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

Sharifa Alzahrani, Sadeem M. Ajwah, Sumayyah Yasser Alsharif, Eman Said, Mohamed El-Sherbiny, Sawsan A. Zaitone, Mohamed Al-Shabrawey, Nehal M. Elsherbiny

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2375-2385
Number of pages11
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume393
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • Isoliquiritigenin
  • NF-κB
  • SIRT-1
  • miR-195

ASJC Scopus subject areas

  • Pharmacology

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