Luteolin Attenuates Diabetic Nephropathy through Suppressing Inflammatory Response and Oxidative Stress by Inhibiting STAT3 Pathway

Exp Clin Endocrinol Diabetes. 2021 Oct;129(10):729-739. doi: 10.1055/a-0998-7985. Epub 2020 Jan 2.

Abstract

Background: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). DN has many pathological changes, but tubular injury is considered to be a crucial pathological feature and plays a key role in the progression of DN. Accumulating studies have confirmed that Luteolin (3,4,5,7-tetrahydroxyflavone, Lut) possesses anti-inflammatory and antioxidant activities, which may play a role in kidney protection in DN.

Objectives: This paper described the effects of Lut on appropriated tubular injury in the kidneys of db/db mice and searched the possible mechanisms underlying the kidney protection effect in DN.

Methods: Twelve-week-old male C57BL/6 J db/db and C57BL/6 J db/m mice were used for the animal experiments. They were organized into the following five groups for the animal experiments: a db/m group (control, n=6); a db/db group(n=8) ; a db/db group receiving Lut (10 mg/kg/day, n=8)treatment by oral gavage; a db/db group receiving stattic (a selective STAT3 inhibitor,50 mg/Kg/day, n=8) treatment by oral gavage and a db/db group receiving both stattic and Lut treatment by oral gavage.

Results: In this study, we found that Lut might ameliorate glomerular sclerosis and interstitial fibrosis in DN mouse models through inhibiting the inflammatory response and oxidative stress. And it might play its biological function mainly through repressing the STAT3 activation.

Conclusions: Lut attenuates DN mainly via suppression of inflammatory response and oxidative response. STAT3 pathway is the potential target, which ultimately reduces renal fibrosis and delays the progress of DN.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Cyclic S-Oxides / administration & dosage
  • Cyclic S-Oxides / pharmacology*
  • Diabetic Nephropathies / drug therapy*
  • Disease Models, Animal
  • Luteolin / administration & dosage
  • Luteolin / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cyclic S-Oxides
  • STAT3 Transcription Factor
  • stattic
  • Luteolin