Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer’s Disease through ApoE4/LRP1, Wnt3/β-Catenin/GSK3β, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model

Hamdan, Ahmed M.; Alharthi, Fatimah; Alanazi, Ahmed Hadi; El-Emam, Soad Z.; Zaghlool, Sameh S.; Metwally, Kamel; Albalawi, Sana Abdulaziz; Abdu, Yahia S.; Mansour, Reda E.; Salem, Hoda A.; Elmageed, Zakaria Y. Abd; Abu-Elfotuh, Karema

doi:10.3390/ph15081008

Cited by 20 publications

(29 citation statements)

References 92 publications

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“…Aluminum is a neurotoxic agent that causes oxidative stress ( 7 ). It is known to cause toxic effects on various systems, including the brain, bone, Kidney, and blood ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Allium sativum and Nigella sativa on alleviating aluminum toxicity state in the albino rats

et al. 2022

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The study objective was to evaluate Allium sativum's potential and Nigella Sativa's combination's potential to reduce aluminum toxicity and return to the normal state. In the present study, a hundred albino rats were randomly divided into five equal groups. The first group was used as a control group; the other four groups were exposed to aluminum 1,600 ppm. The second exposed to aluminum only; the third and fourth groups were treated with Allium sativum 5% and Nigella sativa 5%, respectively, while the fifth group was treated with a mix of Allium sativum 2.5% and Nigella sativa 2.5% for 8th weeks. After 8 weeks, the aluminum administration was stopped, and the second group was divided into three groups. The groups were treated with Allium sativum 5% and Nigella sativa 5%, and a mix of Allium sativum 2.5% and Nigella sativa 2.5%, respectively. The first group was the control group (continued from the first experiment). Garlic and Nigella sativa were crushed and added to feed while receiving aluminum chloride daily at a dose of 1.6 ml/l was added to the drinking water. Histopathological changes in the liver, kidney, and testes were investigated after 8 and 16 weeks, and blood samples were collected after 4, 8, and 16 weeks for biochemical blood parameters. The results showed that the histopathological examination of the liver, kidney, and testes showed signs of congestion in blood vessels after aluminum exposure. Meanwhile, the treatment with Allium sativum or Nigella sativum or the mixture between them had positive effects on evading the harmful effects of aluminum in the liver, Kidney, and testes tissues. In addition, there were protective effects for Allium sativum and Nigella sativa against aluminum on serum creatinine, urea, ALT, and AST concentrations. The present study concluded that supplementation with Allium sativum or Nigella sativa or their combination could reduce aluminum toxicity and return the liver, kidney, and testes to normal.

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“…Aluminum is a neurotoxic agent that causes oxidative stress ( 7 ). It is known to cause toxic effects on various systems, including the brain, bone, Kidney, and blood ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of Allium sativum and Nigella sativa on alleviating aluminum toxicity state in the albino rats

et al. 2022

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“…Neurodegenerative disease progression has been extensively shown to be influenced by oxidative stress, inflammation, and apoptosis (Behl et al, 2021;Merelli et al, 2021;Zarneshan et al, 2022). In this regard, previous studies indicated that Al exposure can induce various neurological disorders (Aly et al, 2011;Hamdan et al, 2022;Turkez et al, 2022). Therefore, chronic exposure to Al in mouse models has frequently been used as an experimental model of neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Suppressed cholinergic transmission was reported to activate the inflammatory system by increasing N-methyl-D-aspartate receptor expression, disrupting cognition, and increasing neurotoxicity ( Haider et al, 2020 ; Amanzadeh Jajin et al, 2021 ; Firdaus et al, 2022 ). AlCl3 may cause neurodegeneration through multiple interlocking pathogenic pathways ( Wang et al, 2019 ; Shunan et al, 2021 ; Hamdan et al, 2022 ). However, one of the reasons that IMP is effective against Al-induced neurotoxicity is probably due to its anti-inflammatory action on cytokines and its role in normalizing ACh levels in the brain.…”

Section: Discussionmentioning

confidence: 99%

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Isoimperatorin therapeutic effect against aluminum induced neurotoxicity in albino mice

Rajendran

Althumairy

Banl-Ismail³

et al. 2023

Front. Pharmacol.

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Background: Although aluminum (Al) is not biologically crucial to the human body, classical studies have demonstrated that excessive human exposure to Al can induce oxidative damage, neuroinflammatory conditions and neurotoxic manifestations implicated in Alzheimer’s disease (AD). Exposure to Al was reported to be associated with oxidative damage, neuroinflammation, and to enhance progressive multiregional neurodegeneration in animal models. Several plant-derived natural biomolecules have been recently used to reduce the toxic effects of Al through decreasing the oxidative stress and the associated diseases. A good candidate still to be tested is an active natural furanocoumarin, the isoimperatorin (IMP) that can be extracted from Lemon and lime oils and other plants. Here, we examined the neuroprotective effects of IMP on aluminum chloride (AlCl3)-induced neurotoxicity in albino mice.Methods: Twenty-four male albino mice were used in this study. Mice were randomly devided into 5 groups. The first group was given distilled water as a control, the second group was given AlCl3 orally (10 mg/wt/day) starting from the 2nd week to the end of the 6th week, the third group received AlCl3 orally and IMP interperitoneally, i. p. (30 mg/wt/day) starting from week 2 till week 6 where IMP was supplement 1st and then 4 h later AlCl3 was given to mice. The fourth group received the control (IMP 30 mg/wt, i. p.) from the 2nd week till the end of the experiment. Rodent models of central nervous system (CNS) disorders were assessed using object location memory and Y-maze tests in 6th week began. Essential anti-inflammatory and oxidative stress indicators were evaluated, including interleukin-1 β (IL-1β), tumor necrosis factor α (TNF-α), malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity (CAT). In addition, serum levels of brain neurotransmitters such as corticosterone, acetylcholine (ACh), dopamine and serotonin in brain homogenates were measured calorimetrically.Results: The study results revealed that the daily treatment of AlCl3 upregulated the TNF-α and IL-1β levels, increased MDA accumulation, and decreased TAC and CAT activity. In addition, aluminum induced a reduction in concentrations of ACh, serotonin and dopamine in the brain. However, IMP significantly ameliorates the effect of AlCl3 through modulating the antioxidant and regulating the inflammatory response through targeting Nrf2 (NF-E2-related factor 2) and mitogen-activated protein kinase (MAPK).Conclusion: Thus, IMP might be a promising treatment option for neurotoxicity and neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, which are associated with neuro-inflammation and oxidative stress.

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“…Based on these premises, Hamdan et al [ 26 ] carried out a study on the neuroprotective activity of some phytochemicals such as morin, thymol, and thymoquinone in the absence/presence of physical and mental activities in a rat model of AD induced by aluminum chloride (AlCl 3 ). AlCl 3 led to a decline in spatial learning and memory, inducing histopathological changes in rat brains.…”

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confidence: 99%

Neuroprotection by Drugs, Nutraceuticals and Physical Activity

Tarozzi

Angeloni

2023

IJMS

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Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer’s Disease through ApoE4/LRP1, Wnt3/β-Catenin/GSK3β, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model

Cited by 20 publications

References 92 publications

Effect of Allium sativum and Nigella sativa on alleviating aluminum toxicity state in the albino rats

Effect of Allium sativum and Nigella sativa on alleviating aluminum toxicity state in the albino rats

Isoimperatorin therapeutic effect against aluminum induced neurotoxicity in albino mice

Neuroprotection by Drugs, Nutraceuticals and Physical Activity

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