Saxifraga umbellulata Attenuates Cholestatic Liver Injury and Modulates Farnesoid X Receptor-Related Bile Acid...

Disrupted bile acid homeostasis represents a central feature of cholestatic liver injury, for which effective therapeutic options remain limited. Saxifraga umbellulata Hook. f. et Thoms. (SU) has traditionally been used in Tibetan medicine to treat hepatobiliary disorders, yet the pharmacological basis of SU remains unclear. Therefore, this study aimed to evaluate the effects of SU on cholestatic liver injury and explore the regulatory mechanisms underlying these effects.

A mouse model of cholestatic liver injury was established by administering α-naphthyl isothiocyanate (ANIT). The effects of SU were evaluated using serum biochemical measurements, liver histopathology, and targeted profiling of hepatic bile acids. Protein expression associated with farnesoid X receptor (FXR) signaling was assessed by Western blotting in liver and ileal tissues. Representative triterpenoids in the SU extract were further examined using molecular docking and HepG2 cell experiments.

SU administration reduced serum markers of hepatocellular injury and cholestasis and lessened hepatic necrosis and inflammatory cell infiltration in ANIT-treated mice. SU also shifted the altered hepatic bile acid profile toward a more balanced state, including partial correction of the disturbed proportions of primary and secondary bile acids. These metabolic changes were accompanied by reduced hepatic CYP7A1 expression and increased expression of BSEP and MRP2. In addition, SU increased ileal FXR and FGF15 expression and hepatic FGFR4 expression, a pattern consistent with coordinated regulation of the intestinal FXR-FGF15/hepatic FGFR4 axis. Meanwhile, molecular docking and HepG2 cell experiments suggested that cucurbitacin IIb and saxifragic acid may contribute to the observed FXR-related responses.

SU mitigated ANIT-induced cholestatic liver injury and promoted partial recovery of hepatic bile acid homeostasis. The protective effects of SU were associated with coordinated changes in hepatic and intestinal FXR-related signaling and with reduced inflammatory injury. These results provide experimental evidence supporting the traditional use of SU for hepatobiliary disorders and highlight cucurbitacin IIb and saxifragic acid as potential bioactive triterpenoids.