Natural bioactive compounds reprogram bile acid metabolism in MAFLD: Multi-target mechanisms and therapeutic implications

Metabolic-associated fatty liver disease (MAFLD) has become an increasingly prevalent liver disorder worldwide, being closely associated with obesity, metabolic syndrome, and insulin resistance. Bile acids (BAs), beyond their traditional role in lipid digestion, play a pivotal part in regulating lipid and glucose metabolism as well as inflammatory responses. Recent investigations have recognized BAs as key factors in the onset and progression of MAFLD, mainly via their interactions with nuclear receptors such as the farnesoid X receptor (FXR) and the G protein-coupled bile acid receptor (TGR5). Additionally, active compounds derived from traditional Chinese medicine (TCM) have shown promising potential in the treatment of MAFLD. This study systematically reviews and analyzes the molecular mechanisms and recent progress in the application of TCM active ingredients for MAFLD treatment, with a focus on their regulation of BAs. These active ingredients, including saponins, flavonoids, polysaccharides, and sterols, exert therapeutic effects through diverse mechanisms, such as modulating BA synthesis and mediating receptor-signaling pathways, and are expected to restore metabolic homeostasis.