Characterization of DHDP, a novel aldose reductase inhibitor isolated from Lysimachia christinae

Abstract

The aldose reductase (AR) inhibitory effect of Lysimachia christinae was investigated as a functional food ingredient and a new AR inhibitor, DHDP, was isolated from L. christinae, guided by an affinity-based ultrafiltration-HPLC assay. The chemical structure of DHDP was determined to be 1,5-di-hydroxy-1,5-di-[(E)-3-(4-hydroxyphenyl)-2-propenoic]-3-pentanonyl ester by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), fast atom bombardment ionization mass spectrometry (FAB-MS), and ultraviolet (UV) and (IR) infrared spectroscopy. In addition, the AR inhibitory activity and mechanism of DHDP were characterized. In vitro and in silico results demonstrated that DHDP binds to the AR active site rapidly, blocking it and competitively preventing substrate access and product formation (IC50, 194.67 μM; Ki, 29.68 μM). Ex vivo experiments indicated that DHDP can penetrate the eye lens and successfully inhibit AR under hyperglycemic conditions, thus preventing the accumulation of sorbitol and subsequent osmotic stress.

Keywords

• Aldose reductase
• Lysimachia christinae
• Ultrafiltration
• 1,5-Di-hydroxy-1,5-di-[(E)-3-(4-hydroxyphenyl)-2-propenoic]-3-pentanonyl ester