Artemisinin attenuated ischemic stroke induced pyroptosis by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway.
Biomed Pharmacother
; 177: 116894, 2024 Jun 14.
Article
en En
| MEDLINE
| ID: mdl-38878634
ABSTRACT
BACKGROUND:
To explore the neuroprotective mechanism of artemisinin against ischemic stroke from the perspective of NLRP3-mediated pyroptosis.METHODS:
Serum metabolomics technology was used to analyze the serum samples of mice, and KEGG metabolic pathway was analyzed for the different metabolites in the samples. PIT model and OGD/R model were used to simulate ischemic stroke damage in vivo and in vitro. Hoechst 33342 staining, Annexin V-FITC/PI staining and TUNEL staining were used to detect the pyroptosis rate of cells. The contents of IL-1ß and IL-18 in PC12 cells and serum of mice were detected by ELISA. The expressions of NLRP3, ASC-1, Caspase-1 and TXNIP in PC12 cells and mouse brain tissue were detected by Western Blot.RESULTS:
Serum metabolic profiles of animal models identified 234 different metabolites and 91 metabolic pathways. Compared with the Sham group and the Stroke+ART group, the KEGG pathway in the Stroke group was concentrated in the Necroptosis pathway associated with cell growth and death, and the NLRP3 inflammasome-mediated pyroptosis pathway was activated in the Necroptosis pathway after ischemic stroke. The results of in vivo and in vitro experiments showed that pretreatment with 10⯵M artemisinin reduced ROS production, decreased Δψm, reduced pyroptosis, maintained neuronal cell morphology, and down-regulated the contents of IL-1ß and IL-18 as well as the expression of key proteins of NLRP3, ASC-1, Caspase-1 and TXNIP(p<0.01).CONCLUSION:
Artemisinin can reduce neuronal pyroptosis induced by ischemic stroke by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2024
Tipo del documento:
Article