Isoliquiritigenin attenuates inflammation and modulates Nrf2/caspase-3 signalling in STZ-induced aortic injury

J Pharm Pharmacol. 2021 Mar 4;73(2):193-205. doi: 10.1093/jpp/rgaa056.

Abstract

Objectives: The current study provides evidence on the ameliorative impact of Isoliquiritigenin (ISL), a natural bioflavonoid isolated from licorice roots against diabetes mellitus (DM)-induced aortic injury in rats.

Methods: DM was induced in male Sprague-Dawley rats by single I.P. injection of STZ (50 mg/kg). ISL was administrated daily (20 mg/kg, orally) for 8 wks.

Key findings: Diabetic group showed a significant aortic injury with evidence of atherosclerotic lesions development. Daily ISL (20 mg/kg, orally) administration for 8 wks significantly restored aortic oxidative/antioxidative stress homeostasis via modulating NrF-2/Keap-1/HO-1. Moreover, ISL treatment restored aortic levels of IL-10 and dampened aortic levels of IL-6 and TNF-α. Caspase-3 expression significantly declined as well. Further, ISL treatment successfully suppressed aortic endothelin-1 (ET-1) expression and restored NO contents, eNOS immunostaining paralleled with retraction in atherosclerotic lesions development, and lipid deposition with histopathological architectural preservation and restoration of almost normal aortic thickness.

Conclusion: ISL can be proposed to be an effective protective therapy to prevent progression of DM-induced vascular injury and to preserve aortic integrity.

Keywords: Aorta; Caspase-3; Diabetes Mellitus; Endothelin-1; Isoliquiritigenin; NrF2.

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Aorta / pathology
  • Caspase 3 / metabolism
  • Chalcones / isolation & purification
  • Chalcones / pharmacology*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / pathology
  • Disease Progression
  • Glycyrrhiza / chemistry
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Male
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Rats
  • Signal Transduction / drug effects
  • Streptozocin

Substances

  • Chalcones
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Streptozocin
  • isoliquiritigenin
  • Casp3 protein, rat
  • Caspase 3