ArticleAnimal models and experimental medicine2026
Chrysin attenuates diabetes-induced retinal injury by inhibiting microglial GBP3/NLRP3/GSDMD-mediated pyroptosis.
Article in Animal models and experimental medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThis study was designed to investigate whether chrysin, a natural flavone, alleviates experimental diabetic retinal disease and to define a microglia-centered mechanism involving guanylate-binding protein 3 (GBP3) and NLR family pyrin domain containing 3 (NLRP3)-gasdermin D (GSDMD) pyroptosis signaling.
methodsStreptozotocin (STZ)-diabetic mice received vehicle or chrysin for 4 weeks, followed by assessment of fasting blood glucose, serum caspase-1 and interleukin-1β (IL-1β) levels, retinal histology, Evans blue leakage, and retinal immunofluorescence for glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA-1), with apoptosis measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). In vitro, BV2 microglia were exposed to high glucose with vehicle or chrysin. Cell viability (Cell Counting Kit-8), oxidative stress (reactive oxygen species and malondialdehyde), and pyroptosis-associated markers were analyzed by Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence. RNA sequencing (RNA-seq) profiled transcriptional responses, and small interfering RNA (siRNA) was used to knock down GBP3.
resultsIn STZ-diabetic mice, chrysin reduced fasting glucose and circulating caspase-1 and IL-1β, partially preserved retinal thickness, and decreased vascular leakage. Chrysin attenuated GFAP upregulation, reduced IBA-1 signals, and lowered TUNEL-positive cells. In BV2 cells, chrysin improved viability, reduced oxidative stress, and suppressed NLRP3-GSDMD activation. RNA-seq highlighted chrysin-responsive pyroptosis signatures and identified GBP3 as a regulated node. GBP3 knockdown reduced high-glucose-associated NLRP3 and Gsdmd expression and diminished GSDMD cleavage.
conclusionsChrysin protects the diabetic retina and suppresses microglial pyroptosis via a GBP3-linked NLRP3-GSDMD axis.
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