Puerarin inactivates NLRP3-mediated pyroptotic cell death to alleviate cerebral ischemia/reperfusion (I/R) injury through modulating the LncRNA DUXAP8/miR-223-3p axis

[摘要] NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion (I/R) injury, and the aim of this study is to investigate the potential utilization of the Chinese medicine, Puerarin, in treating this disease. Through conducting in vitro and in vivo experiments, the present study illustrated that Puerarin regulated LncRNA double homeobox A pseudogene 8 (DUXAP8)/miR-223-3p axis to inactivate NLRP3-mediated pyroptotic cell death, resulting in the attenuation of I/R injury. Specifically, the cerebral I/R injury in rat models and hypoxia/reoxygenation (H/R) in primary hippocampus neuron (PHN) cells were inducted, which were subsequently exposed to Puerarin treatment. As expected, we validated that Puerarin suppressed cell pyroptosis and rescued cell viability in I/R rat hippocampus tissues and H/R PHN cells. Next, through bioinformatics analysis, we noticed that miR-223-3p targeted both LncRNA DUXAP8 and NLRP3 mRNA, and both LncRNA DUXAP8 ablation and miR-223-3p overexpression inactivate NLRP3-mediated cell pyroptosis to rescue cell viability in H/R PHN cells. Interestingly, we evidenced that Puerarin restrained LncRNA DUXAP8 expressions, but upregulated miR-223-3p in I/R rat tissues and H/R PHN cells, and the protective effects of Puerarin on H/R PHN cells were abrogated by overexpressing LncRNA DUXAP8 and silencing miR-223-3p. Collectively, we concluded that Puerarin regulated LncRNA DUXAP8/miR-223-3p/NLRP3 signaling cascade to attenuate I/R injury.

[学科分类] 仪器

[关键词] Cerebral ischemia/reperfusion;Puerarin;LncRNA DUXAP8;miR-223-3p;NLRP3-mediated cell pyroptosis