Mechanism of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) transactivation by hesperetin glucuronides is distinct from that by a thiazolidine-2,4-dione agent

Kanae Gamo, Takuma Shiraki, Nobuyasu Matsuura, Hiroyuki Miyachi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Hesperidin, a flavanone glycoside present abundantly in citrus fruits, is predominantly metabolized to hesperetin-7-O-β-D-glucuronide (H7-OG) and hesperetin-3′-O-β-D-glucuronide (H′-OG), which exhibit partial agonistic activity towards peroxisome proliferator-activated receptor gamma (PPARγ). Here, in order to understand the mechanism(s) of action of PPARγ transactivation elicited by hesperetin glucuronides, we compared the transactivation activities of PPARγ (ligand-binding domain (LBD)) mutants by hesperetin glucuronides and troglitazone, a thiazolidine-2,4-dione class PPARγ full agonist. The assay results indicated that the mechanisms of activation of PPARγ by hesperetin glucuronides and by troglitazone are distinct, probably due to a difference in the binding sites of these compounds on the PPARγ LBD. Flavanone-class PPARγ partial agonists, luteolin and hesperetin glucuronides, showed similar activation profiles of the PPARγ LBD mutants, even though they have different side chain functionalities.

Original languageEnglish
Pages (from-to)491-493
Number of pages3
JournalChemical and Pharmaceutical Bulletin
Volume62
Issue number5
DOIs
Publication statusPublished - May 2014

Keywords

  • Hesperetin
  • Hesperetin glucuronide
  • Hesperidin
  • PPARγ mutant
  • Peroxisome proliferator-activated receptor gamma (PPARγ)

ASJC Scopus subject areas

  • Chemistry(all)
  • Drug Discovery

Fingerprint Dive into the research topics of 'Mechanism of Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) transactivation by hesperetin glucuronides is distinct from that by a thiazolidine-2,4-dione agent'. Together they form a unique fingerprint.

  • Cite this