Elucidation of inhibitory effects of bioactive anthraquinones towards formation of DNA advanced glycation end products (DNA-AGEs)

Int J Biol Macromol. 2024 Jun;269(Pt 2):131810. doi: 10.1016/j.ijbiomac.2024.131810. Epub 2024 Apr 26.

Abstract

DNA is essential in biological processes as it directs transcription and translation assisting in RNA and protein synthesis. Extended periods of elevated blood glucose levels cause non-enzymatic DNA glycation, which results in the formation of DNA-AGEs and the production of free radicals, causing structural perturbation of DNA. In this work, we have investigated the glycation of calf thymus (ct-DNA) DNA and examined its inhibition by two anthraquinone derivatives, purpurin and aloin. Ribose sugar served as the glycating agent inducing non-enzymatic glycation of DNA and subsequent DNA-AGEs formation. UV-vis and fluorescence spectroscopic methods were utilized to characterize DNA-AGE formation in vitro. Circular dichroism (CD) spectroscopy was used to observe the structural disruption of DNA caused by glycation. The changes in AGEs fluorescence intensity and melting temperature (Tm) were measured to assess the inhibition of glycation process by aloin and purpurin. These derivatives demonstrated inhibitory effects via binding to glycating sites of ct-DNA or by scavenging free radicals generated during glycation. The current study elucidates the inhibitory actions of aloin and purpurin on DNA glycation, suggesting their possible applications in mitigating the adverse consequences linked to increased ribose concentrations.

Keywords: Anthraquinones; DNA glycation; Fluorescence; Inhibition; Molecular docking.

MeSH terms

  • Animals
  • Anthraquinones* / chemistry
  • Anthraquinones* / pharmacology
  • Cattle
  • DNA* / metabolism
  • Emodin / analogs & derivatives
  • Emodin / chemistry
  • Emodin / metabolism
  • Emodin / pharmacology
  • Glycation End Products, Advanced* / metabolism
  • Glycosylation / drug effects
  • Spectrometry, Fluorescence

Substances

  • Glycation End Products, Advanced
  • Anthraquinones
  • DNA
  • calf thymus DNA
  • Emodin
  • purpurin anthraquinone
  • alloin