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.
KeywordsUrsodeoxycholic acid Global metabolomics Hepatoprotective effect Amino acid Flavonoid Fatty acid
DJK was responsible for experimental set up, measurements and analysis of data, interpretation of data, and manuscript writing. SCJ performed miR-122 measurements. HC, SHL, KSY, and IJJ helped with clinical study design, interpretation of data, and edited the manuscript. JYC contributed to the experimental design and manuscript editing. All authors participated sufficiently in the presented work and approved the final version of the manuscript.
This study was supported in part by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant No.: HI14C2770).
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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