Artesunate alleviates diabetic retinopathy by activating autophagy via the regulation of AMPK/SIRT1 pathway

Arch Physiol Biochem. 2023 Dec;129(4):943-950. doi: 10.1080/13813455.2021.1887266. Epub 2021 Mar 4.

Abstract

Context: Artesunate (ART), an antimalarial drug, possesses the ability to induce autophagy and exhibits a protective effect on diabetes.

Objective: This study aimed to evaluate the effects of ART on diabetic retinopathy (DR) and to explore the underlying mechanisms.

Methods: Rats with streptozotocin-induced DR were given intravitreal injection of ART.

Results: ART administration inhibited the increase in retinal thickness and prevented blood-retinal barrier in diabetic rats. Further, vascular leukocyte adherence, microglial activation, inflammatory cytokine, and ROS production in the retinas of diabetic rats were also inhibited by ART. Additionally, ART enhanced autophagy in the retinas of diabetic rats as demonstrated by up-regulated Beclin-1 expression and LC3II/I ratio and down-regulated p62. ART also activated AMP-activated protein kinase (AMPK)/sensor class III histone deacetylase sirtuin 1 (SIRT1) pathway.

Conclusions: ART, as an autophagy activator, has therapeutic potential in DR treatment.

Keywords: AMPK/SIRT1 pathway; Diabetic retinopathy; artesunate; autophagy; inflammation.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Artesunate / pharmacology
  • Autophagy
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetic Retinopathy* / drug therapy
  • Rats
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism

Substances

  • Sirtuin 1
  • AMP-Activated Protein Kinases
  • Artesunate