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Immunomodulatory Activity of Punicalagin, Punicalin, and Ellagic Acid Differs from the Effect of Pomegranate Peel Extract

Background: Our recent study has shown that pomegranate peel extract (PEx) showed significant immunomodulatory activity, which might be caused by ellagitannins. The aim of this work was to test the hypothesis that ellagitannin components act synergistically in the modulation of cytokine production....

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Autores principales: Čolić, Miodrag, Mihajlović, Dušan, Bekić, Marina, Marković, Milan, Dragišić, Branka, Tomić, Sergej, Miljuš, Nataša, Šavikin, Katarina, Škrbić, Ranko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695876/
https://www.ncbi.nlm.nih.gov/pubmed/36431972
http://dx.doi.org/10.3390/molecules27227871
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author Čolić, Miodrag
Mihajlović, Dušan
Bekić, Marina
Marković, Milan
Dragišić, Branka
Tomić, Sergej
Miljuš, Nataša
Šavikin, Katarina
Škrbić, Ranko
author_facet Čolić, Miodrag
Mihajlović, Dušan
Bekić, Marina
Marković, Milan
Dragišić, Branka
Tomić, Sergej
Miljuš, Nataša
Šavikin, Katarina
Škrbić, Ranko
author_sort Čolić, Miodrag
collection PubMed
description Background: Our recent study has shown that pomegranate peel extract (PEx) showed significant immunomodulatory activity, which might be caused by ellagitannins. The aim of this work was to test the hypothesis that ellagitannin components act synergistically in the modulation of cytokine production. Methods: Human peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with phytohemagglutinin and treated with different concentrations of PEx or punicalagin (PG), punicalin (PN), and ellagic acid (EA), alone or with their combinations. Cytotoxicity, cell proliferation, and cytokine production were determined. Results: Non-cytotoxic concentrations of all compounds significantly inhibited cell proliferation. IC50 values (μg/mL) were: EA (7.56), PG (38.52), PEx (49.05), and PN (69.95). PEx and all ellagitannins inhibited the levels of TNF-α, IL-6, and IL-8, dose-dependently, and their combinations acted synergistically. PEx and all ellagitannins inhibited Th1 and Th17 responses, whereas the lower concentrations of PEx stimulated the production of IL-10, a Treg cytokine, as did lower concentrations of EA. However, neither component of ellagitannins increased Th2 response, as was observed with PEx. Conclusions: The combination of PG, PN, and EA potentiated the anti-inflammatory response without any significant synergistic down-modulatory effect on T-cell cytokines. The increased production of IL-10 observed with PEx could be attributable to EA, but the examined ellagitannins are not associated with the stimulatory effect of PEx on Th2 response.
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spelling pubmed-96958762022-11-26 Immunomodulatory Activity of Punicalagin, Punicalin, and Ellagic Acid Differs from the Effect of Pomegranate Peel Extract Čolić, Miodrag Mihajlović, Dušan Bekić, Marina Marković, Milan Dragišić, Branka Tomić, Sergej Miljuš, Nataša Šavikin, Katarina Škrbić, Ranko Molecules Article Background: Our recent study has shown that pomegranate peel extract (PEx) showed significant immunomodulatory activity, which might be caused by ellagitannins. The aim of this work was to test the hypothesis that ellagitannin components act synergistically in the modulation of cytokine production. Methods: Human peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with phytohemagglutinin and treated with different concentrations of PEx or punicalagin (PG), punicalin (PN), and ellagic acid (EA), alone or with their combinations. Cytotoxicity, cell proliferation, and cytokine production were determined. Results: Non-cytotoxic concentrations of all compounds significantly inhibited cell proliferation. IC50 values (μg/mL) were: EA (7.56), PG (38.52), PEx (49.05), and PN (69.95). PEx and all ellagitannins inhibited the levels of TNF-α, IL-6, and IL-8, dose-dependently, and their combinations acted synergistically. PEx and all ellagitannins inhibited Th1 and Th17 responses, whereas the lower concentrations of PEx stimulated the production of IL-10, a Treg cytokine, as did lower concentrations of EA. However, neither component of ellagitannins increased Th2 response, as was observed with PEx. Conclusions: The combination of PG, PN, and EA potentiated the anti-inflammatory response without any significant synergistic down-modulatory effect on T-cell cytokines. The increased production of IL-10 observed with PEx could be attributable to EA, but the examined ellagitannins are not associated with the stimulatory effect of PEx on Th2 response. MDPI 2022-11-15 /pmc/articles/PMC9695876/ /pubmed/36431972 http://dx.doi.org/10.3390/molecules27227871 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Čolić, Miodrag
Mihajlović, Dušan
Bekić, Marina
Marković, Milan
Dragišić, Branka
Tomić, Sergej
Miljuš, Nataša
Šavikin, Katarina
Škrbić, Ranko
Immunomodulatory Activity of Punicalagin, Punicalin, and Ellagic Acid Differs from the Effect of Pomegranate Peel Extract
title Immunomodulatory Activity of Punicalagin, Punicalin, and Ellagic Acid Differs from the Effect of Pomegranate Peel Extract
title_full Immunomodulatory Activity of Punicalagin, Punicalin, and Ellagic Acid Differs from the Effect of Pomegranate Peel Extract
title_fullStr Immunomodulatory Activity of Punicalagin, Punicalin, and Ellagic Acid Differs from the Effect of Pomegranate Peel Extract
title_full_unstemmed Immunomodulatory Activity of Punicalagin, Punicalin, and Ellagic Acid Differs from the Effect of Pomegranate Peel Extract
title_short Immunomodulatory Activity of Punicalagin, Punicalin, and Ellagic Acid Differs from the Effect of Pomegranate Peel Extract
title_sort immunomodulatory activity of punicalagin, punicalin, and ellagic acid differs from the effect of pomegranate peel extract
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695876/
https://www.ncbi.nlm.nih.gov/pubmed/36431972
http://dx.doi.org/10.3390/molecules27227871
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