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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Stroke
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1490640
This article is part of the Research Topic From bench to bedside: Inflammation in Neurovascular Disorders and Stroke View all articles

Cynaroside: A Potential Therapeutic Agent Targeting Arachidonate 15-Lipoxygenase to Mitigate Cerebral Ischemia/Reperfusion Injury

Provisionally accepted
Yufeng Hu Yufeng Hu 1,2Wenpeng Cao Wenpeng Cao 1,2*Xingyu Yu Xingyu Yu 3*Tingting Long Tingting Long 1,2*Baofei Sun Baofei Sun 1,2*Shan Lei Shan Lei 2*Peng Xie Peng Xie 4Wenfeng Yu Wenfeng Yu 4*
  • 1 Department of Human Anatomy, Guiyang Medical College, Guiyang, Guizhou Province, China
  • 2 School of Basic Medical Sciences, Guizhou Medical University, Gui'an, Guizhou Province, China
  • 3 Guizhou Medical University, Guiyang, Guizhou Province, China
  • 4 Key Laboratory of Medical Molecular Biology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, China

The final, formatted version of the article will be published soon.

    Since cynaroside (Cyn) exhibits anti-inflammatory and antioxidant properties, it may prove to be useful in the treatment of cerebral ischaemia/reperfusion injury (I/R). The effects of Cyn on cerebral I/R injury were evaluated using a transient middle cerebral artery occlusion model (tMCAO) and a microglial cell model of oxygen and glucose deprivation/reoxygenation (OGD/R). Mice with MCAO treated with Cyn showed improvements in neurological deficits, decreased infarct volume and edema, and suppressed microglial activation. Moreover, Cyn demonstrated inhibition of tMCAO-induced Alox15. Through the application of bioinformatics, molecular docking, and biolayer interferometry techniques, it was shown that Cyn directly interacted with Alox15. Importantly, Cyn reduced the excessive production of M1 microgliaregulated pro-inflammatory cytokines NLRP3, ASC, and cleaved caspase-1 triggered by tMCAO or OGD/R. Additionally, Cyn reduced the overproduction of pro-inflammatory cytokines M1 microglia-regulated IL-1β and IL-18 in response to tMCAO or OGD/R. Cyn showed inhibitory effects on the expression of Tfrc, COX2, and Acsl4 in mice and BV-2 cells subjected to middle cerebral artery occlusions and oxygen-glucose deprivation/reperfusion treatments. These results indicate that Cyn may reduce cerebral ischemia/reperfusion (I/R) injury by attenuating inflammation and decreasing ferroptosis via the suppression of Alox15. An understanding of the molecular mechanisms that may be responsible for Cyn's therapeutic efficacy in ischemic stroke is obtained from this study. (1. revised some grammatical errors)

    Keywords: Cynaroside, Cerebral ischemia/reperfusion injury, ferroptosis, Inflammation, ALOX15

    Received: 16 Sep 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Hu, Cao, Yu, Long, Sun, Lei, Xie and Yu. 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:
    Wenpeng Cao, Department of Human Anatomy, Guiyang Medical College, Guiyang, 550004, Guizhou Province, China
    Xingyu Yu, Guizhou Medical University, Guiyang, 550025, Guizhou Province, China
    Tingting Long, Department of Human Anatomy, Guiyang Medical College, Guiyang, 550004, Guizhou Province, China
    Baofei Sun, Department of Human Anatomy, Guiyang Medical College, Guiyang, 550004, Guizhou Province, China
    Shan Lei, School of Basic Medical Sciences, Guizhou Medical University, Gui'an, 550025, Guizhou Province, China
    Wenfeng Yu, Key Laboratory of Medical Molecular Biology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou Province, 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.