Obacunone Protects Retinal Pigment Epithelium Cells from Ultra-violet Radiation-induced Oxidative Injury

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 Feb 3

PMID 33535179

Citations 5

Authors

Da-Rui Huang

Chang-Ming Dai

Shu-Yan Li

Xiao-Feng Li

Affiliations

Soon will be listed here.

Abstract

Ultra-violet (UV) radiation (UVR) causes significant oxidative injury to retinal pigment epithelium (RPE) cells. Obacunone is a highly oxygenated triterpenoid limonoid compound with various pharmacological properties. Its potential effect in RPE cells has not been studied thus far. Here in ARPE-19 cells and primary murine RPE cells, obacunone potently inhibited UVR-induced reactive oxygen species accumulation, mitochondrial depolarization, lipid peroxidation and single strand DNA accumulation. UVR-induced RPE cell death and apoptosis were largely alleviated by obacunone. Obacunone activated Nrf2 signaling cascade in RPE cells, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization and nuclear translocation. It promoted transcription and expression of antioxidant responsive element-dependent genes. Nrf2 silencing or CRISPR/Cas9-induced Nrf2 knockout almost reversed obacunone-induced RPE cytoprotection against UVR. Forced activation of Nrf2 cascade, by Keap1 knockout, similarly protected RPE cells from UVR. Importantly, obacunone failed to offer further RPE cytoprotection against UVR in Keap1-knockout cells. , intravitreal injection of obacunone largely inhibited light-induced retinal damage. Collectively, obacunone protects RPE cells from UVR-induced oxidative injury through activation of Nrf2 signaling cascade.

Citing Articles

Obacunone, a Promising Phytochemical Triterpenoid: Research Progress on Its Pharmacological Activity and Mechanism.

Zhou Y, Gu J, Li J, Zhang H, Wang M, Li Y Molecules. 2024; 29(8).

PMID: 38675611 PMC: 11054759. DOI: 10.3390/molecules29081791.

Obacunone Photoprotective Effects against Solar-Simulated Radiation-Induced Molecular Modifications in Primary Keratinocytes and Full-Thickness Human Skin.

Montero P, Villarroel M, Roger I, Morell A, Milara J, Cortijo J Int J Mol Sci. 2023; 24(14).

PMID: 37511243 PMC: 10380981. DOI: 10.3390/ijms241411484.

Nomilin and Its Analogues in Citrus Fruits: A Review of Its Health Promotion Effects and Potential Application in Medicine.

Zhou Z, Yan Y, Li H, Feng Y, Huang C, Fan S Molecules. 2023; 28(1).

PMID: 36615463 PMC: 9822165. DOI: 10.3390/molecules28010269.

Obacunone alleviates ferroptosis during lipopolysaccharide-induced acute lung injury by upregulating Nrf2-dependent antioxidant responses.

Li J, Deng S, Li J, Li L, Zhang F, Zou Y Cell Mol Biol Lett. 2022; 27(1):29.

PMID: 35305560 PMC: 8933916. DOI: 10.1186/s11658-022-00318-8.

Obacunone Retards Renal Cyst Development in Autosomal Dominant Polycystic Kidney Disease by Activating NRF2.

Qiu Z, He J, Shao G, Hu J, Li X, Zhou H Antioxidants (Basel). 2022; 11(1).

PMID: 35052542 PMC: 8773305. DOI: 10.3390/antiox11010038.

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