Effect of madecassic acid on retinal oxidative stress, inflammation and Growth Factors in streptozotocin-induced diabetic rats

Biochem Biophys Res Commun. 2024 Nov 26:735:150745. doi: 10.1016/j.bbrc.2024.150745. Epub 2024 Sep 25.

Abstract

Diabetic retinopathy (DR) is the leading cause of blindness and visual loss in people with diabetes. It has been suggested that the progression of DR is associated with chronic inflammation and oxidative stress. The aim of the present work was to evaluate the ability of the natural compound madecassic acid (MEA) to reverse the negative impact of streptozotocin (STZ) on retinal injury in rats. Diabetic rats induced by STZ were treated with MEA at the doses of 10 and 20 mg/kg bw for 8 weeks. The study compared the efficacy of the drug in controlling high blood sugar levels and its impact on therapeutic targets such as SOD, CAT, GPx, NF-κB, TNF-α, IL-6, IL-1β, VEGF, IGF, bFGF and Keap1/Nrf-2 pathway. The results showed that the treatment with MEA significantly restored the retinal SOD, CAT, and GPx levels in diabetic rats to the near-normal levels. Moreover, the level of inflammatory mediators (TNF-α, IL-1β, IL-6) and growth factors (VEGF, IGF, bFGF) was significantly lower in retinas of animals treated with MEA as compared to retinas of diabetic animals. The study also established that MEA administration reduced the NF-κB protein and altered the Nrf-2/Keap1 pathway thereby reducing oxidative stress and inflammation. Furthermore, the use of MEA prevented the progression of the retinal capillary basement membrane thickening. It has been found that MEA offers significant protection to the retina and therefore, the compound may be useful in the treatment of DR in humans.

Keywords: Diabetic retinopathy; Growth factors; Inflammation; Madecassic acid; Oxidative stress.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Experimental* / pathology
  • Diabetic Retinopathy* / drug therapy
  • Diabetic Retinopathy* / metabolism
  • Diabetic Retinopathy* / pathology
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Male
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Oxidative Stress* / drug effects
  • Rats
  • Rats, Wistar
  • Retina* / drug effects
  • Retina* / metabolism
  • Retina* / pathology
  • Streptozocin
  • Triterpenes* / pharmacology
  • Triterpenes* / therapeutic use
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Triterpenes
  • madecassic acid
  • Streptozocin
  • Intercellular Signaling Peptides and Proteins
  • NF-E2-Related Factor 2
  • Kelch-Like ECH-Associated Protein 1
  • NF-kappa B
  • KEAP1 protein, rat
  • Nfe2l2 protein, rat
  • Vascular Endothelial Growth Factor A