Amarogentin relieves cholestatic liver injury caused by ANIT in rats by regulating the FXR and Nrf2 pathways

Articles in Press

Document Type : Original Article

Authors

1 Chongqing Three Gorges Medical College, Chongqing 404120, China

2 Chongqing Key Laboratory of Development and Utilization of Genuine Medicinal Materials in Three Gorges Reservoir Area, Chongqing 404120, China

3 Chongqing Medical and Pharmaceutical College, Chongqing 401331, China

10.22038/ijbms.2025.87063.18815

Abstract

Objective(s): Cholestasis, a hepatic disorder characterized by impaired bile secretion, drives progressive liver damage, fibrosis, failure, and even death. This study explores how amarogentin (AG) ameliorates cholestatic liver injury in rats induced by α-naphthylisothiocyanate (ANIT).
Materials and Methods: The bile flow rate, a visual indicator of the degree of intrahepatic cholestasis, was measured to assess the model’s success. Liver function was evaluated by analyzing the serum levels of enzymes (ALP, ALT, AST, TBIL, DBIL, and TBA), as well as indicators of oxidative damage (SOD, MDA, and GSH-Px), in the liver tissue, and by examining liver histopathology. Additionally, Western blot analysis was utilized to assess the protein levels of the FXR and Nrf2 signaling pathways in the liver tissue of cholestatic rats both before and after AG treatment, to understand the underlying protective mechanism.
Results: AG was administered intragastrically to ANIT-treated cholestatic rats, which significantly decreased the plasma concentrations of AST, ALT, ALP, TBIL, DBIL, and TBA, and alleviated ANIT-induced liver injury. AG could also significantly improve the bile flow rate and suppress oxidative stress. Western blot analysis revealed that AG could enhance ANIT-induced cholestasis by modulating the anti-oxidative system via activation of the PI3K/Akt/Nrf2 pathway and by regulating bile acid metabolism.
Conclusion: This study demonstrated that AG may mitigate ANIT-induced cholestatic liver damage by improving the bile flow rates, decreasing the concentrations of liver function markers and serum enzyme levels, enhancing liver histology, activating Nrf2 via the PI3K/Akt signaling pathway, and controlling bile acid transport.

Graphical Abstract

Amarogentin relieves cholestatic liver injury caused by ANIT in rats by regulating the FXR and Nrf2 pathways

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 29 October 2025

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