Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways
Alzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in a...
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MDPI AG
2023-07-01
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| author | Karema Abu-Elfotuh Amina M. A. Tolba Furqan H. Hussein Ahmed M. E. Hamdan Mohamed A. Rabeh Saad A. Alshahri Azza A. Ali Sarah M. Mosaad Nihal A. Mahmoud Magdy Y. Elsaeed Ranya M. Abdelglil Rehab R. El-Awady Eman Reda M. Galal Mona M. Kamal Ahmed M. M. Elsisi Alshaymaa Darwish Ayah M. H. Gowifel Yasmen F. Mahran |
| author_facet | Karema Abu-Elfotuh Amina M. A. Tolba Furqan H. Hussein Ahmed M. E. Hamdan Mohamed A. Rabeh Saad A. Alshahri Azza A. Ali Sarah M. Mosaad Nihal A. Mahmoud Magdy Y. Elsaeed Ranya M. Abdelglil Rehab R. El-Awady Eman Reda M. Galal Mona M. Kamal Ahmed M. M. Elsisi Alshaymaa Darwish Ayah M. H. Gowifel Yasmen F. Mahran |
| author_sort | Karema Abu-Elfotuh |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl<sub>3</sub>) alone, AlCl<sub>3</sub> with cocoa alone, AlCl<sub>3</sub> with vinpocetine (VIN), AlCl<sub>3</sub> with epigallocatechin-3-gallate (EGCG), AlCl<sub>3</sub> with coenzyme Q10 (CoQ10), AlCl<sub>3</sub> with wheatgrass (WG), AlCl<sub>3</sub> with vitamin (Vit) B complex, and AlCl<sub>3</sub> with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl<sub>3</sub> administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl<sub>3</sub> intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl<sub>3</sub>-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways. |
| first_indexed | 2024-03-10T23:39:58Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T23:39:58Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj.art-d3b8baac599947bc8f2ff37ee26be73b2023-11-19T02:36:12ZengMDPI AGPharmaceutics1999-49232023-07-01158206310.3390/pharmaceutics15082063Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 PathwaysKarema Abu-Elfotuh0Amina M. A. Tolba1Furqan H. Hussein2Ahmed M. E. Hamdan3Mohamed A. Rabeh4Saad A. Alshahri5Azza A. Ali6Sarah M. Mosaad7Nihal A. Mahmoud8Magdy Y. Elsaeed9Ranya M. Abdelglil10Rehab R. El-Awady11Eman Reda M. Galal12Mona M. Kamal13Ahmed M. M. Elsisi14Alshaymaa Darwish15Ayah M. H. Gowifel16Yasmen F. Mahran17Clinical Pharmacy Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11651, EgyptAnatomy Department, Faculty of Medicine, Girls Branch, Al-Azhar University, Cairo 11651, EgyptCollege of Dentistry, University of Alkafeel, Najaf 54001, IraqDepartment of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62521, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62521, Saudi ArabiaPharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11651, EgyptResearch Unit, Egypt Healthcare Authority, Ismailia Branch, Ismailia 41522, EgyptPhysiology Department, Faculty of Medicine (Girls), Al-Azhar University, Cairo 11651, EgyptPhysiology Department, Faculty of Medicine (Boys), Al-Azhar University, Demietta 34517, EgyptDepartment of Anatomy and Embryology, Faculty of Medicine (Girls), Al-Azhar University, Cairo 11651, EgyptBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11651, EgyptBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11651, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11651, EgyptBiochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11651, EgyptBiochemistry Department, Faculty of Pharmacy, Sohag University, Sohag 82524, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo 11571, EgyptPharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, EgyptAlzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl<sub>3</sub>) alone, AlCl<sub>3</sub> with cocoa alone, AlCl<sub>3</sub> with vinpocetine (VIN), AlCl<sub>3</sub> with epigallocatechin-3-gallate (EGCG), AlCl<sub>3</sub> with coenzyme Q10 (CoQ10), AlCl<sub>3</sub> with wheatgrass (WG), AlCl<sub>3</sub> with vitamin (Vit) B complex, and AlCl<sub>3</sub> with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl<sub>3</sub> administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl<sub>3</sub> intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl<sub>3</sub>-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways.https://www.mdpi.com/1999-4923/15/8/2063Alzheimer’s diseaseGSK-3β-Wnt/β-cateninPERK/CHOP/Bcl-2oxidative stresscocoavinpocetine |
| spellingShingle | Karema Abu-Elfotuh Amina M. A. Tolba Furqan H. Hussein Ahmed M. E. Hamdan Mohamed A. Rabeh Saad A. Alshahri Azza A. Ali Sarah M. Mosaad Nihal A. Mahmoud Magdy Y. Elsaeed Ranya M. Abdelglil Rehab R. El-Awady Eman Reda M. Galal Mona M. Kamal Ahmed M. M. Elsisi Alshaymaa Darwish Ayah M. H. Gowifel Yasmen F. Mahran Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways Pharmaceutics Alzheimer’s disease GSK-3β-Wnt/β-catenin PERK/CHOP/Bcl-2 oxidative stress cocoa vinpocetine |
| title | Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways |
| title_full | Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways |
| title_fullStr | Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways |
| title_full_unstemmed | Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways |
| title_short | Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways |
| title_sort | anti alzheimer activity of combinations of cocoa with vinpocetine or other nutraceuticals in rat model modulation of wnt3 β catenin gsk 3β nrf2 ho 1 and perk chop bcl 2 pathways |
| topic | Alzheimer’s disease GSK-3β-Wnt/β-catenin PERK/CHOP/Bcl-2 oxidative stress cocoa vinpocetine |
| url | https://www.mdpi.com/1999-4923/15/8/2063 |
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