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Aluminium (Al) is a potent neurotoxic metal known to cause neurodegeneration. Al exposure causes oxidative stress by accumulation of reactive oxygen species, followed by the activation of neuronal cell death in the brain. Asiatic acid (AA), the major bioactive compound of Centella asiatica (a medicinal plant), act as multifunctional drug as well as an antioxidant. Thus, the present study aimed to investigate the potential neuroprotective effect of AA against Al neurotoxicity. Rats were orally administered aluminium chloride (AlCl 3 ; 100 mg/kg b. wt.) dissolved in distilled water for 8 weeks or AA (75 mg/kg b. wt.) in combination with AlCl 3 . The results showed that AlCl 3 -intoxication causes significant impairment of memory, enhances anxiety-like behavior, acetyl cholinesterase (AChE) activity, malondialdehydes (MDA) level, and concomitant decrease in the activities of superoxide dismutase (SOD) and catalase (CAT) in the cortex and hippocampus regions of rat brain. In addition, AlCl 3 -intoxication enhanced neuronal loss and reactive astrogliosis in both regions. However, co-administration of AA with AlCl 3 significantly attenuated the behavioral alterations, restored SOD and CAT activities, while reduced AChE activity and MDA content. Further, the study demonstrated that AA attenuates neuronal loss and reactive astrogliosis in rat brain. In conclusion, the study suggests that AA protects rat brain from Al neurotoxicity by inhibiting oxidative stress, neuronal loss and reactive astrogliosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Amyloid-β (Aβ) peptides play a key role in Alzheimer's disease (AD), the most common type of dementia. In this study, a polysaccharide from Bletilla striata (BSP), with strong antioxidant and anti-inflammatory properties, was extracted using a low-temperature method and tested for its efficacy against AD, in vitro using N2a and BV-2 cells, and in vivo using an AD rat model. The characterization of the extracted BSP for its molecular structure and functional groups demonstrated the effectiveness of the modified method for retaining its bioactivity. In vitro, BSP reduced by 20% reactive oxygen species (ROS) levels in N2a cells ( p = 0.0082) and the expression levels of inflammation-related genes by 3-fold TNF-α ( p = 0.0048), 4-fold IL-6 ( p = 0.0019), and 2.5-fold IL-10 ( p = 0.0212) in BV-2 cells treated with Aβ fibrils. In vivo, BSP recovered learning memory, ameliorated morphological damage in the hippocampus and cortex, and reduced the expression of the β-secretase protein in AlCl 3 -induced AD rats. Collectively, these findings demonstrated the efficacy of BSP for preventing and alleviating the effects of AD.

Background: Aluminum toxicity induces neurodegenerative changes in the brain and results in Alzheimer's disease (AD)., Objective: Here, the aim was to evaluate the antioxidant therapeutic effects of ellagic acid (EA) and EA-loaded nanoparticles (EA-NP) in an aluminum chloride-induced AD rat model., Methods: The nanoparticles' loading of EA was 0.84/1 w/w. The in vitro release kinetics of EA from EA-NP in fetal bovine serum showed 60% release in the first 1-5 hours, followed by sustained release at 60-70% over 6-24 hours. Six groups were implemented; group 1 served as the control, group 2 received EA, group 3 received EA-NP, group 4 was the AD rat model administered AlCl3 (50 mg/kg) for 4 weeks, groups 5 (AD+EA) and 6 (AD+EA-NP) were treated with EA and EA-NP, respectively, for 2 weeks after AlCl3 was stopped. The neurotoxicity in the rat brain was examined by measuring the brain antioxidant biomarkers catalase, glutathione, and total antioxidant activity and lipid peroxidation (thiobarbituric acid, TBA). Histopathological studies using hematoxylin and eosin, cresyl violet, silver stains, and the novel object recognition test were examined., Results: Data revealed significant increase of antioxidant biomarkers and decreased TBA in the EA-NP group. The pathological hallmarks of AD-vacuolation of the neurons, chromatolysis, neurofibrillary tangles, and the senile plaques in brains of the AD rat model were decreased and restoration of Nissl granules was noted. The calculated discrimination index in the behavioral test increased more in cases treated with EA-NP., Conclusion: The treatment of AD with EA-NP was more effective than EA in alleviating the oxidative neurotoxic effects on AD rat brains., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Accumulation of aluminium (Al) in the brain is known to be a toxic insult that result in neurodegenerative diseases and melatonin is known to have neuroprotective role. The present study was designed to investigate the neuroprotective effects of melatonin for aluminium chloride (AlCl 3 )-induced neurotoxicity in rats. Twelve-week old male Wistar rats were orally received 175 mg/kg AlCl 3 with or without 5 mg/kg melatonin intraperitoneal pretreatment. Group 3 intraperitoneally recieved 5 mg/kg melatonin and group 4 rats were orally treated with saline solution for 8 weeks. A series of behavioral tests, biochemical analysis and expression of AD-associated proteins in the brain were determined after 7 weeks of all treatments. Our results indicated that AlCl 3 treatment tends to induce memory and cognitive impairment. However, melatonin treatment attenuated amyloid beta (Aβ) (1-42) level by decreasing β-secretase, augmented low-density lipoprotein receptor-related protein 1, and neprilysin protein expression. Moreover, AlCl 3 -induced endoplasmic reticulum (ER) stress and oxidative stress was attenuated by melatonin supplementation. In conclusion, these findings demonstrate a protective role of melatonin against Aβ peptide accumulation, ER stress and oxidative stress in the AlCl 3 -treated AD model. Hence, the melatonin supplement might be an alternative way to alleviate the development of AD., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A large number of studies showed that aluminum (Al) has potential neurotoxicity to human and animal bodies. Al-treated animals showed anxiety-like behavior, oxidative stress, neuroinflammation and γ-aminobutyric acid (GABA) changes. Bergamot essential oil (BEO) is a kind of well-known plant extract from the fresh fruit of bergamot. Previous studies suggested that BEO improved mood and relieved symptoms of stress-induced anxiety. This study was designed to study the effects of BEO on anxiety-like behavior, oxidative stress, neuroinflammation and GABA system in aluminum trichloride (AlCl 3 ) treated rats. Results showed that AlCl 3 exposure induced anxiety-like behavior in the elevated plus maze and the open field test. Moreover, AlCl 3 exposure decreased the level of GABA and the activity of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in the hippocampus (HP) and the frontal cortex (FC). In addition, AlCl 3 exposure increased the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the HP and the FC. To the contrary, co-administration of BEO and AlCl 3 improved the anxiety-like behavior, GABA system, oxidative stress and neuroinflammation. These results indicated that BEO can alleviate the anxiety-like behavior of AlCl 3 -exposed rats through the combined action of antioxidant, anti-inflammatory and GABA regulation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aluminum is a potent neurotoxin used in animal models of neurodegenerative diseases like Alzheimer's disease (AD), in which oxidative stress mediates tissue pathogenesis in vivo. N-acetyl cysteine (NAC) is a glutathione precursor with reported antioxidant and neuroprotective potentials. Recent therapy for combating AD is known to provide only symptomatic relief thus necessitating the discovery of new drugs and their mechanism of action. This study was aimed to demonstrate the in vivo neuroprotective effect of NAC against aluminum (Al 3+ )-induced neuro-degeneration in rats (a model for AD). Twenty- five (25) adult male Wistar rats used for this study were divided into 5 groups: Group A = Control, B = Aluminum chloride (200 mg/kg), C = 1000 mg/kg of NAC + Aluminum chloride (200 mg/kg), D = 1000 mg/kg of NAC, E = Aluminum chloride (200 mg/kg) was orally administered daily for 3 weeks and discontinued for one week. Frontal Cortex harvested for histological analysis using Haematoxylin and Eosin stain, Cresyl Fast Violet stain for Nissl granules and Glial fibrillary acidic protein immunohistochemistry specific for astrocytes. Aluminum significantly induced oxidative stress, coupled with marked neurons necrosis, chromatolysis and gliosis in the frontal cortex, upon NAC administration, there was neuro anti-inflammatory response as seen in the significant reduction in astrocytes expression, neuronal cell death and Nissl body aggregation which attenuates neuropathological deficits induced by Al 3+ . It was shown that aluminum is a neurotoxin mediating AD-like oxidative stress, NAC has a therapeutic potential associated with its potent in vivo interaction with astrocytes in response to Al 3+ neuro-inflammation seen in positive expression of Nissl granules and glial cells in addition to possibility of endogenous glutathione neuroprotection after withdrawal of stress mediator in neurodegeneration. Graphical abstract.

Ginsenoside Rg1 is the main active ingredient of Panax ginseng with the activity of neuroprotective, antioxidant and strengthening the immune system. Therefore, we hypothesized that Rg1 may afford anti-aging effects although the mechanism remains to be elucidated. In this study, chemically induced aging mice were established by consecutive administration of D-galactose and AlCl 3 . We found that Rg1 effectively ameliorates spatial learning and memory deficits in aging mice demonstrated by their improved performance in step down avoidance tests and Morris water maze experiments. Rg1 restored aging-induced decline of FGF2 and BDNF, reactivated TrkB/Akt signaling pathways in the hippocampus and prefrontal cortex to inhibit apoptosis, for the expression of anti-apoptotic protein Bcl-2 and apoptosis promoting enzyme cleaved-Caspase3 were antagonistically restored. Therefore, these results established the anti-aging effects of Rg1, and FGF2, BDNF and associated signaling pathways might be promising targets. Our data may provide a new avenue to the pharmacological research and diet therapeutic role of ethnic products such as Rg1 in anti-aging and aging associated diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aluminium is a ubiquitous element that occurs naturally in the soil making human exposure to it is unavoidable. Tyrosol is present in olive oil and is known to have antioxidant effects. Therefore, the present study explores the toxic effects of aluminium chloride (AlCl 3 ) and evaluates the possible protection by tyrosol in male rats. Testicular injury was induced by the administration of AlCl 3 (34 mg kg -1  day -1 ). Rats were treated with either tyrosol (20 mg kg -1 day -1 ) or AlCl3 (34 mg kg -1 day -1 ). The experiment lasted for 10 weeks. Biochemical, histopathological and protein expression profiles were determined to decipher the role of tyrosol in protecting the cellular damage. Further, histomorphometric analyses of testes showed deranged architecture along with other noted abnormalities. AlCl 3 group rats' testes showed decreased GSH levels, CAT activities, Nrf-2, HO-1, bcl-2 expressions and sperm motility whereas increased caspase-3 expressions, MDA levels, abnormal and dead/live sperm ratio. However, tyrosol treatment attenuated these changes. The present results demonstrate the beneficial role of tyrosol treatment in AlCl 3 induced testicular toxicity alterations of rat., (© 2019 Blackwell Verlag GmbH.)

Objective: The present study aims to investigate the neuroprotective effect of caffeine against aluminum chloride (AlCl 3 )-induced neurotoxicity in rats. Methods: Twenty-one male albino rats were divided into 3 groups: control, AlCl 3 -intoxicated group that received daily oral administration of AlCl 3 (100 mg/kg for 30 days) and protected group injected daily with caffeine (20 mg/kg intraperitoneally) one hour before oral administration of AlCl 3 for 30 days. Levels of lipid peroxidation, reduced glutathione, and nitric oxide and the activities of acetylcholinesterase (AchE) and Na + /K + -ATPase were measured spectrophotometrically. Tumor necrosis factor-α (TNF-α) was evaluated by ELISA kit. Results: The data revealed evidence of oxidative and nitrosative stress in the cerebral cortex, hippocampus, and striatum of AlCl 3 -intoxicated rats. This was indicated from the increased levels of lipid peroxidation and nitric oxide together with the decreased level of reduced glutathione. Moreover, the daily AlCl 3 administration increased AchE and Na + /K + -ATPase activities and the level of TNF-α in the selected brain regions. Protection with caffeine ameliorated the oxidative stress induced by AlCl 3 in the cerebral cortex, hippocampus, and striatum. In addition, caffeine restored the elevated level of TNF-α in the hippocampus and striatum. This was accompanied by an improvement in the activities of AchE and Na + /K + -ATPase in the studied brain regions. Discussion and conclusions: The present findings clearly indicate that caffeine provides a significant neuroprotection against AlCl 3 -induced neurotoxicity mediated by its antioxidant, anti-inflammatory, and anticholinesterase properties.

This study aimed to verify the chelating, antioxidant and cytoprotective activities of Psidium brownianum Mart. Ex DC against mercury and aluminum. The ethanolic extract, as well as the tannic and flavonoid fractions, were prepared and subjected to liquid chromatography-mass spectrometry analysis. Ferric ion reduction and antioxidant activity measurement using the FRAP method were performed with P. brownianum. After determining the sub-allelopathic doses, germination tests using Lactuca sativa (lettuce) seeds were performed. The main compounds identified in the extract and fractions were: quercetin and its derivatives; myricetin and its derivatives; gallic acid; ellagic acid; quinic acid and gallocatechin. The Minimum Inhibitory Concentration (MIC) for all samples were ≥ 1024 μg/mL. The flavonoid fraction in association with mercury chloride demonstrated cytoprotection (p < 0.001). The sub-allelopathic concentration used was 64 μg/mL. The extract and fractions were cytoprotective for radicles and caulicles when assayed in association with mercury and against aluminum for radicles. This suggests that the P. brownianum extract and its fractions present cytoprotective activity, possibly related to the antioxidant effect of secondary metabolites, especially flavonoids., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the antioxidant effect of aqueous Lawsonia inermis leaf extract on aluminum-induced oxidative stress and the histology of the pituitary gland of adult Wistar rats., Methods: Thirty-five adult male Wistar rats weighing between 100-196g and 15 mice of the same weight range were included in the study. Lawsonia inermis extracts and aluminum chloride (AlCl 3 ) were administered for a period of three weeks to five rats per group. The subjects in Group 1 (control) were given pellets and distilled water. Group 2 received 60mg/kg/d of aqueous extract of Lawsonia inermis. Group 3 was given 0.5mg/kg/d of AlCl 3 . Group 4 was administered 0.5mg/kg/d of AlCl 3 and 60mg/kg/d of aqueous Lawsonia inermis extract orally. Group 5 received 0.5mg/kg/d of AlCl 3 and 75mg/kg/d of aqueous Lawsonia inermis extract orally. Group 6 was given 0.5mg/kg/d of AlCl 3 and 100mg/kg/d of aqueous Lawsonia inermis extract orally. Group 7 was administered 0.5mg/k/d of AlCl 3 and 5mg/Kg/d ascorbic acid in distilled water orally. Twenty-four hours after the last administration, the animals were weighed, sedated with chloroform, and had their pituitary glands located, removed, and weighed on an electronic analytical balance., Results: Decreased cell counts were observed in the pituitary gland micrographs of the Wistar rats given 0.5mg of aluminum chloride, whereas the Wistar rats given 0.5mg of aluminum chloride and varying doses of Lawsonia inermis had increased dose-dependent cell counts., Conclusion: Aqeuous Lawsonia Inermis leaf extract increased the cell counts of the pituitary glands of adult male Wistar rats, in addition to alleviating aluminum-induced oxidative stress.

Aluminum (Al) had well-identified adverse influences on the nervous system mainly through the creation of reactive oxygen species (ROS). Melatonin works as an antioxidant through the inhibition of ROS and attenuating peroxidation of lipids. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a pivotal transcription factor which controls the transcription of antioxidant enzymes. This study was conducted to determine the potential neuroprophylactic impacts of melatonin in aluminum chloride (AlCl 3 )-initiated neurotoxicity including potential mechanism(s) of action and relevant signaling in rats. Thirty-six male rats were distributed into 4 groups: Control; AlCl 3 (50 mg/kg bwt, i.p, 3 times weekly for 3 months); melatonin (5 mg/kg bwt, i.p daily for 2 weeks before AlCl 3 and sustained for the next 3 months); and melatonin with AlCl 3 . Neuronal alterations were histopathologically and biochemically evaluated. The neuronal antioxidant-related genes and relevant Nrf2 protein expression were determined by real-time PCR and Western blotting, respectively. The current data showed a substantial increase in brain damage biomarkers, acetylecholinesterase (AchE) activity, and malondialdehyde (MDA) content while the enzymatic antioxidant expression as glutathione-s-transferase (GST), catalase (CAT), and superoxide dismutase (SOD) were substantially attenuated in the aluminum-treated group, with cleared histopathological changes as inflammatory cell infiltration with neuronal degeneration. Supplementation of melatonin resulted in an obvious amelioration in all previous abnormal alteration observed in AlCl 3 -treated rats rather than increased Al burden and/or altered Fe and Cu homeostasis with upregulating both total and phosphorylated Nrf2 expression. Therefore, the study concluded that melatonin has a potential ability to be neuroprophylactic against Al-induced neurotoxic effect and oxidative damage in the rat brain through upregulating and instigating Nrf2 signaling apart from metal chelation.

Eugenia dysenterica ex DC Mart. (Myrtaceae), popularly known as "cagaita," is a Brazilian plant rich in polyphenols and other antioxidant compounds. Aiming to evaluate the potential use of cagaita in pathologies involving oxidative stress, such as neurodegenerative disorders, this study investigated its antioxidant potential and neuroprotective effect. Electrochemical approaches and aluminium-induced neurotoxicity were used to determine respectively in vitro and in vivo antioxidant properties of cagaita. Voltammetric experiments were carried out in a three-electrode system, whose working electrode consisted of glassy carbon. Male Swiss mice were administered with AlCl 3 orally at a dose of 100 mg/kg/day and with cagaita leaf hydroalcoholic extract (CHE) at doses of 10, 100, and 300 mg/kg/day. The redox behavior of CHE presented similar features to that of quercetin, a widely known antioxidant standard. CHE prevented mouse memory impairment which resulted from aluminium intake. In addition, biochemical markers of oxidative stress (catalase, superoxide dismutase activity, and lipid peroxidation) were normalized by CHE treatment. The potential of CHE to prevent aluminium-induced neurotoxicity was reflected at the microscopic level, through the decrease of the number of eosinophilic necrosis phenotypes seen in treated groups. Moreover, the protective effect of CHE was similar to that of quercetin, which was taken as the standard. These findings showed that the CHE of cagaita leaves has a potential to protect the brain against oxidative-induced brain damage.