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Edaravone Dexborneol regulates the endothelial PPARγ-PON1 axis to inhibit high-cholesterol-induced atherosclerosis.

Created on 06 Jul 2026

Authors

Fengming Guo, Yuxin Liu, Wenjun Qiu, Xueyu Han, Yipeng Gao, Xin Liu, Si Hui Huang, Jingjun Lv, Qi-Zhu Tang, Bo Yang, Bo Shen

Published in

Clinical science (London, England : 1979). Jul 06, 2026. Epub Jul 06, 2026.

Abstract

Atherosclerosis, a primary cause of ischemic diseases, is driven by excessive oxidative stress. Edaravone Dexborneol, a clinically used antioxidant, has demonstrated potent protective effects in cerebral ischemia. However, its role in atherosclerosis remains unexplored. In this study, atherosclerosis models were constructed using Apoe-/- mice fed a high-fat diet. Edaravone Dexborneol treatment significantly attenuated aortic atherosclerosis progression, evidenced by reduced advanced plaque burden and improved hemodynamic parameters at the aortic root. The treatment also suppressed oxidative stress, leading to decreased low-density lipoprotein (LDL) oxidation and reduced oxidized LDL (ox-LDL) accumulation in aortic tissues and endothelial cells. Mechanistically, RNA sequencing and Western blot analyses revealed that Edaravone Dexborneol alleviates oxidative damage by activating peroxisome proliferator-activated receptor gamma (PPARγ) and upregulating paraoxonase 1 (PON1) expression. In human umbilical vein endothelial cells (HUVECs), PON1 knockdown partially abolished the antioxidant effects of Edaravone Dexborneol, while PPARγ inhibition reversed its induction of PON1. Furthermore, the combination of Edaravone Dexborneol with Rosuvastatin exhibited synergistic anti-atherogenic effects superior to Rosuvastatin alone. In conclusion, Edaravone Dexborneol attenuates atherosclerosis via the PPARγ/PON1 pathway, highlighting its potential as an antioxidant-based therapeutic strategy for atherosclerotic disease.

PMID:
42406509
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.

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