Quercetin Promotes Abdominal Aortic Aneurysm Regression Through the RAGE/PI3K/AKT/mTOR Axis

IF 1.5 4区 医学 Q4 CHEMISTRY, MEDICINAL
Xin Yang, Ying Wang, Guangyu Xin, Jie Li, Lei Xu, Guohua Zhang, Haotian Yang
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Abstract

Objective: Abdominal aortic aneurysms (AAA) are a common critical cardiovascular disease with high morbidity and mortality rates. Quercetin, a flavonoid and a traditional Chinese medicinal ingredient commonly found in vegetables and fruits, has a favorable inhibitory effect on experimental aneurysms without side effects. This study aimed to model elastase AAA and investigate the mechanism of action of quercetin in alleviating AAA. Methods: Quercetin was administered at a dose of 60 mg/kg once daily starting on the day of AAA induction for 5 weeks. The therapeutic effect of quercetin on AAA was demonstrated using biochemical assays, observation of pathological tissue sections, Elastic Van Gieson staining, immunohistochemistry, molecular docking simulations, and Western blot protein validation. Results: Our study showed that quercetin treatment significantly alleviated abdominal aortic vessel wall dilatation, elastin degradation and adhesion to surrounding tissues caused by elastase. Additionally, quercetin significantly inhibited the mRNA and protein expression of the receptor for advanced glycation end products(RAGE)/ phosphatidylinositol 3-kinase (PI3K)/ phosphatidylinositol 3-kinase (AKT) / mammlian target of rapamycin (mTOR) pathway. Conclusion: Quercetin can alleviate abdominal aortic injury caused by elastase via RAGE/PI3K/AKT/mTOR and provide experience in clinical use.
槲皮素通过RAGE/PI3K/AKT/mTOR轴促进腹主动脉瘤消退
目的:腹主动脉瘤(AAA)是一种常见的高发病率和死亡率的危重心血管疾病。槲皮素是一种类黄酮,是一种常见于蔬菜和水果中的中药成分,对实验性动脉瘤有良好的抑制作用,且无副作用。本研究拟建立弹性蛋白酶AAA模型,探讨槲皮素缓解AAA的作用机制。方法:自AAA诱导当日起,给予槲皮素60 mg/kg / d,连续5周。通过生化实验、病理组织切片观察、弹性Van Gieson染色、免疫组化、分子对接模拟、Western blot蛋白验证等方法验证槲皮素对AAA的治疗效果。结果:我们的研究表明,槲皮素治疗可显著缓解弹性蛋白酶引起的腹主动脉血管壁扩张、弹性蛋白降解和与周围组织的粘连。此外,槲皮素显著抑制晚期糖基化终产物(RAGE)/磷脂酰肌醇3-激酶(PI3K)/磷脂酰肌醇3-激酶(AKT) /哺乳动物雷帕霉素靶点(mTOR)通路受体的mRNA和蛋白表达。结论:槲皮素可通过RAGE/PI3K/AKT/mTOR通路减轻弹性蛋白酶所致的腹主动脉损伤,为临床应用提供经验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Natural Product Communications
Natural Product Communications 工程技术-食品科技
CiteScore
3.10
自引率
11.10%
发文量
254
审稿时长
2.7 months
期刊介绍: Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products. Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products. Natural Product Communications is a peer reviewed, open access journal studying all aspects of natural products, including isolation, characterization, spectroscopic properties, biological activities, synthesis, structure-activity, biotransformation, biosynthesis, tissue culture and fermentation. It covers the full breadth of chemistry, biochemistry, biotechnology, pharmacology, and chemical ecology of natural products.
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