# Hesperidin and Hesperetin from Orange Peel Water Extract Protect against NaIO3‑Induced Oxidative Damage in Retinal Pigment Epithelial Cells by Modulating PI3K/Akt/HIF-1α/BNIP3 Signaling

## TL;DR

Orange peel extract and its compounds protect retinal cells from oxidative damage, suggesting potential for preventing age-related macular degeneration.

## Contribution

This study identifies hesperidin and hesperetin in orange peel extract as protective agents against retinal damage via specific signaling pathways.

## Key findings

- OPWE reduced oxidative stress and apoptosis in retinal cells via PI3K/Akt and HIF-1α/BNIP3 pathways.
- Hesperetin showed comparable protective effects to OPWE, restoring cell viability and inhibiting ROS production.
- Oral OPWE maintained retinal morphology and function in mice with NaIO3-induced damage.

## Abstract

Age-related macular degeneration (AMD) is a leading cause
of blindness
in the elderly, with oxidative stress a major causative factor. Orange
peel, rich in polyphenols and flavonoids, possesses potent antioxidant
and anti-inflammatory activities. This study evaluated the protective
effects of an ultrasound-assisted aqueous extract (OPWE) of orange
peel and its major components, hesperidin and hesperetin, against
sodium iodate (NaIO3)-induced retinal damage. Component
identification was performed using 3D-HPLC and LC/MS, and the antioxidant
capacity was determined using the DPPH and ABTS assays. In
vitro, OPWE reduced oxidative stress, mitochondrial dysfunction,
and apoptosis in NaIO3-treated ARPE-19 cells through the
PI3K/Akt and HIF-1α/BNIP3 pathways. Notably, hesperetin exhibited
comparable protective effects to OPWE, restoring cell viability and
inhibiting ROS production. In vivo, oral administration
of OPWE maintained retinal morphology and function in mice induced
by NaIO3. These findings suggest that OPWE, especially
hesperetin, is a promising natural candidate for preventing oxidative
stress-related retinal degeneration and maintaining retinal health.