Phenolics with PPAR-gamma ligand-binding activity obtained from licorice (Glycyrrhiza uralensis roots) and ameliorative effects of glycyrin on genetically diabetic KK-A(y) mice

Bioorg Med Chem Lett. 2003 Dec 15;13(24):4267-72. doi: 10.1016/j.bmcl.2003.09.052.

Abstract

The EtOAc extract of licorice (Glycyrrhiza uralensis roots) exhibited considerable PPAR-gamma ligand-binding activity. Bioassay-guided fractionation of the extract using a GAL-4-PPAR-gamma chimera assay method resulted in the isolation of two isoflavenes, one of which is a new compound named dehydroglyasperin D, an isoflavan, two 3-arylcoumarins, and an isoflavanone as the PPAR-gamma ligand-binding active ingredients of licorice. The isoprenyl group at C-6 and the C-2' hydroxyl group in the aromatic ring-C part in the isoflavan, isoflavene, or arylcoumarin skeleton were found to be the structural requirements for PPAR-gamma ligand-binding activity. Glycyrin, one of the main PPAR-gamma ligands of licorice, significantly decreased the blood glucose levels of genetically diabetic KK-A(y) mice.

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • Chlorocebus aethiops
  • Coumarins / therapeutic use*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Glycyrrhiza*
  • Hypoglycemic Agents / therapeutic use*
  • Ligands
  • Mice
  • Mice, Mutant Strains
  • Phenols / pharmacokinetics
  • Phenols / pharmacology*
  • Phenols / therapeutic use
  • Phytotherapy*
  • Pioglitazone
  • Plant Extracts / pharmacokinetics
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Structure-Activity Relationship
  • Thiazolidinediones / therapeutic use
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Coumarins
  • Hypoglycemic Agents
  • Ligands
  • Phenols
  • Plant Extracts
  • Receptors, Cytoplasmic and Nuclear
  • Recombinant Fusion Proteins
  • Thiazolidinediones
  • Transcription Factors
  • Pioglitazone