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

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 24; pp. 4267 - 4272
• Main Authors: Kuroda, Minpei, Mimaki, Yoshihiro, Sashida, Yutaka, Mae, Tatsumasa, Kishida, Hideyuki, Nishiyama, Tozo, Tsukagawa, Misuzu, Konishi, Eisaku, Takahashi, Kazuma, Kawada, Teruo, Nakagawa, Kaku, Kitahara, Mikio
• Format: Journal Article
• Language: English
• Published: England 15.12.2003
• Subjects: Animals; Binding Sites; Cell Line; Cercopithecus 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
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.09.052

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.