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Simultaneously screening multiple UGT1A1 inhibitors from Polygonum multiflorum root using ultrafiltration LC-MS.

Yan Jiang1, Cai Zhang2, Xian Zheng2

  • 1College of Chemical Engineering, Nanjing Forestry University, Nanjing, China.

Biomedical Chromatography : BMC
|December 18, 2021
PubMed
Summary

Polygonum multiflorum root (PMR) can cause liver injury. This study identified UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors in PMR that contribute to this hepatotoxicity, confirmed in zebrafish and mice.

Keywords:
hepatotoxicity, Polygonum multiflorum root, UDP-glucuronosyltransferase 1A1 inhibitor, ultrafiltration, zebrafish

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Area of Science:

  • Pharmacology
  • Hepatotoxicity
  • Natural Products

Background:

  • Polygonum multiflorum root (PMR) is associated with liver injury.
  • UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors are implicated in PMR-induced hepatotoxicity.

Purpose of the Study:

  • To screen for UGT1A1 inhibitors within PMR.
  • To determine the contribution of these inhibitors to PMR-induced liver injury.

Main Methods:

  • Ultrafiltration coupled with Liquid Chromatography-Mass Spectrometry (LC-MS) for compound screening.
  • In vitro enzyme inhibition assays (IC50 determination).
  • Molecular docking simulations and in vivo assays (zebrafish larvae and mice).

Main Results:

  • Four compounds were identified as UGT1A1 inhibitors: cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-glucoside, trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside, emodin-8-O-β-d-glucoside, and emodin.
  • In vitro inhibitory activities (IC50 values) ranged from 18.70 to 76.23 μM.
  • In vivo studies confirmed that these UGT1A1 inhibitors contribute to PMR-induced hepatotoxicity.

Conclusions:

  • UGT1A1 inhibitors are present in PMR.
  • These inhibitors play a role in the liver injury caused by PMR.
  • Findings enhance understanding of PMR hepatotoxicity mechanisms.