ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1631076
Ginsenoside Rb1 mitigates atherosclerosis in part through modulating FTO-mediated m 6 A RNA modification in NETs-induced endothelial activation
Provisionally accepted
- 1Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
- 2Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Background: Ginsenoside Rb1 (Rb1) exerts pharmacological effects in attenuating the progression of atherosclerosis. However, whether the anti-atherosclerotic effects of Rb1 involve suppressing neutrophil extracellular traps (NETs)-induced endothelial activation and whether N 6 -methyadenosine (m 6 A) RNA modification is mechanistically implicated in this process remain unknown. Methods: High fat diet (HFD)-fed Apoe -/-mice were subjected to histological, immunohistological and molecular biological analyses. Moreover, NETs-induced endothelial activation and m 6 A RNA methylation were assessed in human aortic endothelial cells (HAECs). Results: Rb1 mitigated atherosclerotic lesions and endothelial activation in vivo. Rb1 diminished adhesion of neutrophils and monocytes to NETs-stimulated HAECs, offset NETs-upregulated endothelial expression of ICAM1, VCAM1, SELE and SELP, and counteracted NETs-induced endothelial barrier impairment in vitro. NETs exposure significantly decreased the level of m 6 A RNA methylation and increased the expression of demethylase fat mass and obesity-associated protein (FTO) in HAECs, whereas Rb1 treatment enhanced m 6 A RNA methylation and reduced FTO expression in the NETs-stimulated HAECs. Overexpression of FTO abrogated the protective effects of Rb1 against NETs-induced endothelial activation in HAECs. Furthermore, Fto overexpression in endothelial cells partially abolished Rb1-confered attenuation of atherosclerotic pathologies and the aortic expression of Vcam1 in HFD-fed Apoe -/-mice. Conclusions: The work here demonstrates that Rb1 mitigates atherosclerosis in part by suppressing NETs-induced endothelial activation. Mechanistically, the pharmacological effects of Rb1 in attenuating NETs-induced endothelial activation are in part mediated by modulating FTO-mediated m 6 A RNA demethylation in endothelial cells.
Keywords: Ginsenoside Rb1, Atherosclerosis, Endothelial activation, neutrophil extracellular traps, Fat mass and obesity-associated protein
Received: 19 May 2025; Accepted: 14 Jul 2025.
Copyright: © 2025 Yang, Xiong, Tang, Wang, Cui, Chen and Zhang. 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: Yu Chen, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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