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Metabolomics

, 15:30 | Cite as

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

  • Da Jung Kim
  • Hyewon Chung
  • Sang Chun Ji
  • SeungHwan Lee
  • Kyung-Sang Yu
  • In-Jin Jang
  • Joo-Youn ChoEmail author
Original Article

Abstract

Introduction

Ursodeoxycholic acid (UDCA) is an intestinal bacterial metabolite with hepatoprotective effects. However, molecular mechanisms underlying its effects remain unclear.

Objectives

The aim of this study was to investigate the mechanisms underlying the therapeutic effects of UDCA by using global metabolomics analyses in healthy subjects.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Ursodeoxycholic acid Global metabolomics Hepatoprotective effect Amino acid Flavonoid Fatty acid 

Notes

Author contributions

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.

Funding

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.

Ethical approval

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.

Supplementary material

11306_2019_1494_MOESM1_ESM.docx (147 kb)
Supplementary material 1 (DOCX 146 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Da Jung Kim
    • 1
  • Hyewon Chung
    • 1
    • 2
  • Sang Chun Ji
    • 1
  • SeungHwan Lee
    • 1
  • Kyung-Sang Yu
    • 1
  • In-Jin Jang
    • 1
  • Joo-Youn Cho
    • 1
    Email author
  1. 1.Department of Clinical Pharmacology and TherapeuticsSeoul National University College of Medicine and HospitalSeoulSouth Korea
  2. 2.Department of Clinical Pharmacology and ToxicologyKorea University Guro HospitalSeoulSouth Korea

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