Promising remedies for cardiovascular disease: Natural polyphenol ellagic acid and its metabolite urolithins,Phytomedicine

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Promising remedies for cardiovascular disease: Natural polyphenol ellagic acid and its metabolite urolithins
Phytomedicine ( IF 7.9 ) Pub Date : 2023-05-18 , DOI: 10.1016/j.phymed.2023.154867
Jingyan Li ₁ , Ruixue Liao ₂ , Shijia Zhang ₃ , Huimin Weng ₄ , Yuanzhi Liu ₅ , Tianyi Tao ₆ , Fengxu Yu ₄ , Guang Li ₆ , Jianming Wu ₇

Affiliation

Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China; Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.
Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, China.
Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.
Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China; School of Basic Medical Sciences, Southwest Medical University, Luzhou, China.

Background

Cardiovascular disease (CVD) is a significant worldwide factor contributing to human fatality and morbidity. With the increase of incidence rates, it is of concern that there is a lack of current therapeutic alternatives because of multiple side effects. Ellagic acid (EA), the natural polyphenol (C₁₄H₆O₈), is abundant in pomegranates, berries, and nuts. EA and its intestinal microflora metabolite, urolithins, have recently attracted much attention as a potential novel “medicine” because of their wide pharmacological properties.

Purpose

This study aimed to critically analyze available literature to summarize the beneficial effects of EA and urolithins, and highlights their druggability and therapeutic potential in various CVDs.

Methods

We systematically studied research and review articles between 1984 and 2022 available on various databases to obtain the data on EA and urolithins with no language restriction. Their cardiovascular protective activities, underlying mechanism, and druggability were highlighted and discussed comprehensively.

Results

We found that EA and urolithins may exert preventive and curative effects on CVD with negligible side effects and possibly regulate lipid metabolism imbalance, pro-inflammatory factor production, vascular smooth muscle cell proliferation, cardiomyocyte apoptosis, endothelial cell dysfunction, and Ca²⁺ intake and release. Potentially, this may lead to the prevention and amelioration of atherosclerosis, hypertension, myocardial infarction, cardiac fibrosis, cardiomyopathy, cardiac arrhythmias, and cardiotoxicities in vivo. Several molecules and signaling pathways are associated with their therapeutic actions, including phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, NF-κB, nuclear factor erythroid-2 related factor 2, sirtuin1, miRNA, and extracellular signal-regulated kinase 1/2.

Conclusion

In vitro and in vivo studies shows that EA and urolithins could be used as valid candidates for early prevention and effective therapeutic strategies for various CVDs.

中文翻译：

有望治疗心血管疾病的药物：天然多酚鞣花酸及其代谢物尿石素

背景

心血管疾病 (CVD) 是导致人类死亡和发病的重要全球因素。随着发病率的增加，令人担忧的是，由于多种副作用，目前缺乏治疗选择。鞣花酸 (EA) 是一种天然多酚 (C ₁₄ H ₆ O ₈ )，在石榴、浆果和坚果中含量丰富。EA 及其肠道微生物群代谢物尿石素由于其广泛的药理学特性，最近作为一种潜在的新型“药物”而备受关注。

目的

本研究旨在批判性地分析现有文献以总结 EA 和尿石素的有益作用，并强调它们在各种 CVD 中的成药性和治疗潜力。

方法

我们系统地研究了 1984 年至 2022 年间各种数据库中可用的研究和评论文章，以获得关于 EA 和尿石素的数据，没有语言限制。他们的心血管保护活性、潜在机制和成药性得到了强调和全面讨论。

结果

我们发现 EA 和尿石素可能对 CVD 发挥预防和治疗作用，副作用可忽略不计，并可能调节脂质代谢失衡、促炎因子产生、血管平滑肌细胞增殖、心肌细胞凋亡、内皮细胞功能障碍和 Ca 2+^摄入和发布。潜在地，这可能导致在体内预防和改善动脉粥样硬化、高血压、心肌梗塞、心脏纤维化、心肌病、心律失常和心脏毒性. 一些分子和信号通路与其治疗作用相关，包括磷脂酰肌醇 3-激酶/蛋白激酶 B、丝裂原活化蛋白激酶、NF-κB、核因子 erythroid-2 相关因子 2、sirtuin1、miRNA 和细胞外信号调节激酶 1/2。