Glaucine inhibits hypoxia-induced angiogenesis and attenuates LPS-induced inflammation in human retinal pigment epithelial ARPE-19 cells

Eur J Pharmacol. 2024 Oct 15:981:176883. doi: 10.1016/j.ejphar.2024.176883. Epub 2024 Aug 10.

Abstract

Glaucine is an aporphine alkaloid with anti-inflammatory, bronchodilator and anti-cancer activities. However, the effects of glaucine in the regulation of age-related macular degeneration (AMD) remain unclear. Herein, we aimed to investigate the anti-angiogenetic and anti-inflammatory effects of glaucine in ARPE-19 cells. ARPE-19 cells were treated with N-(methoxyoxoacetyl)-glycine, methyl ester (DMOG) and cobalt chloride (CoCl2) for induction of hypoxia, while lipopolysaccharide (LPS) treatment was used for elicitation of inflammatory response. Cell viability was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The expression of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by Western blot. The secretion of VEGF, interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) was detected using enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were used for tube formation analysis. Expression of HIF-1α and secretion of VEGF were significantly increased under DMOG and CoCl2 induction, whereas glaucine significantly attenuated both HIF-1α expression and VEGF secretion by DMOG- and CoCl2-induced ARPE-19 cells. In addition, glaucine suppressed the tube formation by DMOG- and CoCl2-induced HUVEC cells. Moreover, glaucine also attenuated the production of IL-6 and MCP-1 by LPS-induced ARPE-19 cells. This study indicated that glaucine exhibited anti-angiogenic and anti-inflammatory effects, suggesting that glaucine might have benefits for the treatment of AMD.

Keywords: AMD; Angiogenesis; HIF-1α; Hypoxia; IL-6; Inflammation; MCP-1; VEGF.

MeSH terms

  • Angiogenesis
  • Angiogenesis Inhibitors / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Aporphines* / pharmacology
  • Cell Hypoxia / drug effects
  • Cell Line
  • Cell Survival* / drug effects
  • Chemokine CCL2 / metabolism
  • Cobalt / pharmacology
  • Cobalt / toxicity
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / pathology
  • Lipopolysaccharides*
  • Neovascularization, Pathologic / drug therapy
  • Retinal Pigment Epithelium* / cytology
  • Retinal Pigment Epithelium* / drug effects
  • Retinal Pigment Epithelium* / metabolism
  • Retinal Pigment Epithelium* / pathology
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Lipopolysaccharides
  • Vascular Endothelial Growth Factor A
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Aporphines
  • Anti-Inflammatory Agents
  • Angiogenesis Inhibitors
  • HIF1A protein, human
  • Cobalt
  • cobaltous chloride
  • Chemokine CCL2