Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways

Ursodeoxycholic acid (UDCA) is an intestinal bacterial metabolite with hepatoprotective effects. However, molecular mechanisms underlying its effects remain unclear. The aim of this study was to investigate the mechanisms underlying the therapeutic effects of UDCA by using global metabolomics analyses in healthy subjects. Healthy Korean men were administered UDCA at dosage of 400, 800, or 1200 mg daily for 2 weeks. Serum samples were collected and used for liver function tests and to determine miR-122 expression levels. Urinary and plasma global metabolomics analyses were conducted using a liquid chromatography system coupled with quadrupole-time-of-flight mass spectrometry (LC/QTOFMS) and gas chromatography-TOFMS (GC/TOFMS). Unsupervised multivariate analysis (principal component analysis) was performed to identify discriminative markers before and after treatment. Alanine transaminase score and serum miR-122 levels decreased significantly after 2 weeks of treatment. Through LC- and GC-based metabolomic profiling, we identified 40 differential metabolites in plasma and urine samples. Regulation of liver function scores and metabolic alternations highlight the potential hepatoprotective action of UDCA, which were primarily associated with amino acid, flavonoid, and fatty acid metabolism in healthy men.