Eugenol restrains abdominal aortic aneurysm progression with down‐regulations on NF‐κB and COX‐2
Eugenol restrains abdominal aortic aneurysm progression with down‐regulations on NF‐κB and COX‐2
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DOI：
10.1002/ptr.7358
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发表时间：
2022-02
影响因子：
7.2
通讯作者：
Ziyi Zhai;Xian-jing Zhang;Yuchao Ding;Ziming Huang;Qian Li;Mingyue Zheng;Kenka Cho;Z. Dong;W. Fu;Zaixing Chen;B. Jiang
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文献类型：
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作者：
Ziyi Zhai;Xian-jing Zhang;Yuchao Ding;Ziming Huang;Qian Li;Mingyue Zheng;Kenka Cho;Z. Dong;W. Fu;Zaixing Chen;B. Jiang
腹主动脉瘤（AAA）是一种致死性疾病，目前尚无有效的治疗药物。本研究旨在评价丁香酚（4-烯丙基-2-甲氧基苯酚）对AAA的有效性及其潜在机制。丁香酚是丁香的主要活性成分。通过猪胰腺弹性蛋白酶（PPE）体外孵育和1% 3-氨基丙腈（BAPN）饲料建立小鼠AAA模型。根据AAA直径和组织病理学评价，PPE + BAPN治疗后从第0天到第15天观察到AAA持续进展。免疫荧光检测显示，随着AAA进展，CD 68、考克斯-2和NF-κB的表达持续增加。在通过AAA直径、苏木精-伊红染色和地衣红染色阐明丁香酚对AAA进展的有效性后，通过免疫组织化学和western blot进一步检测丁香酚对考克斯-2和NF-κB的下调。丁香酚不仅以剂量依赖性方式阻断AAA扩张并保护主动脉结构的完整性，而且具有较高的口服生物利用度。丁香酚的高效、高口服生物利用度和对考克斯-2/NF-κB的下调作用使其在未来AAA治疗中具有巨大的潜力。
Abdominal aortic aneurysm (AAA) is a lethal disease without available medicine for treatment. This study aimed to evaluate the efficiency of eugenol (4‐allyl‐2‐methoxyphenol) against AAA and the underlying mechanism. Eugenol is the major bioactive component of clove. A mouse AAA model was established through porcine pancreatic elastase (PPE) incubation peri‐adventitially and 1% 3‐aminopropanonitrile (BAPN) diet. Continuous AAA progression from day 0 to day 15 was observed after PPE plus BAPN treatment, according to the AAA diameter and histopathological evaluation. Accompanying with AAA progression, sustained increased expressions of CD68, COX‐2 and NF‐κB were observed through immunofluorescence assay. After elucidation the efficiency of eugenol against AAA progression by AAA diameter, hematoxylin–eosin staining and orcein staining, the down‐regulations of eugenol on COX‐2 and NF‐κB were further detected by immunohistochemistry and western blot. Eugenol not only blocked AAA expansion and protected the integrity of aortic structure in a dose‐dependent manner, but also held high oral bioavailability. Excellent efficiency, high oral bioavailability and down‐regulation on COX‐2/NF‐κB endowed eugenol great potential for future AAA therapy.