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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

1
Pharmaceutical Chemistry and Natural Products Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
2
Natural Products for Ageing and Chronic Diseases Research Unit, Chulalongkorn University, Bangkok 10330, Thailand
3
Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK
4
Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(13), 3367; https://doi.org/10.3390/ijms20133367
Received: 12 June 2019 / Revised: 3 July 2019 / Accepted: 5 July 2019 / Published: 9 July 2019
(This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration (AMD))
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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. View Full-Text
Keywords: age related macular degeneration; retinal pigment epithelium; oxidative stress; curcumin; curcumin diethyl disuccinate age related macular degeneration; retinal pigment epithelium; oxidative stress; curcumin; curcumin diethyl disuccinate
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Muangnoi, C.; Sharif, U.; Ratnatilaka Na Bhuket, P.; Rojsitthisak, P.; Paraoan, L. 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. Int. J. Mol. Sci. 2019, 20, 3367.

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