Cucurbita argyrosperma Seed Extracts Attenuate Angiogenesis in a Corneal Chemical Burn Model

Nutrients. 2019 May 27;11(5):1184. doi: 10.3390/nu11051184.

Abstract

Severe corneal inflammation produces opacity or even perforation, scarring, and angiogenesis, resulting in blindness. In this study, we used the cornea to examine the effect of new anti-angiogenic chemopreventive agents. We researched the anti-angiogenic effect of two extracts, methanol (Met) and hexane (Hex), from the seed of Cucurbita argyrosperma, on inflamed corneas. The corneas of Wistar rats were alkali-injured and treated intragastrically for seven successive days. We evaluated: opacity score, corneal neovascularization (CNV) area, re-epithelialization percentage, and histological changes. Also, we assessed the inflammatory (cyclooxigenase-2, nuclear factor-kappaB, and interleukin-1β) and angiogenic (vascular endothelial growth factor A, VEGF-A; -receptor 1, VEGFR1; and -receptor 2, VEGFR2) markers. Levels of Cox-2, Il-1β, and Vegf-a mRNA were also determined. After treatment, we observed a reduction in corneal edema, with lower opacity scores and cell infiltration compared to untreated rats. Treatment also accelerated wound healing and decreased the CNV area. The staining of inflammatory and angiogenic factors was significantly decreased and related to a down-expression of Cox-2, Il-1β, and Vegf. These results suggest that intake of C. argyrosperma seed has the potential to attenuate the angiogenesis secondary to inflammation in corneal chemical damage.

Keywords: Cucurbita argyrosperma; angiogenesis; corneal chemical burn; corneal neovascularization (CNV); cyclooxigenase-2 (COX-2); interleukin-1β (IL-1β); nuclear factor-kappaB (NF-κB); vascular endothelial growth factor (VEGF).

MeSH terms

  • Angiogenesis Inhibitors / isolation & purification
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenic Proteins / metabolism
  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Burns, Chemical / drug therapy*
  • Burns, Chemical / metabolism
  • Burns, Chemical / pathology
  • Cornea / blood supply*
  • Cornea / drug effects*
  • Cornea / metabolism
  • Corneal Neovascularization / drug therapy*
  • Corneal Neovascularization / metabolism
  • Corneal Neovascularization / pathology
  • Corneal Opacity / drug therapy
  • Corneal Opacity / metabolism
  • Corneal Opacity / pathology
  • Cucurbita* / chemistry
  • Disease Models, Animal
  • Eye Burns / drug therapy*
  • Eye Burns / metabolism
  • Eye Burns / pathology
  • Inflammation Mediators / metabolism
  • Male
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Rats, Wistar
  • Seeds* / chemistry
  • Signal Transduction / drug effects
  • Wound Healing / drug effects

Substances

  • Angiogenesis Inhibitors
  • Angiogenic Proteins
  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Plant Extracts