The role of pregnane X receptor in hepatic and intestinal diseases: an update

Pregnane X receptor (PXR), a crucial member of the nuclear receptor superfamily, is predominantly expressed in the liver and intestine and serves as a key transcription factor regulating the expression of various drug-metabolizing enzymes and transporters. Beyond its classical role in xenobiotic detoxification, PXR also plays an important role in the metabolism of endogenous substances such as bile acids, lipids, and glucose. In recent years, extensive studies have demonstrated that PXR is closely associated with a variety of hepatic and intestinal diseases, including drug-induced liver injury, metabolic dysfunction-associated fatty liver disease, cholestasis, inflammatory bowel disease, and hepatointestinal malignancies. Multiple PXR agonists—including endogenous ligands, natural products, and synthetic small molecules—have shown significant potential in restoring metabolic homeostasis, regulating inflammation, and maintaining hepatic and intestinal functions. This review highlights the central role of PXR in metabolic regulation, systematically summarizes its mechanisms and recent advances in hepatic and intestinal diseases, and focuses on the development and clinical translation of PXR agonists, aiming to provide a theoretical basis for PXR-targeted therapeutic strategies against liver and intestinal disorders.