Metabolomics research on the hepatoprotective effect of cultured bear bile powder in α-naphthylisothiocyanate-induced cholestatic mice.

ABSTRACT

Natural bear bile powder (NBBP) is a famous traditional medicine and has been widely used in clinic. However, access to the sources of bear bile is restricted; hence, it is essential to discover new substitutes for NBBP. Cultured bear bile powder (CBBP) is transformed from chicken bile and contains main ingredients as to NBBP. In the present study, the effect and potential mechanism of action of CBBP on cholestatic liver injury in-naphthylisothiocyanate (ANIT)-induced mouse model was explored using metabolomics. CBBP treatment ameliorated impaired hepatic dysfunction and tissue damage that induced by ANIT. Metabolomics showed there were 28 different metabolites induced by ANIT as compared with control mice, and 18 of which was reversed by CBBP. Pathway analysis revealed that those 18 metabolites are mainly involved in bile acid (BA) biosynthesis and D-glutamine and D-glutamate metabolism. Further LC-MS/MS analysis showed that CBBP and NBBP both reduced serum and liver levels of BAs, but increased their biliary levels. Additionally, CBBP and NBBP upregulated expression of BA efflux transporters, Mrp2, Mrp3, and Mrp4, and metabolic enzymes, Cyp2b10 and Ugt1a1 of liver tissue of cholestatic mice, increased the BA excretion and metabolism. Moreover, CBBP and NBBP treatment upregulated GCLc/GCLm expression, and restored glutathione metabolism. In conclusion, the protective effects of CBBP against cholestatic liver injury were similar to those of NBBP. Mechanistically, both CBBP and NBBP reversed the disruption in homeostasis of BAs and glutathione, alleviating damage to hepatocytes.