Protective Effects of Curcumin Ester Prodrug, Curcumin Diethyl Disuccinate against H2O2-Induced Oxidative Stress in Human Retinal Pigment Epithelial Cells: Potential Therapeutic Avenues for Age-Related Macular Degeneration

Chawanphat Muangnoi, Umar Sharif, Pahweenvaj Ratnatilaka Na Bhuket, Pornchai Rojsitthisak, Luminita Paraoan

Research output: Contribution to journalArticle (journal)peer-review

28 Citations (Scopus)

Abstract

Oxidative stress-induced damage to the retinal pigmented epithelium (RPE), a specialised post-mitotic monolayer that maintains retinal homeostasis, contributes to the development of age-related macular degeneration (AMD). Curcumin (Cur), a naturally occurring antioxidant, was previously shown to have the ability to protect RPE cells from oxidative stress. However, poor solubility and bioavailability makes Cur a poor therapeutic agent. As prodrug approaches can mitigate these limitations, we compared the protective properties of the Cur prodrug curcumin diethyl disuccinate (CurDD) against Cur in relation to oxidative stress induced in human ARPE-19 cells. Both CurDD and Cur significantly decreased H2O2-induced reactive oxygen species (ROS) production and protected RPE cells from oxidative stress-induced death. Both drugs exerted their protective effects through the modulation of p44/42 (ERK) and the involvement of downstream molecules Bax and Bcl-2. Additionally, the expression of antioxidant enzymes HO-1 and NQO1 was also enhanced in cells treated with CurDD and Cur. In all cases, CurDD was more effective than its parent drug against oxidative stress-induced damage to ARPE-19 cells. These findings highlight CurDD as a more potent drug compared to Cur against oxidative stress and indicate that its protective effects are exerted through modulation of key apoptotic and antioxidant molecular pathways.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume20
Issue number13
DOIs
Publication statusPublished - 9 Jul 2019
Externally publishedYes

Keywords

  • Blotting, Western
  • Cell Line
  • Cell Survival/drug effects
  • Curcumin/analogs & derivatives
  • Humans
  • Hydrogen Peroxide/pharmacology
  • Macular Degeneration/metabolism
  • Oxidative Stress/drug effects
  • Prodrugs/pharmacology
  • Reactive Oxygen Species/metabolism
  • Retinal Pigment Epithelium/cytology
  • Succinates/pharmacology

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