Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential

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Abstract

Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate ( Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.

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Oxidative stress and diabetic complications.

Ferdinando Giacco, Michael Brownlee, Ann Marie Schmidt (2010)

Oxidative stress plays a pivotal role in the development of diabetes complications, both microvascular and cardiovascular. The metabolic abnormalities of diabetes cause mitochondrial superoxide overproduction in endothelial cells of both large and small vessels, as well as in the myocardium. This increased superoxide production causes the activation of 5 major pathways involved in the pathogenesis of complications: polyol pathway flux, increased formation of AGEs (advanced glycation end products), increased expression of the receptor for AGEs and its activating ligands, activation of protein kinase C isoforms, and overactivity of the hexosamine pathway. It also directly inactivates 2 critical antiatherosclerotic enzymes, endothelial nitric oxide synthase and prostacyclin synthase. Through these pathways, increased intracellular reactive oxygen species (ROS) cause defective angiogenesis in response to ischemia, activate a number of proinflammatory pathways, and cause long-lasting epigenetic changes that drive persistent expression of proinflammatory genes after glycemia is normalized ("hyperglycemic memory"). Atherosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS. Overexpression of superoxide dismutase in transgenic diabetic mice prevents diabetic retinopathy, nephropathy, and cardiomyopathy. The aim of this review is to highlight advances in understanding the role of metabolite-generated ROS in the development of diabetic complications.

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Plant polyphenols as dietary antioxidants in human health and disease

Kanti Bhooshan Pandey, Syed Ibrahim Rizvi (2009)

Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.

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Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients.

L Bubendorf, A Schöpfer, U. Wagner … (2000)

The prognosis of prostate cancer is mainly determined by the presence or absence of metastases. Nevertheless, the metastatic pathways in prostate cancer are not entirely understood. Among 19,316 routine autopsies performed from 1967 to 1995 on men older than 40 years of age, the reports from those 1,589 (8.2%) with prostate cancer were analyzed. Hematogeneous metastases were present in 35% of 1,589 patients with prostate cancer, with most frequent involvement being bone (90%), lung (46%), liver (25%), pleura (21%), and adrenals (13%). Several lines of evidence suggested the existence of a backward metastatic pathway through veins from the prostate to the spine in addition to classical hematogeneous tumor spread via the vena cava. First, there was an inverse relationship between spine and lung metastases, suggesting that metastasis to the spine is independent of lung metastasis. Second, the maximum frequency of spine involvement occurred in smaller tumors (4 to 6 cm) as compared with the maximum spread to lung (6 to 8 cm) and liver (>8 cm), suggesting that spine metastases precede lung and liver metastases in many prostate cancers. Third, there was a gradual decrease in spine involvement from the lumbar to the cervical level (97% v 38%), which is consistent with a subsequent upward metastatic spread along spinal veins after initial lumbar metastasis. The results of this study show that bone, lung, and liver are the most frequent sites of distant prostate cancer metastases. Besides the cava-type of metastasis through lung passage, there are strong arguments for the existence and clinical significance of a backward venous spread to the spine, which is likely to occur early in the metastatic process.

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Author and article information

Contributors

Javad Sharifi-Rad:

ORCID: https://orcid.org/0000-0002-7301-8151

Daniela Rigano:

ORCID: https://orcid.org/0000-0002-9176-8044

Michael Wink:

ORCID: https://orcid.org/0000-0002-7875-4510

William C. Cho:

ORCID: https://orcid.org/0000-0003-4174-4586

Journal

Journal ID (nlm-ta): Oxid Med Cell Longev

Journal ID (iso-abbrev): Oxid Med Cell Longev

Journal ID (publisher-id): OMCL

Title: Oxidative Medicine and Cellular Longevity

Publisher: Hindawi

ISSN (Print): 1942-0900

ISSN (Electronic): 1942-0994

Publication date Collection: 2022

Publication date (Electronic): 21 February 2022

Volume: 2022

Electronic Location Identifier: 3848084

Affiliations

¹Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador

²Facultad de Ciencias de la Salud, Universidad Arturo Prat, Avda. Arturo Prat 2120, Iquique 1110939, Chile

³Biotechnology and Genetic Engineering Group, Science and Technology Faculty, Universidad del Azuay, Av. 24 de Mayo 7-77, Cuenca, Ecuador

⁴Universidad del Azuay, Grupos Estratégicos de Investigación en Ciencia y Tecnología de Alimentos y Nutrición Industrial (GEICA-UDA), Av. 24 de Mayo 7-77, Apartado 01.01.981, Cuenca, Ecuador

⁵Ivan Franko National University of Lviv, Lviv, Ukraine

⁶Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

⁷National Research Council (CNR), Institute of Biosciences and Bioresources (IBBR), Via Università 133, 80055 Portici, Naples, Italy

⁸Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Via L. De Crecchio 7, 80138 Naples, Italy

⁹Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, 4070386 Concepción, Chile

¹⁰Department of Biology, Faculty of Science, Sivas Cumhuriyet University, 58140 Sivas, Turkey

¹¹Beekeeping Development Application and Research Center, Sivas Cumhuriyet University, 58140 Sivas, Turkey

¹²Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano, 49 80131 Naples, Italy

¹³Heidelberg University, Institute of Pharmacy and Molecular Biotechnology, INF 329, D-69120 Heidelberg, Germany

¹⁴Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong

Author notes

Academic Editor: Lei Chen

Author information

Javad Sharifi-Rad https://orcid.org/0000-0002-7301-8151

Luigi De Masi https://orcid.org/0000-0002-0460-7040

Miquel Martorell https://orcid.org/0000-0003-3183-7623

Daniela Rigano https://orcid.org/0000-0002-9176-8044

Michael Wink https://orcid.org/0000-0002-7875-4510

William C. Cho https://orcid.org/0000-0003-4174-4586

Article

DOI: 10.1155/2022/3848084

PMC ID: 8885183

PubMed ID: 35237379

SO-VID: 4f4a07da-d8d9-4089-bd2e-625051705e40

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 11 October 2021

Date accepted : 31 January 2022

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Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential

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Most cited references 304

Oxidative stress and diabetic complications.

Plant polyphenols as dietary antioxidants in human health and disease

Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients.

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Cited by 44