Lemon Peel Water Extract: A Novel Material for Retinal Health, Protecting Retinal Pigment Epithelial Cells against Dynamin-Related Protein 1-Mediated Mitochondrial Fission by Blocking ROS-Stimulated Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Pathway

  • Antioxidants (Basel). 2024 Apr 27;13(5):538. doi: 10.3390/antiox13050538.
Shang-Chun Tsou  1 ,  Chen-Ju Chuang  2 ,  Inga Wang  3 ,  Tzu-Chun Chen  4 ,  Jui-Hsuan Yeh  4 ,  Chin-Lin Hsu  1 ,  Yu-Chien Hung  5 ,  Ming-Chung Lee  6 ,  Yuan-Yen Chang  7  8 ,  Hui-Wen Lin  9
Affiliations
  • 1. Department of Nutrition, Chung Shan Medical University, Taichung 40201, Taiwan.
  • 2. Emergency Department, St. Martin De Porres Hospital, Chiayi 60069, Taiwan.
  • 3. Rehabilitation Sciences & Technology, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
  • 4. Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
  • 5. Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
  • 6. Brion Research Institute of Taiwan, New Taipei City 23143, Taiwan.
  • 7. Department of Microbiology and Immunology, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
  • 8. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
  • 9. Department of Optometry, Asia University, Taichung 413305, Taiwan.
PMID: 38790643 DOI: 10.3390/antiox13050538
Abstract

Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in Antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of Flavonoids and Polyphenols, against NaIO3-induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved Caspase-3 protein expression in RPE cells in NaIO3-induced mice. The effect of LUWE was achieved through the suppression of Apoptosis and the associated proteins, such as cleaved PARP and cleaved Caspase-3, as suggested by NaIO3-induced ARPE-19 cell models. This is because LUWE reduced reactive oxygen species-mediated mitochondrial fission via regulating p-Drp-1 and Fis1 expression. We further confirmed that LUWE suppresses the expression of p-MEK-1/2 and p-ERK-1/2 in NaIO3-induced ARPE-19 cells, thereby providing the protection described above, which was confirmed using PD98059 and U0126. These results indicated that LUWE prevents mitochondrial oxidative stress-mediated RPE damage via the MEK/ERK pathway. Elucidation of the molecular mechanism may provide a new protective strategy against retinal degeneration.

Keywords
apoptosis; lemon peel ultrasonic-assisted water extract (LUWE); reactive oxygen species (ROS); retinal degeneration; sodium iodate (NaIO3).
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