Protective Effect of <i>Chrysanthemum boreale</i> Flower Extracts against A2E-Induced Retinal Damage in ARPE-19 Cell

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