Abstract

HARNESSING FARNESOID X RECEPTOR (FXR) ACTIVATION FOR LIVER PROTECTION: INSIGHTS FROM SYNTHETIC COMPOUNDS AND PLANT-DERIVED LIGANDS

Shafin M. Paneri and Nayeem A. Khatib*

Abstract

This review critically explores the therapeutic potential of both synthetic and phytochemical-based Farnesoid X Receptor (FXR) agonists in managing drug-induced liver injury (DILI) and cholestatic liver diseases. It compiles evidence from preclinical and clinical studies on synthetic agents such as obeticholic acid, tropifexor, cilofexor, INT-767, and fluorofenidone, alongside plant-derived modulators including Papaverine, 7,8-dihydroxy-4-methyl coumarin (DMC), Sarmentol H, Gardenia jasminoides extract, and Saffron constituents. These agents act through modulation of bile acid metabolism, FXR activation, and attenuation of inflammation and fibrosis. While synthetic FXR agonists are effective, they are often limited by adverse effects such as pruritus and dyslipidaemia. Conversely, phytochemical modulators offer anti-inflammatory, antioxidative, and hepatoprotective benefits, though concerns such as paradoxical hepatotoxicity, evident with Epimedii folium, highlight the need for cautious validation. Collectively, these insights support the growing potential of phytochemicals as viable FXR-targeted interventions, while emphasizing the importance of rigorous pharmacological profiling and clinical validation to ensure safe and effective therapeutic use.

Keywords: Farnesoid X Receptor (FXR), Cholestasis, DILI, Synthetic FXR agonist, Phytochemical FXR modulators, Hepatoprotection.