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Eugenol restrains abdominal aortic aneurysm progression with dual targets on NF-κB and COX-2
  • +5
  • Baohong Jiang,
  • Ziyi Zhai,
  • Xianjing Zhang,
  • Yuchao Ding,
  • Ziming Huang,
  • Qian Li,
  • Mingyue Zheng,
  • Zaixing Chen
Baohong Jiang
Shanghai Institute of Materia Medica Chinese Academy of Sciences

Corresponding Author:[email protected]

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Ziyi Zhai
China Medical University
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Xianjing Zhang
Shanghai Institute of Materia Medica Chinese Academy of Sciences
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Yuchao Ding
China Medical University
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Ziming Huang
Shanghai Institute of Materia Medica Chinese Academy of Sciences
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Qian Li
China Medical University
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Mingyue Zheng
Shanghai Institute of Materia Medica Chinese Academy of Sciences
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Zaixing Chen
China Medical University
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Abstract

Background and Purpose: Abdominal aortic aneurysm (AAA) is a lethal disease without available medicine for treatment. As COX-2 and NF-κB are promising targets against AAA, eugenol, a novel candidate as a dual-target on COX-2 and NF-κB, was unearthed and evaluated it efficiency against AAA progression. Experimental Approach: AAA model was established using porcine pancreatic elastase (PPE) plus 3-aminopropanonitrile (BAPN). Dual-binding of eugenol with COX-2 and NF-κB was verified by molecular docking. The efficiency of eugenol against AAA progression was evaluated by hematoxylin-eosin staining and orcein staining. The downregulations of eugenol on COX-2 and NF-κB were detected by immunohistochemistry and western blot. The administration route of eugenol was further evaluated. Key Results: Based on the results of AAA progression, AAA model was confirmed to be set up at day 5 after PPE and BAPN induced, then the 5th day was defined as the starting time point for eugenol treatment. With AAA progression, macrophage infiltration, up-regulation of COX-2 and NF-κB was detected. After massive screening and molecular docking, eugenol was chosen because of its dual targets on COX-2 and NF-κB. Eugenol blocked AAA expansion and protected the integrity of aortic structure in a dose-dependent manner. Furthermore, the down-regulation of eugenol on COX-2 and NF-κB was further confirmed in vivo. Finally, high oral bioavailability was found as another advantage of eugenol. Conclusion and Implications: On the basis of dual-targets against COX-2 and NF-κB, high efficiency and oral bioavailability endowed eugenol great potential for future AAA therapy. KEYWORDS Abdominal aortic aneurysm, Eugenol, NF-κB, COX-2