Xiaoyan lidan formula ameliorates α-naphthylisothiocyanate-induced intrahepatic cholestatic liver injury in rats as revealed by non-targeted and targeted metabolomics.

Intrahepatic cholestasis is a clinical syndrome of liver damage with systemic circulation and intrahepatic accumulation of excessive toxic bile acids without effective therapeutic methods so far. Xiaoyan Lidan Formula (XYLDF), a traditional Chinese prescription, has long been clinically applied for hepatobiliary disorders due to cholestasis. But its mechanism remains unknown. In this study, a non-targeted metabolomics approach based on UHPLC-Q-TOF-MS/MS combined with a bile acids (BAs) - targeted metabolomics approach based on UHPLC-MS/MS were performed to elucidate the functional mechanisms of XYLDF on α-naphthylisothiocyanate(ANIT)-induced intrahepatic cholestasis rats. The results showed that a total of 39 endogenous metabolites with significant difference (VIP > 1.00, P < 0.05) were identified as biomarkers of ANIT-induced intrahepatic cholestasis in rats. After treatment by XYLDF, 22 biomarkers were reversed to the control-like levels, which involved in primary BA biosynthesis, bile acid metabolism and excretion, steroids metabolism, retinol metabolism, starch and sucrose metabolism, inter conversions between pentose and glucoronate as well as arachidonic acid metabolism. Meanwhile, the results of contents variation of BAs in liver and serum showed that both hydrophilic and hydrophobic BAs were markedly increased in the model rats, while XYLDF treatment could restore the increase induced by ANIT, which suggested that one of the mechanisms of XYLDF on cholestasis referred to regulation of metabolic homeostasis of cholic acid.