The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1365642
This article is part of the Research Topic Advances and Challenges in Stroke Therapy: A Regenerative Prospective - Volume II View all 9 articles
Lithocarpus polystachyus Rehd. ameliorates cerebral ischemia/reperfusion injury through inhibiting PI3K/AKT/NF-κB pathway and regulating NLRP3-mediated pyroptosis
Provisionally accepted- 1 Zunyi Medical University, Zunyi, Guizhou Province, China
- 2 Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China
Cerebral ischemia/reperfusion injury (CIRI) exacerbates neuronal damage by enhancing neuroinflammation and oxidative stress. Reactive oxygen species (ROS) can trigger the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, initiating and amplifying inflammatory responses. Thus, the inhibition of the ROS/NF-κB/NLRP3 axis may offer a promising therapeutic approach for CIRI. Sweet tea (ST) comprises several bioactive components, such as phlorizin, trilobatin, and phloretin, with diverse pharmacological activities. However, it remains uncertain whether ST can confer protection against CIRI. In this study, we aimed to investigate the impact and potential underlying mechanism of ST in the context of CIRI. Our results revealed that ST treatment significantly ameliorated brain damage in rats subjected to CIRI by mitigating mitochondrial oxidative stress and neuroinflammation. Additionally, we identified the PI3K/AKT/NF-κB pathway and the NLRP3-mediated pyroptosis axis as crucial processes, with NLRP3 emerging as a primary target in the protective effects of ST. Most intriguingly, molecular docking suggested direct interactions between the main compounds of ST and NLRP3, implying that NLRP3 holds promise as a therapeutic target for ST-induced cerebral protection. In summary, our findings demonstrate that ST safeguards against CIRI-induced neuronal loss, neuroinflammation and oxidative stress through the inhibition of the PI3K/AKT/NF-κB pathway and the regulation of NLRP3-mediated pyroptosis.
Keywords: ischemic stroke, Lithocarpus polystachyus Rehd., pyroptosis, PI3K/Akt/NF-κB, Oxidative Stress, Inflammation
Received: 04 Jan 2024; Accepted: 09 Sep 2024.
Copyright: © 2024 Liu, Wu, Wang, Zhan, Zhang, Gao and Gong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qihai Gong, Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.