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Corilagin alleviates ferroptosis in diabetic retinopathy by activating the Nrf2 signaling pathway.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Oct; Vol. 179, pp. 117409. Date of Electronic Publication: 2024 Sep 08. - Publication Year :
- 2024
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Abstract
- Background and Purpose: Diabetic retinopathy (DR) is a prevalent complication of diabetes, with a rising global incidence, and can result in significant vision impairment and potential blindness in adults. Corilagin (COR) has been shown to regulate several pathological processes. However, the specific protective role and mechanism of action of COR in DR remain unknown.<br />Experimental Approach: The protective effects and mechanisms of COR in DR were examined using the ARPE-19 cell line and C57BL/6 mice. Intraretinal tissue damage and molecular markers were evaluated to investigate the impact of COR on oxidative stress and cell death pathways.<br />Key Results: In vitro, COR significantly reduced the cytotoxic effects of high glucose (HG) on ARPE-19 cells. Furthermore, COR also effectively decreased HG-induced lipid peroxidation, iron deposition, and ferroptosis and reduced damage to retinal tight junction proteins. Similarly, an in vivo study of streptozotocin (STZ)-induced DM mice showed that the daily gavage of COR for eight weeks notably alleviated DR. Mechanistically, COR activated the Nrf2 antioxidant signaling pathway both in vivo and in vitro, preventing HG-induced alterations in morphological and biochemical parameters. Notably, our study demonstrated that compared with controls, Nrf2 knockout mice and siNrf2-treated cells were more vulnerable to ferroptosis under HG conditions, and the protective effect of COR on DR was substantially diminished in these models.<br />Conclusion and Implications: These data indicate that COR has a protective effect against HG-induced retinal injury via a mechanism associated with the Nrf2-dependent antioxidant pathway and ferroptosis regulation.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Male
Cell Line
Mice, Knockout
Glucose metabolism
Glucose toxicity
Antioxidants pharmacology
Retinal Pigment Epithelium drug effects
Retinal Pigment Epithelium metabolism
Retinal Pigment Epithelium pathology
NF-E2-Related Factor 2 metabolism
Hydrolyzable Tannins pharmacology
Ferroptosis drug effects
Diabetic Retinopathy drug therapy
Diabetic Retinopathy pathology
Diabetic Retinopathy metabolism
Signal Transduction drug effects
Mice, Inbred C57BL
Glucosides pharmacology
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental complications
Diabetes Mellitus, Experimental metabolism
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 179
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 39243434
- Full Text :
- https://doi.org/10.1016/j.biopha.2024.117409