Chrysin attenuates diabetes‐induced retinal injury by inhibiting microglial GBP3/NLRP3/GSDMD‐mediated pyroptosis
6 affiliations
- 1School of Basic Medicine Nanchang Medical College Nanchang PR China
- 2Innovative Research Center for Major Disease Mechanisms and Intervention Nanchang Medical College Nanchang PR China
- 3School of Nursing Guangdong Pharmaceutical University Guangzhou PR China
- 4Shenzhen Binhai Aier Eye Hospital Shenzhen PR China
- 5Department of Ophthalmology The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University Nanchang PR China
- 6Chinese Academy of Medical Sciences & Peking Union Medical College Beijing PR China
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 blot, 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.
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BibTeX
@article{liu2026chrysin,
title = {{Chrysin attenuates diabetes‐induced retinal injury by inhibiting microglial GBP3/NLRP3/GSDMD‐mediated pyroptosis}},
author = {Qun Liu and Song‐min Wang and Xuan Chen and Yi‐rao You and Chen‐jiao Guo and Chang‐qin Xie and Lu‐lu Wang and Qi Liu and Lan Zhang and Jun‐tao Yang},
journal = {Animal Models and Experimental Medicine},
year = {2026},
month = sep,
doi = {10.1002/ame2.70293},
url = {https://doi.org/10.1002/ame2.70293},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Chrysin attenuates diabetes‐induced retinal injury by inhibiting microglial GBP3/NLRP3/GSDMD‐mediated pyroptosis
AU - Qun Liu
AU - Song‐min Wang
AU - Xuan Chen
AU - Yi‐rao You
AU - Chen‐jiao Guo
AU - Chang‐qin Xie
AU - Lu‐lu Wang
AU - Qi Liu
AU - Lan Zhang
AU - Jun‐tao Yang
PY - 2026
DA - 2026/09/24
JO - Animal Models and Experimental Medicine
DO - 10.1002/ame2.70293
UR - https://doi.org/10.1002/ame2.70293
AB - 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 blot, 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.
SN - 2096-5451
SN - 2576-2095
ER -