Sesamin suppresses high glucose-induced microglial inflammation in the retina in vitro and in vivo.

ABSTRACT

Diabetic retinopathy (DR) is the most common microvascular complication in 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, stimulated by high glucose (HG) to screen for a potential candidate drug. Streptozotocin (STZ)-induced diabetic mice were injected with different doses of the candidate sesamin every 2 days for 1 mo. Then, its protective role and possible mechanism were evaluated. Sesamin was selected as the 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)-1ß, 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. In addition, sesamin alleviated brain-retinal barrier breakdown by Evans 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.NEW & NOTEWORTHY Sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, which suggests that sesamin might serve as a candidate drug for diabetic retinopathy treatment.