In age-related macular degeneration, N-retinylidene-N-retinylethanolamine (A2E) accumulates in retinal pigment epithelium (RPE) cells and generates oxidative stress, which further induces cell death. Polyphenols are well known for their antioxidant and beneficial effects on vision. Chrysanthemum boreale Makino (CB) flowers, which contain flavonoids, have antioxidant activity. We hypothesized that polyphenols in ethanolic extracts of CB (CBE) and its fractions suppressed A2E-mediated ARPE-19 cell damage, a human RPE cell line. CBE is rich in polyphenols, shows antioxidant activity, and suppresses intracellular accumulation of A2E and cell death induced by A2E. Among the five fractions, the polyphenol content and antioxidant effect were in the order of the ethyl acetate fraction (EtOAc) > butanol fraction (BuOH) > hexane fraction (Hex) > dichloromethane fraction (CH₂Cl₂) > water fraction (H₂O). In contrast, the inhibitory ability of A2E accumulation and A2E-induced cell death was highest in H₂O, followed by BuOH. In the correlation analysis, polyphenols in the H₂O and BuOH fractions had a significant positive correlation with antioxidant effects, but no significant correlation with cell damage caused by A2E. Our findings suggest that substances other than polyphenols present in CBE can suppress the effects of A2E, and further research is needed.

Age-related macular degeneration (AMD) is a major cause of irreversible loss of vision with 80–90% of patients demonstrating dry type AMD. Dry AMD could possibly be prevented by polyphenol-rich medicinal foods by the inhibition of N-retinylidene-N-retinylethanolamine (A2E)-induced oxidative stress and cell damage. Arctium lappa L. (AL) leaves are medicinal and have antioxidant activity. The purpose of this study was to elucidate the protective effects of the extract of AL leaves (ALE) on dry AMD models, including in vitro A2E-induced damage in ARPE-19 cells, a human retinal pigment epithelial cell line, and in vivo light-induced retinal damage in BALB/c mice. According to the total phenolic contents (TPCs), total flavonoid contents (TFCs) and antioxidant activities, ALE was rich in polyphenols and had antioxidant efficacies on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2′,7′-dichlorofluorescin diacetate (DCFDA) assays. The effects of ALE on A2E accumulation and A2E-induced cell death were also monitored. Despite continued exposure to A2E (10 μM), ALE attenuated A2E accumulation in APRE-19 cells with levels similar to lutein. A2E-induced cell death at high concentration (25 μM) was also suppressed by ALE by inhibiting the apoptotic signaling pathway. Furthermore, ALE could protect the outer nuclear layer (ONL) in the retina from light-induced AMD in BALB/c mice. In conclusion, ALE could be considered a potentially valuable medicinal food for dry AMD.