Role of quercetin in protecting ARPE-19 cells against H2O2-induced injury via nuclear factor erythroid 2 like 2 pathway activation and endoplasmic reticulum stress inhibition

Abstract

Age‑related macular degeneration (AMD) is a common cause of irreversible blindness in the elderly in the western world. Research has demonstrated that degenerative and progressive conditions of retinal pigmented epithelial (RPE) cells are the key pathogenic mechanisms in AMD. Previous research has indicated the anti‑apoptosis, anti‑oxidant, anti‑inflammatory and anti‑cancer properties of quercetin. Therefore, the present study aimed to investigate the protective effects of quercetin on the ARPE‑19 human retinal pigment epithelial cell line. ARPE‑19 cells were pretreated with various concentrations of quercetin (0‑80 µM) before exposure to 300 µM H2O2. Cell viability was assessed and reactive oxygen species (ROS) were determined. The importance of the NF‑E2‑related factor 2 (Nrf2) signaling pathway was corroborated by western blotting and immunostaining. The protein expression levels of endoplasmic reticulum‑associated stress responsive genes and apoptotic markers were assessed by western blotting. The results demonstrated that in the H2O2 group, cell viability was weakened, but preserved in quercetin group in a dose‑dependent manner, particularly at 20 µM. The level of ROS decreased in the quercetin group compared with the control groups. In the quercetin group, the expression levels of Nrf2 and phase II enzymes (NQO1 and HO‑1) were increased, whereas the levels of ER stress markers (binding of immunoglobulin protein, CCAAT/enhancer‑binding protein homologous protein and phosphorylated eukaryotic translation initiation factor 2α) were reduced. Cell apoptosis‑associated protein expression levels were altered, with the increase of B‑cell lymphoma 2 and reduction of Bcl‑2 X‑associated protein. In conclusion, quercetin protected ARPE‑19 cells from H2O2‑induced cytotoxicity by activating the Nrf2 pathway, inhibiting ER stress and targeting anti‑apoptotic proteins.

Protective effects of quercetin in a rodent model of anterior ischemic optic neuropathy (rAION)

“…Previous studies have shown that Qcn serves as a free radical scavenger and with properties, such as anti-apoptosis, anti-oxidant, anti-inflammatory, and anti-cancer [13]. In the retina, we found that Qcn protected ARPE-19 cells from oxidative stress injury [14]. Other studies reported that Qcn has protective effects in the retina ischemia-reperfusion injury [15], ocular inflammation [16], and neuroprotective effects on RGC in glaucoma [17].…”

Phenolic Composition, Antioxidant Properties, and Inhibition toward Digestive Enzymes with Molecular Docking Analysis of Different Fractions from Prinsepia utilis Royle Fruits

“…Cilla et al [36] also found that the bioaccessible, flavonoid-rich fractions of citrus fruit pulps dramatically decreased the intracellular ROS generation of Caco-2 cells induced by H 2 O 2 [36]. Moreover, another previous study also pointed out that quercetin inhibited the intracellular ROS generation of H 2 O 2 -induced ARPE-19 cells via nuclear factor erythroid 2-like 2 pathway activation and endoplasmic reticulum stress inhibition [37]. Although the inhibitory effects of various plant materials on the intracellular ROS generation of H 2 O 2 -induced cells may be significantly different, all of the aforementioned studies pointed out that the phenolics contributed significantly to the ROS inhibitory activity, which was in agreement with the findings obtained in the present work.…”

Protective Effects of Flavonoids in Acute Models of Light-Induced Retinal Degeneration

“…Earlier studies in cultured human RPE cells also demonstrated that quercetin can protect these cells from oxidative stress via inhibition of pro-inflammatory markers and inhibition of the intrinsic apoptosis pathways (Cao X et al, 2010, Kook D et al, 2008, Weng S et al, 2017. difference was observed between mice kept in the dark and those exposed to light after treatment with flavonoids.…”