Sesamin inhibits cellular inflammation of microglial cells in the retina and alleviates diabetic retinopathy
Diabetic retinopathy (DR) is the most common micro-vascular complication of diabetes, and the leading cause of vision loss and blindness globally. Due to the unsatisfied outcome of current therapies, a novel strategy needs to be developed. BV2 microglial cells were treated with 25 natural compounds respectively in the stimulation of high glucose (HG), to screen for the potential candidate drug. Streptozotocin (STZ)- induced diabetic mice were injected with different doses of the candidate Sesamin every two days for one month. Then, its protective role and possible mechanism were evaluated. Sesamin was selected as candidate drug due to its inhibition on the secretion of tumor necrosis factor-α (TNFα) in the screen assay. Sesamin also dose-dependently inhibited mRNA levels of HG-induced inflammatory cytokines, including TNFα, interleukin (IL)-1β and IL-6, activated NF-κB signaling pathway, and reduced oxidative stress by decreasing reactive oxygen species levels and increasing antioxidant enzymes in the BV2 and primary retinal microglia. Additionally, Sesamin alleviated brain-retinal barrier breakdown by Evan's blue leakage assay and reduced inflammation in Streptozotocin-induced diabetic mice. In conclusion, Sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, suggesting that Sesamin might serve as a candidate drug for DR treatment.