Isoliquiritigenin downregulates miR-195 and attenuates oxidative stress and inflammation in STZ-induced retinal injury

Naunyn Schmiedebergs Arch Pharmacol. 2020 Dec;393(12):2375-2385. doi: 10.1007/s00210-020-01948-5. Epub 2020 Jul 22.

Abstract

Diabetic retinopathy (DR) is a major microvascular complication of diabetes mellitus that leads to significant vision loss. Isoliquiritigenin (ISL) is a bioactive flavonoid found in the root of licorice with reported anti-oxidant and anti-inflammatory activities. In the present study, we evaluated the effect of ISL administration on diabetes-induced retinal injury. Diabetes was induced in male Sprague-Dawley rats using single intraperitoneal streptozotocin (STZ, 50 mg/kg) injection. Diabetic rats showed up-regulated retinal miR-195, reduced retinal levels of SIRT-1, and increased levels of oxidative stress, nuclear factor-κB (NF-κB), inflammatory cytokines, and endothelin-1. Moreover, histopathological and electron microscopy studies revealed distorted retinal layers and reduced number of ganglion cells. Oral administration of ISL (20 mg/kg/day) to diabetic rats for 8 weeks improved diabetes-induced retinal injury via down-regulation of miR-195, restoration of retinal SIRT-1 level, attenuation of oxidative stress, inflammation, and endothelial damage as well as preservation of retinal normal histology and ultrastructure. In conclusion, our results showed that ISL could be a promising therapeutic intervention to prevent the development and progression of DR. It also suggested that the miR-195/SIRT-1/NF-κB pathway may contribute to ISL treatment-induced beneficial effects.

Keywords: Isoliquiritigenin; NF-κB; SIRT-1; miR-195.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Chalcones / pharmacology
  • Chalcones / therapeutic use*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Retinopathy / chemically induced
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / metabolism
  • Down-Regulation / drug effects*
  • Down-Regulation / physiology
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism
  • Male
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin / toxicity

Substances

  • Chalcones
  • Inflammation Mediators
  • MIRN195 microRNA, rat
  • MicroRNAs
  • Streptozocin
  • isoliquiritigenin