{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:09:20Z","timestamp":1791950960807,"version":"4.3.4"},"reference-count":141,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agence Nationale des Plantes M\u00e9dicinales et Aromatiques, Centre National de Recherche Scientifique et Technique, Universit\u00e9 Sultan Moulay Slimane, Morocco","award":["PJT-162366"],"award-info":[{"award-number":["PJT-162366"]}]},{"name":"Canadian Institutes of Health Research","award":["PJT-162366"],"award-info":[{"award-number":["PJT-162366"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Oxidative stress and chronic inflammation, at both the systemic and the central level, are critical early events in atherosclerosis and Alzheimer\u2019s disease (AD). Purpose: To investigate the oxidative stress-, inflammation-, and Tau-phosphorylation-lowering effects of pomegranate polyphenols (PPs) (punicalagin, ellagic acid, peel, and aril extracts). Methods: We used flow cytometry to quantify the protein expression of proinflammatory cytokines (IL-1\u03b2) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1\/M2 cell-specific marker (CD86 and CD163) expression in human microglia HMC3 cells. The IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PPs on human amyloid beta 1-42 (A\u03b21-42)-induced oxidative stress was assessed in the microglia by measuring ROS generation and lipid peroxidation, using 2\u2032,7\u2032-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substance (TBARS) tests, respectively. Neuronal viability and cell apoptotic response to A\u03b21-42 toxicity were assayed using the MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and the annexin-V-FITC apoptosis detection kit, respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PPs to modulate A\u03b21-42-induced Tau-181 phosphorylation (pTau-181). Results: Our data indicate that PPs are significantly (p &lt; 0.05) effective in countering A\u03b21-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) in U373-MG astrocytes and THP1 macrophages and decreasing proinflammatory marker (IL-1\u03b2) expression in THP1 macrophages. The PPs were also significantly (p &lt; 0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p &lt; 0.05) beneficial impact on oxidative stress, illustrated in the reduction in TBARS and ROS generation. Our treatments have significant (p &lt; 0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that A\u03b21-42 significantly (p &lt; 0.05) increases pTau-181. This effect is significantly (p &lt; 0.05) attenuated by arils, peels, and punicalagin and drastically reduced by the ellagic acid treatment. Conclusion: Overall, our results attribute to PPs anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau-pathology potential. Future studies should aim to extend our knowledge of the potential role of PPs in A\u03b21-42-induced neurodegeneration, particularly concerning its association with the tauopathy involved in AD.<\/jats:p>","DOI":"10.3390\/nu16213667","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T11:52:47Z","timestamp":1730116367000},"page":"3667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["In Vitro Assessment of the Neuroprotective Effects of Pomegranate (Punica granatum L.) Polyphenols Against Tau Phosphorylation, Neuroinflammation, and Oxidative Stress"],"prefix":"10.3390","volume":"16","author":[{"given":"Mehdi","family":"Alami","sequence":"first","affiliation":[{"name":"Department of Biology, Polydisciplinary Faculty, University Sultan Moulay Slimane, Beni Mellal 23020, Morocco"},{"name":"Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 4N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoutar","family":"Boumezough","sequence":"additional","affiliation":[{"name":"Department of Biology, Polydisciplinary Faculty, University Sultan Moulay Slimane, Beni Mellal 23020, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Echarki","family":"Zerif","sequence":"additional","affiliation":[{"name":"Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 4N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Zoubdane","sequence":"additional","affiliation":[{"name":"Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 4N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0817-3160","authenticated-orcid":false,"given":"Abdelouahed","family":"Khalil","sequence":"additional","affiliation":[{"name":"Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 4N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7659-3162","authenticated-orcid":false,"given":"Ton","family":"Bunt","sequence":"additional","affiliation":[{"name":"Izumi Biosciences, Inc., Lexington, MA 02420, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4032-3213","authenticated-orcid":false,"given":"Benoit","family":"Laurent","sequence":"additional","affiliation":[{"name":"Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 4N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-1109","authenticated-orcid":false,"given":"Jacek","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Department of Embryology, Medical University of Gdansk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Ramassamy","sequence":"additional","affiliation":[{"name":"INRS-Centre Armand-Frappier Sant\u00e9 Biotechnologie, Laval, QC H7V 1B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Boulbaroud","sequence":"additional","affiliation":[{"name":"Department of Biology, Polydisciplinary Faculty, University Sultan Moulay Slimane, Beni Mellal 23020, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamas","family":"Fulop","sequence":"additional","affiliation":[{"name":"Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 4N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0546-6534","authenticated-orcid":false,"given":"Hicham","family":"Berrougui","sequence":"additional","affiliation":[{"name":"Department of Biology, Polydisciplinary Faculty, University Sultan Moulay Slimane, Beni Mellal 23020, Morocco"},{"name":"Research Center on Aging, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC J1H 4N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0197-4580(88)80079-4","article-title":"Expression of Immune System-Associated Antigens by Cells of the Human Central Nervous System: Relationship to the Pathology of Alzheimer\u2019s Disease","volume":"9","author":"Rogers","year":"1988","journal-title":"Neurobiol. 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