Dataset for: Rhein targets the farnesoid X receptor to resolve acute intrahepatic cholestasis via gut microbial bile acid biotransformation and hepatic glutamate metabolism recovery

Cholestatic liver injury is a severe metabolic disorder characterized by the toxic accumulation of bile acids (BAs). Rhein is a natural bioactive anthraquinone with potent hepatoprotective properties. However, its specific molecular targets and systemic mechanisms remain unclear. This study investigated the protective effects of rhein against acute intrahepatic cholestasis in an alpha-naphthylisothiocyanate (ANIT)-induced mouse model. Mechanistically, rhein directly targets the farnesoid X receptor (FXR) within the enterohepatic system. Receptor activation suppresses the primary biosynthetic enzyme CYP7A1 and upregulates canalicular efflux transporters. This effectively clears hepatotoxic conjugated BAs, including taurocholic acid and taurochenodeoxycholic acid. Furthermore, rhein triggers comprehensive hepatic metabolic recovery. It prevents the depletion of the intracellular L-glutamate pool, thereby sustaining the urea cycle for nitrogen balance and promoting proline synthesis for tissue repair. Concurrently, rhein selectively remodels the gut microbiota by suppressing the pathogenic expansion of Escherichia-Shigella while enriching functional taxa, specifically Lactobacillus and Colidextribacter. These microbial shifts accelerate BA deconjugation and the formation of secondary BAs, such as deoxycholic acid. These integrated actions enhance fecal BA excretion and restore enterohepatic homeostasis. Overall, these findings highlight rhein as a promising functional food component that coordinates the gut–liver axis, offering a potent dietary intervention strategy for the management of cholestatic disorders.