In Vitro Assessment of the Neuroprotective Effects of Pomegranate (Punica granatum L.) Polyphenols Against Tau Phosphorylation, Neuroinflammation, and Oxidative Stress

Alami, Mehdi; Boumezough, Kaoutar; Zerif, Echarki; Zoubdane, Nada; Khalil, Abdelouahed; Bunt, Ton; Laurent, Benoit; Witkowski, Jacek M; Ramassamy, Charles ORCID: https://orcid.org/0000-0002-3252-5878; Boulbaroud, Samira; Fulop, Tamas et Berrougui, Hicham (2024). In Vitro Assessment of the Neuroprotective Effects of Pomegranate (Punica granatum L.) Polyphenols Against Tau Phosphorylation, Neuroinflammation, and Oxidative Stress Nutrients , vol. 16 , nº 21. pp. 1-30. DOI: 10.3390/nu16213667.

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Résumé

Background: Oxidative stress and chronic inflammation, at both the systemic and the central level, are critical early events in atherosclerosis and Alzheimer’s 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-1β) 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 (Aβ1-42)-induced oxidative stress was assessed in the microglia by measuring ROS generation and lipid peroxidation, using 2′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substance (TBARS) tests, respectively. Neuronal viability and cell apoptotic response to Aβ1-42 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 Aβ1-42-induced Tau-181 phosphorylation (pTau-181). Results: Our data indicate that PPs are significantly (p < 0.05) effective in countering Aβ1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) in U373-MG astrocytes and THP1 macrophages and decreasing proinflammatory marker (IL-1β) expression in THP1 macrophages. The PPs were also significantly (p < 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 < 0.05) beneficial impact on oxidative stress, illustrated in the reduction in TBARS and ROS generation. Our treatments have significant (p < 0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ1-42 significantly (p < 0.05) increases pTau-181. This effect is significantly (p < 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 Aβ1-42-induced neurodegeneration, particularly concerning its association with the tauopathy involved in AD.

Type de document:	Article
Mots-clés libres:	Neuroinflammation; Alzheimer’s disease; pomegranate (Punica granatum L.); oxidative stress; microglia; amyloid-beta; phospho-Tau-181; ellagic acid; punicalagin
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	18 nov. 2024 06:17
Dernière modification:	18 nov. 2024 06:17
URI:	https://espace.inrs.ca/id/eprint/16168

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