{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:08:29Z","timestamp":1792066109828,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T00:00:00Z","timestamp":1692576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research (DSR) at the University of Tabuk, Tabuk, Saudi Arabia","award":["S-1442-0164"],"award-info":[{"award-number":["S-1442-0164"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Stroke ranks as the world\u2019s 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.<\/jats:p>","DOI":"10.3390\/ph16081182","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T08:53:31Z","timestamp":1692608011000},"page":"1182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Quercetin Alleviated Inflammasome-Mediated Pyroptosis and Modulated the mTOR\/P70S6\/P6\/eIF4E\/4EBP1 Pathway in Ischemic Stroke"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4909-7723","authenticated-orcid":false,"given":"Abdullah","family":"Alattar","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 47713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Alshaman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 47713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf S.","family":"Althobaiti","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 21944, Taif 21944, Saudi Arabia"},{"name":"Addiction and Neuroscience Research Unit, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghareb M.","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, University of Tabuk, Tabuk 47713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howaida S.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Assuit University, Assuit 71515, Egypt"},{"name":"Department of Pharmacology, Faculty of Medicine, University of Tabuk, Tabuk 47713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waleed Salman","family":"Khubrni","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 47713, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil Ok","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6925-7697","authenticated-orcid":false,"given":"Najeeb Ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sttam Bin Abdul Aziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5415-2179","authenticated-orcid":false,"given":"Fawad Ali","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Histology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1016\/S0140-6736(06)68770-9","article-title":"Global and regional burden of disease and risk factors, 2001: Systematic analysis of population health data","volume":"367","author":"Lopez","year":"2006","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Caplan, L.R. 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