Novel findings of 18β-glycyrrhetinic acid on sRAGE secretion through inhibition of transient receptor potential canonical channels in high-glucose environment

Zih-Ying Li, Yu-Tang Tung, Sheng-Yi Chen, Gow-Chin Yen

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Enhancing soluble receptor for advanced glycation endproducts (sRAGE) is considered as a potent strategy for diabetes therapy. sRAGE secretion is regulated by calcium and transient receptor potential canonical (TRPC) channels. However, the role of TRPC channels in diabetes remains unknown. 18β-Glycyrrhetinic acid (18β-GA), produced from liquorice, has shown antidiabetic properties. This study was aimed to investigate the effect of 18β-GA on sRAGE secretion via TRPC channels in high glucose (HG)-induced THP-1 cells. HG treatment enhanced TRPC3 and TRPC6 expression and consequently caused reactive oxygen species (ROS) accumulation mediated through p47 nicotinamide-adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) associated with uncoupling protein 2 (UCP2) decline and lower sRAGE secretion. Interestingly, 18β-GA showed the dramatic effects similar to Pyr3 or 2-aminoethyl diphenyl borinate inhibitors and effectively reversed HG-elicited mechanisms including that blocking TRPC3 and TRPC6 protein expressions, suppressing intracellular [Ca2+] concentration, decreasing expressions of ROS, p47s, and iNOS, but increasing UCP2 level and promoting sRAGE secretion. Therefore, 18β-GA provides a potential implication to diabetes mellitus and its complications.

Original languageEnglish
Pages (from-to)607-615
Number of pages9
JournalBioFactors
Volume45
Issue number4
Early online dateMay 23 2019
DOIs
Publication statusPublished - 2019

Keywords

  • 18β-glycyrrhetinic acid
  • THP-1
  • TRPC
  • high glucose
  • sRAGE

ASJC Scopus subject areas

  • Molecular Medicine
  • Biochemistry
  • Clinical Biochemistry

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