Acteoside delays the fibrosis process of diabetic nephropathy by anti-oxidation and regulating the autophagy-lysosome pathway

Eur J Pharmacol. 2024 Sep 5:978:176715. doi: 10.1016/j.ejphar.2024.176715. Epub 2024 Jun 7.

Abstract

Renal fibrosis is the final pathological change of kidney disease, it has also been recognized to be critical for the final progression of diabetic nephropathy (DN) to kidney failure. Acteoside (ACT) is a phenylethanoid glycoside widely distributed in dicotyledonous plants. It has many pharmacological activities, such as anti-oxidation, anti-inflammation, anti-cancer, neuroprotection, cardiovascular protection, anti-diabetes, bone and cartilage protection, liver and kidney protection, and antibacterial activity. This study aims to investigate the protective effects of ACT on renal interstitial fibrosis in rats with DN induced by intraperitoneal injection of streptozocin (STZ) combined with unilateral nephrectomy and its mechanism. In vivo and in vitro, the effects of ACT on reactive oxygen species (ROS) level, oxidative tubular injury, as well as damage of autophagic flux and lysosome in the DN model were detected. Results indicate that administration of ACT delayed the progression of renal interstitial fibrosis in DN by anti-oxidation and regulating the autophagy-lysosome pathway, which may potentially be attributed to the regulatory influence of ACT on transcription factor EB (TFEB).

Keywords: Acteoside; Autophagy; Diabetic nephropathy; Lysosomes; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants* / pharmacology
  • Autophagy* / drug effects
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies* / drug therapy
  • Diabetic Nephropathies* / metabolism
  • Diabetic Nephropathies* / pathology
  • Fibrosis*
  • Glucosides* / pharmacology
  • Glucosides* / therapeutic use
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Lysosomes* / drug effects
  • Lysosomes* / metabolism
  • Male
  • Oxidative Stress / drug effects
  • Phenols* / pharmacology
  • Phenols* / therapeutic use
  • Polyphenols
  • Rats
  • Rats, Sprague-Dawley*
  • Reactive Oxygen Species* / metabolism
  • Signal Transduction / drug effects

Substances

  • Glucosides
  • Reactive Oxygen Species
  • acteoside
  • Phenols
  • Antioxidants
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TFEB protein, rat
  • Polyphenols