Quercetin Alleviated Inflammasome-Mediated Pyroptosis and Modulated the mTOR/P70S6/P6/eIF4E/4EBP1 Pathway in Ischemic Strokeopen access
- Authors
- Alattar, Abdullah; Alshaman, Reem; Althobaiti, Yusuf S.; Soliman, Ghareb M.; Ali, Howaida S.; Khubrni, Waleed Salman; Koh, Phil Ok; Rehman, Najeeb Ur; Shah, Fawad Ali
- Issue Date
- Aug-2023
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- ischemic stroke; mTOR pathway; NLRP3; Nrf2/HO-1; quercetin
- Citation
- Pharmaceuticals, v.16, no.8
- Indexed
- SCIE
SCOPUS
- Journal Title
- Pharmaceuticals
- Volume
- 16
- Number
- 8
- URI
- https://scholarworks.gnu.ac.kr/handle/sw.gnu/67677
- DOI
- 10.3390/ph16081182
- ISSN
- 1424-8247
- Abstract
- Stroke ranks as the world’s second most prevalent cause of mortality, and it represents a major public health concern with profound economic and social implications. In the present study, we elucidated the neuroprotective role of quercetin on NLRP3-associated pyroptosis, Nrf2-coupled anti-inflammatory, and mTOR-dependent downstream pathways. Male Sprague Dawley rats were subjected to 72 h of transient middle cerebral artery ischemia, followed by the administration of 10 mg/kg of quercetin. Our findings demonstrated that MCAO induced elevated ROS which were coupled to inflammasome-mediated pyroptosis and altered mTOR-related signaling proteins. We performed ELISA, immunohistochemistry, and Western blotting to unveil the underlying role of the Nrf2/HO-1 and PDK/AKT/mTOR pathways in the ischemic cortex and striatum. Our results showed that quercetin post-treatment activated the Nrf2/HO-1 cascade, reversed pyroptosis, and modulated the autophagy-related pathway PDK/AKT/mTOR/P70S6/P6/eIF4E/4EBP1. Further, quercetin enhances the sequestering effect of 14-3-3 and reversed the decrease in interaction between p-Bad and 14-3-3 and p-FKHR and 14-3-3. Our findings showed that quercetin exerts its protective benefits and rescues neuronal damage by several mechanisms, and it might be a viable neuroprotective drug for ischemic stroke therapy. © 2023 by the authors.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 수의과대학 > Department of Veterinary Medicine > Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.gnu.ac.kr/handle/sw.gnu/67677)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.