver fibrosis is a pathological result of liver injury that usually leads to a pathophysiological wound healing response. The total alkaloids of Corydalis saxicola Bunting (TACS) have been used for hepatoprotective effects on the liver. However, its exact therapeutic mechanisms of liver fibrosis are not yet well understood. To explore the potential anti-fibrosis mechanism of TACS, metabolomics coupled with network pharmacology were applied to reveal the underlying mechanisms. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with multivariate statistical analyses were performed to estimate changes in metabolic profiles. As a result, a total of 23 metabolites in rats with liver fibrosis were altered; of these, 11 had been downregulated and 12 had been upregulated compared with the control group. After TACS treatment, the levels of 13 metabolites were significantly restored compared with the CCl4-treated group, of which 4 metabolites were up-regulated and 9 metabolites were down-regulated. Many of these metabolites are involved in the bile acid metabolism, glutathione metabolism, tryptophan metabolism and purine metabolism. Then, three key targets, including cytochrome P450 family1 subfamily A member 1 (CYP1A1), ornithine decarboxylase 1 (OCD1) and monoamine oxidase Type B (MAOB) were predicted as potential therapeutic targets of TACS against liver fibrosis through network pharmacology analysis. Finally, palmatine, tetrahydropalmatine and dehydrocavidine were screened as potential active compounds responsible for the anti-fibrosis effect of TACS by molecular docking analysis. This study reveals that TACS exerted anti-fibrosis effects by regulating the liver metabolic pathway with multiple components and multiple targets, which is helpful to further clarify the hepatoprotective mechanisms of natural plant extracts.