The inhibitory effect of Isoflavones isolated from Caesalpinia pulcherrima on aldose reductase in STZ induced diabetic rats

Chem Biol Interact. 2015 Jul 25:237:18-24. doi: 10.1016/j.cbi.2015.05.010. Epub 2015 May 15.

Abstract

Increased aldose reductase activity has been implicated in the development of retinopathy due to accumulation of intracellular sugar alcohol, i.e., sorbitol. In this study, the compounds isolated from the Caesalpinia pulcherrima, have been examined for its inhibitory effects on aldose reductase (AR), which plays a major role in diabetic retinopathy. 3,6,7,4',5'-Pentamethoxy-5,3'-dihydroxyflavone (Compound 2) has shown significant inhibition of rat retina AR with an IC50 value of 16.24±0.046μM in a non-competitive manner. Molecular docking study results are steady with the pattern of AR inhibition by Compound 2 and its specificity. The supplementation of Compound 2 suppresses sorbitol accumulation in retina by decreased AR activity in STZ induced diabetic rat in dose dependent manner. Besides this, rats fed with Compound 2 have shown improved levels of antioxidant enzymes. This study revealed that Compound 2 has pharmacologically active component with a potential to inhibit rat retina AR and affecting the delaying process of diabetic retinopathy in STZ induced diabetic rats.

Keywords: Aldose reductase; Aldose reductase inhibitors; Diabetic retinopathy; Enzyme kinetics and molecular docking; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Animals
  • Diabetes Mellitus, Experimental / enzymology*
  • Diabetic Retinopathy / enzymology
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Fabaceae / chemistry*
  • Inhibitory Concentration 50
  • Isoflavones / chemistry
  • Isoflavones / pharmacology*
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Molecular Docking Simulation
  • Rats
  • Retina / enzymology
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Infrared
  • Streptozocin

Substances

  • Enzyme Inhibitors
  • Isoflavones
  • Streptozocin
  • Aldehyde Reductase