Moscatilin alleviates oxidative stress and inflammatory response of Müller cells in diabetic retinopathy through suppressing the p38 mitogen-activated protein kinase/c-Jun N-terminal kinase and nuclear factor kappa-B signaling pathways

Diabetic retinopathy (DR), as the main ophthalmic complication of diabetes mellitus, is a major eye disorder contributing to blindness. Oxidative stress and inflammation in retinal Müller cells participate in the pathogenesis of DR. This work aims to study the biological role of moscatilin in the progression of DR and the underlying mechanism. High glucose (HG)-stimulated mouse primary retinal Müller cells and high-fat diet + streptozotocin (STZ)-induced DR mouse models were constructed as in vitro and in vivo models, respectively. The effects of moscatilin treatment on oxidative stress and inflammation in HG-stimulated Müller cells and DR mice were evaluated by detecting intracellular reactive oxygen species production, malondialdehyde levels, superoxide dismutase and catalase activities, glutathione/oxidized glutathione ratio, as well as proinflammatory cytokine levels through CM-H₂DCFDA staining, commercial kits, and enzyme-linked immunosorbent assay. Dual immunofluorescence staining of glial fibrillary acidic protein and vimentin was used to evaluate the development of Müller cells in mouse retinas. The activity of p38 mitogen-activated protein kinase (MAPK)/c-Jun N-terminal kinase (JNK) and nuclear factor kappa-B (NF-κB) signaling pathway was assessed through western blotting and immunofluorescence staining. Moscatilin pretreatment prevented HG-induced decrease in Müller cell viability. Moscatilin mitigated oxidative stress, inflammation, and extracellular matrix remodeling in HG-stimulated Müller cells and DR mice. Mechanically, moscatilin reduced the levels of receptor for advanced glycation end products, phosphorylated I-kappa-B-alpha, p-p65 NF-κB, p-p38 MAPK, and p-JNK in both HG-stimulated Müller cells and DR mice. Moscatilin plays an antioxidant and anti-inflammatory role in DR by inhibiting the p38 MAPK/JNK and NF-κB signaling pathways.