Nrf2 activators from Glycyrrhiza inflata and their hepatoprotective activities against CCl4-induced liver injury in mice

Bioorg Med Chem. 2017 Oct 15;25(20):5522-5530. doi: 10.1016/j.bmc.2017.08.018. Epub 2017 Aug 15.

Abstract

Glycyrrhiza inflata (licorice) has been used to treat liver diseases for a long history. However, the bioactive compounds are still not clear. In this work, 77 compounds, including 9 new ones, were isolated from the EtOAc extract of the roots and rhizomes of G. inflata. The Nrf2 activation activities of all compounds were screened using ARE-luciferase reporter assay on HepG2C8 cells. The results indicated a number of chalcones were potent Nrf2 activators, including 11 (licochalcone A, 4.07-fold), 12 (licochalcone B, 5.17-fold), and 19 (echinatin, 4.09-fold). Further studies indicated that 11, 12 and 19 remarkably attenuated CCl4-induced acute liver injury in mice (10 or 50mg/kg, 7days, ig.). These compounds could be promising hepatoprotective natural agents.

Keywords: CCl(4)-induced liver injury; Chalcones; Glycyrrhiza inflata; Hepatoprotective; Nrf2 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Carbon Tetrachloride
  • Cell Survival / drug effects
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glycyrrhiza / chemistry*
  • Hep G2 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred ICR
  • Molecular Structure
  • NF-E2-Related Factor 2 / metabolism*
  • Plant Extracts / administration & dosage
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Roots / chemistry
  • Rats
  • Rats, Sprague-Dawley

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Plant Extracts
  • Carbon Tetrachloride