Triptolide Suppresses Alkali Burn-Induced Corneal Angiogenesis Along with a Downregulation of VEGFA and VEGFC Expression

Anat Rec (Hoboken). 2017 Jul;300(7):1348-1355. doi: 10.1002/ar.23583. Epub 2017 Mar 14.


Triptolide (TPL) is an active compound extracted from a Chinese herbal medicine tripterygium wilfordii Hook. f. (Celastraceae), which has been used as an anti-inflammatory drug for years. It also inhibits the growth and proliferation of different types of cancer cells. The inhibitory effect of TPL on angiogenesis after chemical-induced corneal inflammation was studied in vivo. The effects of TPL on the proliferation, apoptosis, migration, and tube formation of rat aortic endothelial cells (RAECs) were studied in vitro. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. Migration was analyzed using the scratch wound healing assay and transwell assay. Tube formation assay was used to examine angiogenesis. Real-time PCR and Western blot were used to determine the expression of vascular endothelial growth factor A (VEGFA) and VEGFC. To study the in vivo effects of TPL, the mouse model of alkali burn-induced corneal angiogenesis was used. The angiogenesis was analyzed by determining the density of the newly generated blood vessels in corneas. We found that TPL induced apoptosis and inhibited the proliferation of RAECs in a dose-dependent manner. TPL inhibited migration and tube formation of RAECs and decreased the expression of VEGFA and VEGFC in vitro. Furthermore, TPL suppressed alkali burn-induced corneal angiogenesis and inhibited the expression of VEGFA and VEGFC in corneas in vivo. In conclusion, topical TPL as a pharmacological agent has the ability to reduce angiogenesis in cornea and may have clinical indications for the treatment of corneal angiogenesis diseases which have to be further explored. Anat Rec, 300:1348-1355, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: angiogenesis; cornea; triptolide; vascular endothelial growth factor.

MeSH terms

  • Alkalies / toxicity*
  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Corneal Neovascularization / chemically induced
  • Corneal Neovascularization / metabolism
  • Corneal Neovascularization / prevention & control*
  • Diterpenes / pharmacology*
  • Epoxy Compounds / pharmacology
  • Eye Burns / chemically induced
  • Eye Burns / metabolism
  • Eye Burns / prevention & control*
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / chemically induced
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / prevention & control*
  • Phenanthrenes / pharmacology*
  • Rats
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor C / metabolism*


  • Alkalies
  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • triptolide