Indobufen attenuates cerebral ischemia–reperfusion injury by inhibiting the NF-κB/Caspase-1/GSDMD pathway
10.11665/j.issn.1000-5048.2025091701
- VernacularTitle:吲哚布芬通过抑制NF-κB/Caspase-1/GSDMD通路减轻脑缺血再灌注损伤的作用与机制研究
- Author:
Yiyin XU
1
;
Dan XU
;
Xue GOU
;
Weirong FANG
;
Yunman LI
;
Hua SHAO
;
Yongqing WANG
Author Information
1. 徐州医科大学药学院, 徐州 221004;东南大学附属中大医院药学部, 南京 210009;中国药科大学基础医学与临床药学学院, 南京 210009;众红生物工程创药研究院有限公司, 常州 213000;江苏省人民医院(南京医科大学第一附属医院)药学部, 南京210009
- Publication Type:Journal Article 期刊文章
- Keywords:
indobufen;
ischemia/reperfusion injury;
pyroptosis;
NF-κB/Caspase-1/GSDMD pathway;
HUVECs
- From:
Journal of China Pharmaceutical University
2026;57(2):246-255
- CountryChina
- Language:Chinese
-
Abstract:
Indobufen is a new generation of antiplatelet agents and has been shown to have antithrombotic effects in animal models. However, its therapeutic potential and mechanisms against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we evaluated the in vivo neuroprotective effects of indobufen through both pretreatment and posttreatment regimens in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vitro, human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were employed to investigate the relationship between indobufen and the pyroptosis-associated NF-κB/Caspase-1/GSDMD pathway. The pharmacodynamic tests revealed that indobufen ameliorated I/R injury by decreasing the level of thromboxane B2 (TXB2), infarct size, brain edema and neurological impairment in rats and rescuing cell pyroptosis in HUVECs. The underlying mechanisms were probably related to pyroptosis suppression by regulating the NF-κB/Caspase-1/GSDMD pathway. Overall, these studies indicate that indobufen exerts protective and therapeutic effects against I/R injury by pyroptosis suppression via downregulating NF-κB/Caspase-1/GSDMD pathway.
