Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
Department of Clinical Pharmacology and Toxicology, Korea University Guro Hospital, Seoul, South Korea.
Metabolomics. 2019 Feb 27;15(3):30. doi: 10.1007/s11306-019-1494-5.
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.
熊去氧胆酸（UDCA）是一种具有肝脏保护作用的肠道细菌代谢物。然而，其作用的分子机制尚不清楚。
本研究旨在通过对健康受试者的全代谢组学分析，探讨 UDCA 治疗作用的机制。
健康韩国男性每天服用 UDCA 剂量为 400、800 或 1200mg，持续 2 周。采集血清样本进行肝功能检查和 miR-122 表达水平测定。使用液相色谱系统与四极杆飞行时间质谱（LC/QTOFMS）和气相色谱-飞行时间质谱（GC/TOFMS）进行尿液和血浆全代谢组学分析。采用无监督多元分析（主成分分析）对治疗前后的鉴别标志物进行分析。
治疗 2 周后，丙氨酸氨基转移酶评分和血清 miR-122 水平显著下降。通过基于 LC 和 GC 的代谢组学分析，我们在血浆和尿液样本中鉴定出 40 种差异代谢物。
肝功能评分的调节和代谢变化突出了 UDCA 的潜在肝脏保护作用，这主要与健康男性的氨基酸、类黄酮和脂肪酸代谢有关。
