Chrysin attenuates diabetes‐induced retinal injury by inhibiting microglial
GBP3
/
NLRP3
/
GSDMD
Qun Liu, Song‐min Wang, Xuan Chen, Yi‐rao You, Chen‐jiao Guo, Chang‐qin Xie, Lu‐lu Wang, Qi Liu, Lan Zhang, Jun‐tao Yang Abstract
Background
This 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.
Methods
Streptozotocin (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.
Results
In 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.
Conclusions
Chrysin protects the diabetic retina and suppresses microglial pyroptosis via a GBP3‐linked NLRP3–GSDMD axis.