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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1525456
Naoqing formula alleviates acute ischaemic stroke-induced ferroptosis via activating Nrf2/xCT/GPX4 pathway
Provisionally accepted
Yujun Ye
*
Xuexin Xie
*
Yiming Bi
*
Qing Liu
*
Xuliang Weng
*
Lingling Qiu
*
He Zhao
Shangyan Hei
*
Ling Yang
*
Chengyin Wang
Weifeng Zhu
*
Ting Zeng
*- School of Health Management, Guangzhou Medical University, Guangzhou, China
Ferroptosis is a form of regulated cell death. The accumulation of iron in the brain is linked to trigger ferroptosis after an ischaemic stroke (IS). Naoqing formula (NQ) is a traditional Chinese medicine metabolites with the clinical function of activating blood circulation, which is applied to treat IS clinically in China. Methods: Mice and SH-SY5Y cells were utilized to investigate the protective effects and the underlying mechanism of NQ against middle cerebral artery occlusion (MCAO) induced acute ischaemic stroke (AIS) and neuronal cellular ferroptosis caused by ferroptosis inducer Erastin in vitro and in vivo. Utilizing molecular biological techniques, transcriptomics, and proteomics analyses, the role of NQ in Nrf2 regulation and ferroptosis was evaluated through the pharmacologic inhibition of Nrf2. Results: NQ attenuated AIS-induced neuronal damage and cerebral infarction by increasing cortical blood flow (CBF). Transcriptomics and proteomics analyses revealed that NQ might regulate lipid and iron metabolism through Nrf2 pathway. Additionally, NQ can protect AIS from ferroptosis by reducing oxidative stress and iron overload. Meanwhile, Nrf2, solute carrier family 7 member 11 (SLC7A11; also known as xCT) and glutathione peroxidase 4 (GPX4) were upregulated in NQ-treated AIS mice. Consistent with the results in vivo, NQ led to ferroptosis resistance upon exposure to a ferroptosisinducing compound through activation of Nrf2/xCT/GPX4 pathway in vitro. Notably, in vivo inhibition
Keywords: acute ischaemic stroke (AIS), Naoqing formula (NQ), Nrf2, ferroptosis, oxidative stress cerebral ischaemia/reperfusion injury cerebral ischaemia/reperfusion injury cerebral ischaemia/reperfusion injury (CIRI) Dryobalanops aromatica C.F.Gaertn.(Bing Pian), Components Metabolites
Received: 09 Nov 2024; Accepted: 28 Nov 2024.
Copyright: © 2024 Ye, Xie, Bi, Liu, Weng, Qiu, Zhao, Hei, Yang, Wang, Zhu and Zeng. 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:
Yujun Ye, School of Health Management, Guangzhou Medical University, Guangzhou, China
Xuexin Xie, School of Health Management, Guangzhou Medical University, Guangzhou, China
Yiming Bi, School of Health Management, Guangzhou Medical University, Guangzhou, China
Qing Liu, School of Health Management, Guangzhou Medical University, Guangzhou, China
Xuliang Weng, School of Health Management, Guangzhou Medical University, Guangzhou, China
Lingling Qiu, School of Health Management, Guangzhou Medical University, Guangzhou, China
Shangyan Hei, School of Health Management, Guangzhou Medical University, Guangzhou, China
Ling Yang, School of Health Management, Guangzhou Medical University, Guangzhou, China
Weifeng Zhu, School of Health Management, Guangzhou Medical University, Guangzhou, China
Ting Zeng, School of Health Management, Guangzhou Medical University, Guangzhou, China
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