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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1538697
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Background: Endothelial dysfunction-induced microcirculation impairment and the no-reflow phenomenon are the leading causes of cardiac ischemia/reperfusion (I/R) injury. There is an urgent need to elucidate the underlying mechanism of I/R-mediated endothelial dysfunction and to identify effective drugs for treatment. Scutellarin (SCU), a flavonoid compound, has been extensively studied because of its various pharmacological properties, including its potent protective effects on the cardiovascular system. However, the anti-endothelial dysfunction efficacy and mechanisms of action of SCU have not been investigated. Approach and Results: An in vivo I/R injury model was established using coronary artery ligation and release. An oxygen-glucose deprivation/oxygen-glucose resupply (OGD/OGR) approach was used to establish an in vitro I/R injury model. We evaluated the effects of SCU on endothelial dysfunction under I/R conditions, both in vivo and in vitro. SCU pretreatment promoted vasodilation and reperfusion of blood flow, inhibited myocardial injury and infarction, and improved cardiac function in I/R rats. Additionally, SCU inhibited cell membrane damage, reactive oxygen species (ROS) accumulation, inflammation, nitric oxide (NO) reduction, endothelin 1 (ET-1) elevation and increase in the expression levels of vascular endothelial growth factor (VEGF) and von willebrand factor (vWF) in endothelial cells. Mechanistically, SCU rescued the lysosomal flow and autophagic flux disrupted by I/R through upregulating cathepsin D (CTSD) levels. Knockdown of CTSD or treatment with the CTSD inhibitor pepstatin A (P.A) abrogated the protective effects of SCU on endothelial cells under I/R conditions. Conclusion: We demonstrated that SCU, via upregulation of CTSD levels in endothelial cells, rescued autophagy-lysosomal function and alleviated I/R-mediated endothelial dysfunction. Thus, SCU is a potential therapeutic drug for the prevention and treatment of cardiac I/R injury.
Keywords: ischemia/reperfusion injury, endothelial dysfunction, Scutellarin, Autophagy-lysosomal function, Cathepsin D
Received: 20 Dec 2024; Accepted: 12 Feb 2025.
Copyright: © 2025 Zhuang, Chen, Wu, Wang, Kang, Xiong and Huang. 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:
Xianzhang Huang, Department of Laboratory Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong, 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.
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