ReferenceID 1540
Chrysophanol postconditioning attenuated cerebral ischemia-reperfusion injury induced NLRP3-related pyroptosis in a TRAF6-dependent manner
Exp Neurol
Individuals who suffer from post-CA (cardiac arrest) brain injury experience higher mortality and more severe functional disability. Neuroinflammation has been identified as a vital factor in cerebral ischemia-reperfusio
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 1540
- Evidence Id
- 18130
- Core Evidence Id
- 18130
- Source Reference Id
- 3073
- Herb2 Reference Id
- HBREF003870
- Subject Paper Key
- HBIN020479_35932799
- Pubmed Id
- 35932799
- Doi
- 10.1016/j.expneurol.2022.114197
- Paper Title
- Chrysophanol postconditioning attenuated cerebral ischemia-reperfusion injury induced NLRP3-related pyroptosis in a TRAF6-dependent manner
- Paper Abstract
- Individuals who suffer from post-CA (cardiac arrest) brain injury experience higher mortality and more severe functional disability. Neuroinflammation has been identified as a vital factor in cerebral ischemia-reperfusion injury (CIRI) following CA. Pyroptosis induces neuronal death by triggering an excessive inflammatory injury. Chrysophanol possesses robust anti-inflammatory features, and it is protective against CIRI. The purpose of this research was to assess the effect of Chrysophanol postconditioning on CIRI-induced pyroptotic cell death, and to explore its underlying mechanisms. CIRI was induced in rats by CA and subsequent cardiopulmonary resuscitation, and PC12 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to imitate CIRI in vitro. It was found that post-CA brain injury led to a notable cerebral damage revealed by histopathological changes and neurological outcomes. The existence of pyroptosis was also confirmed in in vivo and in vitro CIRI models. Moreover, we further confirmed that Chrysophanol, the main bioactive ingredient of Rhubarb, significantly suppressed expressions of pyroptosis-associated proteins, e.g., NLRP3, ASC, cleaved-caspase-1 and N-terminal GSDMD, and inhibited the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6). Furthermore, NLRP3 overexpression neutralized the neuroprotection of Chrysophanol postconditioning, suggesting that pyroptosis was the major neuronal death pathway modulated by Chrysophanol postconditioning in OGD/R. Additionally, the neuroprotection of Chrysophanol postconditioning was also abolished by gain-of-function analyses of TRAF6. Finally, the results demonstrated that Chrysophanol postconditioning suppressed the interaction between TRAF6 and NLRP3. Taken together, our findings revealed that Chrysophanol postconditioning was protective against CIRI by inhibiting NLRP3-related pyroptosis in a TRAF6-dependent manner.
- Journal
- Exp Neurol
- Publish Year
- 2022
- Experiment Subject
- rat; pc12 cells
- Experiment Type
- Animal Experiment
- Phenotype Related
- Brain Injury; Neuroinflammation; Excessive Inflammatory Injury; Tumor; Pyroptosis; Cerebral Ischemia-reperfusion Injury; Neuronal Death
- Paper Title Cn
- Paper Title En
- Chrysophanol postconditioning attenuated cerebral ischemia-reperfusion injury induced NLRP3-related pyroptosis in a TRAF6-dependent manner
- Bilingual Status
- semi_complete