Fisetin and Luteolin decrease inflammation and oxidative stress‐induced cytotoxicity in ARPE‐19 cells

Abstract

PurposeAge‐related macular degeneration (AMD) is the leading cause of blindness among the elderly in the western world. It represents not only a dramatic reduction in patients’ quality of life but also a significant burden to the general healthcare system. Yet, despite the severity of the disease much questions regarding the pathways of disease formation and progression are still unanswered and viable treatment options still undiscovered. Here, we evaluate the cytoprotective and anti‐inflammatory potential of fisetin and luteolin in human retinal pigment epithelial cells exposed to increased oxidative stress.MethodsARPE‐19 cells were treated with 4‐Hydroxynonenal (HNE) to simulate high levels of oxidative stress. Thereafter, fisetin or luteolin were added to the culture medium. The MTT and the lactate dehydrogenase assays were used to assess cellular toxicity. Inflammatory cytokines, as well as activation of transcription factors were measured using the ELISA method and a DNA‐binding transcription factor assay. To analyze the importance of SIRT1 and related pathways, the experiments were repeated after specific SIRT1 knock‐out using siRNA. Levels of intracellular SIRT1 were measured using Western Blot.ResultsFisetin and luteolin protected retinal pigment epithelial cells from oxidative stress‐induced cell death and exhibited potent anti‐inflammatory properties even after the initial insult. These effects seemed to be independent of NF‐κB or SIRT1.ConclusionsBioactive polyphenols, fisetin and luteolin are powerful anti‐inflammatory and anti‐oxidant agents and show potential for the development of drugs aimed at specific intracellular pathways that affect inflammation in AMD.