Analyzing the hepatoprotective effect of the Swertia cincta Burkillextract against ANIT-induced cholestasis in rats by modulating the expression of transporters and metabolic enzymes

Ethnopharmacological relevance: Swertia cincta Burkill was traditionally used for treating jaundice and various types of chronic and acute hepatitis in Yunnan and Tibet in China for hundreds of years. This study aims to investigate the protective effect of S. cincta Burkill (ESC) extract on alpha-naphthylisothiocyanate (ANIT)induced hepatotoxicity and cholestasis in rats. Materials and methods: Crude extracts were prepared using 90% ethanol and by vacuum drying. We utilized an ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of flight tandem mass spectrometry (UHPLC/Q-TOF-MS) system to conduct a phytochemical analysis of the active components of ESC. Liver function was evaluated by measuring the serum levels of enzymes and components and by analyzing the liver histology. We also measured the expression of bile metabolism-related transporters and metabolic enzymes at both protein and mRNA levels to elucidate the underlying mechanisms. Results: ESC analysis using an UHPLC/Q-TOF-MS revealed eight compounds. Oral administration of ESC to ANIT-treated rats can significantly reduce the increases in serum levels of ALT, AST, ALP, TBIL, and TBA. It can also improve liver pathology and bile flow. Western blot and qRT-PCR analyses showed that ESC upregulated the protein and mRNA expression of Fxr, Ntcp, Bsep, Cyp7al, Mrp2, and Mdr2. Conclusion: ESC could alleviate liver injury by reducing enzyme activities of serums, improving liver pathology and bile flow. The protective mechanism was associated with regulation of the expression of hepatic transporters and metabolic enzymes.