Antifibrotic Effects of Sakuraso-Saponin in Primary Cultured Pterygium Fibroblasts in Comparison With Mitomycin C

Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4784-4791. doi: 10.1167/iovs.19-27153.

Abstract

Purpose: To investigate the antifibrotic effects of sakuraso-saponin on a primary culture of human pterygium fibroblasts (HPFs) and normal human Tenon fibroblasts (HTFs) as compared to the effects of mitomycin C (MMC).

Methods: Samples of HPFs and HTFs were acquired during primary pterygium surgery. Cell toxicity, cell migration, and expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) were evaluated in HPFs and HTFs after treatment with sakuraso-saponin and MMC. To determine the possible mechanisms underlying the antifibrotic effects of sakuraso-saponin, the expression of phosphorylated Smad2/3 was evaluated after treatment with sakuraso-saponin and MMC.

Results: MMC (≥200 μg/mL) significantly reduced cell viability in both HPFs and HTFs, whereas sakuraso-saponin (1.0 μg/mL) decreased cell viability in HPFs only. Both sakuraso-saponin (1.0 μg/mL) and MMC (200 μg/mL) treatment significantly reduced the expression of α-SMA and TGF-β in HPFs (P < 0.05). It is interesting that the expression of α-SMA and TGF-β after treatment with sakuraso-saponin was significantly lower than that after treatment with MMC (P < 0.05). The expression of phosphorylated Smad2/3 protein was decreased by sakuraso-saponin and MMC in HPFs. Both sakuraso-saponin and MMC inhibited TGF-β1-induced cell migration as compared to the control in HPFs.

Conclusions: Sakuraso-saponin could be more effective than MMC for the reduction of fibrosis in HPFs. Our results might present the basis for its use as a promising candidate drug for adjuvant therapy to prevent recurrent pterygium after surgery.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Alkylating Agents / pharmacology*
  • Blotting, Western
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibrosis / drug therapy
  • Humans
  • Mitomycin / pharmacology*
  • Phosphorylation
  • Pterygium / drug therapy*
  • Pterygium / pathology*
  • Pterygium / surgery
  • Saponins / pharmacology*
  • Smad2 Protein / metabolism
  • Smad4 Protein / metabolism
  • Tenon Capsule / cytology
  • Transforming Growth Factor beta / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Alkylating Agents
  • SMAD2 protein, human
  • SMAD4 protein, human
  • Saponins
  • Smad2 Protein
  • Smad4 Protein
  • Transforming Growth Factor beta
  • sakurasosaponin
  • Mitomycin