Hot-Air-Dried Eruca sativa Mill. Extracts Prevent Retinal Inflammation and Unfolded Protein Responses in ARPE-19 Cells

Abstract

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) constitute leading causes of irreversible visual impairment; both are pathologically linked to chronic inflammation and endoplasmic reticulum (ER) stress in retinal pigment epithelial (RPE) cells. This study aimed to investigate the protective effects of hot-air-dried Eruca sativa Mill. extract (ESH) on lipopolysaccharide (LPS)- and thapsigargin (Tg)-induced inflammatory and ER stress responses, respectively, in ARPE-19 cells. ESH pretreatment significantly suppressed LPS-induced phosphorylation of nuclear factor kappa B (NF-κB), inhibitor of kappa B alpha, and c-Jun N-terminal kinase, indicating effective inhibition of inflammatory signaling cascades. At the transcriptional level, ESH markedly attenuated the expression of tumor necrosis factor-α mRNA, suggesting downstream prevention of NF-κB–mitogen-activated protein kinase-mediated inflammatory gene activation. Under ER stress conditions, ESH significantly attenuated the upregulation of CCAAT/enhancer-binding protein (C/EBP) homologous protein and X-box binding protein-1, along with reductions in the expressions of cleaved caspase-3 and −9, indicating mitigation of ER stress-associated retinal apoptosis. Additionally, ESH prevented Tg-inducible vascular endothelial growth factor (VEGF) mRNA expression, VEGF protein secretion, and intracellular calcium level. Strong positive correlations were observed between intracellular calcium and VEGF secretion (r = 0.888), and between VEGF mRNA and protein levels (r = 0.843), supporting a potential mechanistic link. Collectively, these findings demonstrate that ESH modulates inflammatory, ER stress, apoptotic, and angiogenic pathways, suggesting its potential as a functional dietary supplement to mitigate RPE dysfunction in AMD and DR.