ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1651873
This article is part of the Research TopicTargeted Drug Delivery and Mode of Action of Small Molecules in NeuroinflammationView all 9 articles
Elucidating Multifaceted targets of Marein in Cerebral Ischemia-Reperfusion Injury
Provisionally accepted
XINGXIA WANG1*
Jian Wang2
Ying Fan1
Meng Yuan1
Wanying Xie1
Yi Zhong1
Xinyao Huang1Yibo Zhang1
Yang Su1
Xuan Mao1
Jiaxin Zhan1Xingchun Wang3
Junxi Long1Xinrui Wang1- 1The Affiliated Hospital of Southwest Medical University, Luzhou, China
- 2Sichuan Cancer Hospital and Institute, Chengdu, China
- 3Hospital of Stomatology of Southwest Medical University, Luzhou, China
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Background: Cerebral ischemia-reperfusion injury (CIRI) is a major pathological event in stroke, leading to neuronal damage and neuroinflammation. Marein, a flavonoid derived from Coreopsis tinctoria, has demonstrated potential neuroprotective effects, yet its precise mechanisms in CIRI remain unclear. Methods: Marein-related targets were predicted using SwissTargetPrediction, and cerebral ischemia–reperfusion injury (CIRI)-related targets were obtained from GeneCards. Common targets were identified by Venn analysis, followed by protein–protein interaction network construction and GO/KEGG enrichment analysis. Molecular docking and 100-ns molecular dynamics simulations evaluated interactions between Marein/Edaravone and key targets (PTGS2, SRC, EGFR). In vitro, an oxygen–glucose deprivation/reperfusion model in HT22 cells was used to assess cell viability, reactive oxygen species production, and protein expression. Results: 64 common targets (including PTGS2, SRC, EGFR) were identified. Enrichment analyses highlighted involvement in calcium signaling, inflammatory responses, and kinase-mediated pathways. Molecular docking and dynamics confirmed stable binding of Marein to PTGS2, SRC, and EGFR, with favorable binding free energies. In vitro, Marein (≤40 μM) improved viability of OGD/R-exposed HT22 cells, reduced ROS accumulation, and downregulated PTGS2 and SRC expression. Conclusion: Marein exerts neuroprotective effects against CIRI by targeting PTGS2, SRC, and EGFR, modulating inflammatory and oxidative stress pathways. This study provides a mechanistic basis for Marein's potential in CIRI therapy.
Keywords: marein, Network Pharmacology, Cerebral ischemia-reperfusion injury, molecular docking, Molecular Dynamics Simulation
Received: 24 Jun 2025; Accepted: 10 Sep 2025.
Copyright: © 2025 WANG, Wang, Fan, Yuan, Xie, Zhong, Huang, Zhang, Su, Mao, Zhan, Wang, Long and Wang. 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: XINGXIA WANG, xingxiawang888@swmu.edu.cn
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