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

Jingyan Li; Ruixue Liao; Shijia Zhang; Huimin Weng; Yuanzhi Liu; Tianyi Tao; Fengxu Yu; Guang Li; Jianming Wu

doi:10.1016/j.phymed.2023.154867

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

Phytomedicine. 2023 Jul 25:116:154867. doi: 10.1016/j.phymed.2023.154867. Epub 2023 May 18.

Authors

Jingyan Li¹, Ruixue Liao², Shijia Zhang³, Huimin Weng⁴, Yuanzhi Liu⁵, Tianyi Tao⁶, Fengxu Yu⁷, Guang Li⁸, Jianming Wu⁹

Affiliations

¹ 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.
² 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.
³ School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, China.
⁴ Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
⁵ 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.
⁶ 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.
⁷ Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China. Electronic address: yuluchuan@163.com.
⁸ 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. Electronic address: liguang@swmu.edu.cn.
⁹ 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. Electronic address: jianmingwu@swmu.edu.cn.

PMID: 37257327
DOI: 10.1016/j.phymed.2023.154867

Abstract

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.

Keywords: Atherosclerosis; Cardiomyopathy; Cardiotoxicity; Ellagic acid; Heart disease; Urolithin.

Publication types

Review

MeSH terms

Cardiovascular Diseases* / drug therapy
Coumarins / pharmacology
Ellagic Acid / pharmacology
Gastrointestinal Microbiome*
Humans
Lipid Metabolism
Polyphenols / pharmacology

Substances

Ellagic Acid
Polyphenols
Coumarins