Corosolic acid: antiangiogenic activity and safety of intravitreal injection in rats eyes

Doc Ophthalmol. 2019 Jun;138(3):181-194. doi: 10.1007/s10633-019-09682-x. Epub 2019 Feb 26.

Abstract

Purpose: Investigate the potential application of corosolic acid (CA) in the treatment of diseases causing retinal neovascularization.

Methods: CA cytotoxicity effect was evaluated in ARPE-19 cells by sulforhodamine B colorimetric method, and antiangiogenic activity was studied using chorioallantoic membrane (CAM) assay. An amount of 0.01 mL of CA formulations at 5, 10 and 25 µM was injected in the right eyes of Wistar rats, and the contralateral eyes received the vehicle to verify the safety of ophthalmic use. Electroretinography (ERG) was performed before, 7 and 15 days after CA administration. Animals were killed on the 15th day, and the histological analysis of retina was carried out under light microscopy.

Results: CA did not present cytotoxicity at concentrations below 35.5 μM after 48 h of treatment. The antiangiogenic activity was confirmed by CAM assay, since CA (range from 5 to 25 µM) induced a significant reduction in vascularity without any signs of toxicity. ERG recordings and histological evaluation did not show any signs of retinal toxicity.

Conclusions: CA was effective in reducing vascularity in a CAM model and was found to be safe for potential ophthalmic use.

Keywords: Antiangiogenic; Corosolic acid; Neovascularization process; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / toxicity
  • Animals
  • Cell Line
  • Chorioallantoic Membrane / blood supply
  • Electroretinography / drug effects
  • Intravitreal Injections
  • Male
  • Neovascularization, Pathologic / drug therapy
  • Rats
  • Rats, Wistar
  • Retina / drug effects*
  • Retinal Pigment Epithelium / drug effects
  • Triterpenes / administration & dosage*
  • Triterpenes / toxicity
  • Vitreous Body / drug effects

Substances

  • Angiogenesis Inhibitors
  • Triterpenes
  • corosolic acid