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.

天然熊胆粉（NBBP）是一种著名的传统药物，已在临床中广泛使用。但是，接触熊胆的来源受到限制；因此，找到新的NBBP替代品至关重要。培养的熊胆粉（CBBP）是从鸡胆中转化而来的，其中包含有关NBBP的主要成分。在本研究中，使用代谢组学研究了CBBP对胆汁淤积性肝损伤的萘基异硫氰酸酯（ANIT）诱导的小鼠模型的作用及其潜在机制。CBBP治疗改善了由ANIT引起的肝功能障碍和组织损伤。代谢组学显示，与对照组相比，ANIT诱导了28种不同的代谢产物，其中18种被CBBP逆转。途径分析表明，这18种代谢物主要参与胆汁酸（BA）的生物合成以及D-谷氨酰胺和D-谷氨酸的代谢。进一步的LC-MS / MS分析表明，CBBP和NBBP均降低了BAs的血清和肝脏水平，但增加了其胆汁水平。此外，CBBP和NBBP上调了BA外排转运蛋白的表达，MRP2，MRP3和MRP4，以及代谢酶，Cyp2b10和UGT1A1胆汁淤积小鼠的肝组织，增加了BA排泄和代谢。此外，CBBP和NBBP处理上调了GCLc / GCLm表达，并恢复了谷胱甘肽的代谢。总之，CBBP对胆汁淤积性肝损伤的保护作用与NBBP相似。从机理上讲，CBBP和NBBP均可逆转BA和谷胱甘肽体内稳态的破坏，从而减轻对肝细胞的损害。