Protective Effects of Rosmarinic Acid Against Oxidative Damage and Atherosclerosis via the PI3K/AKT Pathway.

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-05-31 DOI:10.1016/j.fct.2025.115576

Tiantian Tang, Mingze Sun, Baiyuan Sha, Rui Liu, Zhiyang Ren, Liwei Li, Ye Zhang, Hao Wang, Kai Yu

引用次数: 0

Abstract

Rosmarinic acid (RosA), a water-soluble phenolic compound, was recognized as a healthy and effective agent in antioxidant and anti-cardiovascular disease therapy. In vitro, RosA inhibited the adverse effects of H₂O₂ on HUVEC cells, which resulted in a decrease of 80.4% in intracellular ROS content and 73% in MDA content, while increase of 126% in SOD activity, 114% in CAT activity, and 78% in GSH-Px activity. In addition, in vivo, RosA improved lipid accumulation, plaque formation, antioxidant enzyme activities, and MDA levels in the aorta of mice with high-fat-diet-induced AS. This study also demonstrated for the first time that RosA suppresses PI3K/AKT pathway hyperactivation-evidencend by reduced phosphorylation of PI3K (p-PI3K/PI3K: 62% in vivo, 82% in vitro) and AKT (p-AKT/AKT: 34% in vivo, 62% in vitro)-and validated its dual role in mitigating oxidative stress and AS progression through molecular docking and kinetic modeling.

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迷迭香酸通过PI3K/AKT通路对氧化损伤和动脉粥样硬化的保护作用。

迷迭香酸（RosA）是一种水溶性酚类化合物，被认为是一种健康有效的抗氧化和抗心血管疾病的药物。在体外，RosA抑制H2O2对HUVEC细胞的不良影响，使HUVEC细胞内ROS含量降低80.4%，MDA含量降低73%，SOD活性升高126%，CAT活性升高114%，GSH-Px活性升高78%。此外，在体内，RosA改善了高脂肪饮食诱导的AS小鼠主动脉的脂质积累、斑块形成、抗氧化酶活性和MDA水平。该研究还首次证明了RosA抑制PI3K/AKT通路的过度激活，这可以通过降低PI3K （p-PI3K/PI3K：体内62%，体外82%）和AKT （p-AKT/AKT：体内34%，体外62%）的磷酸化来证明，并通过分子对接和动力学模型验证了RosA在缓解氧化应激和AS进展中的双重作用。

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

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.