Aluminum Chloride-induced Neurotoxicity Research Articles

Safeguarding Neuronal Integrity: Unveiling Possible Role of NFκB in the Neuroprotective Efficacy of Andrographolide Contrary to Aluminium Chloride-induced Neurotoxicity and Associated Spatial Memory Impairments in Rats.

The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus. Prolonged dosing of AlCl3 (7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue. The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl3, effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl3, thereby maintaining the typical histoarchitectural arrangement of these regions. These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl3 exposure.

Sercocephalous latifolius fruit attenuates aluminum chloride-induced oxidative stress and neurotoxicity in Drosophila melanogaster via Drn1 regulation of the IMD signaling pathway

IntroductionAlzheimer disease (AD) is a form of dementia that is a heterogeneous dysfunction of various pathophysiological features. Its morphological characteristics consist of tau aggregates and amyloid plaques. The need for novel therapy in the treatment of AD is required. Hence use of antioxidant, natural products are widely employed for the management and treatment of AD and other neurodegenerative diseases. However, there are still a lot of limitations. Sercocephalous latifolius fruit (SLF) is also known as the African peach and has numerous well-being-endorsing advantages. The Chinese name of SLF is Feizhou hong tao, while the Nigeria (Yoruba) name is Eso Gberesi. It can be grown all over the world. SLF has anti-neurodegenerative properties, however, there is a lack of evidence on their probable molecular mechanism for novel therapeutic properties. Investigations have been conducted on the SFL which shows its medicinal capability, but its ability to attenuate neurodegenerative diseases such as AD is yet to be fully elucidated, and the molecular signally pathways whichmay serve as a therapeutic target. MethodsThe modulatory effect of SLF on aluminum chloride-induced neurotoxicity and oxidative stress in Drosophila melanogaster via Defense repressor-1 (Drn1) regulation of immune deficiency (Imd) signaling pathway which may be a useful therapeutic target. D. melanogaster was divided into nine groups. Group 1 served as the basal control as they were fed with a normal basal diet, group 2 served as the negative control as they were fed with Basal Diet and 0.5 ml of aluminum/100 ml distilled water, group 3 served as the positive control as they were fed with basal diet 0.5 ml aluminum chloride/100 ml distilled water and Garlic acid, group 4 and 5 were fed with basal diet and 0.1 and 1 % SLF respectively, group 6 and 7 were fed with basal diet, aluminum chloride and 0.1 and 1.0 % respectively, group 8 and 9 were fed with basal diet, garlic acid, aluminum chloride and 0.1 and 1.0 % SLF respectively. All the groups were left for seven days. The experiment was conducted for 3 months, and the fruit flies were changed every 5 days. ResultsSuperoxide dismutase, catalase, malondialdehyde, and nitric oxide enzymatic enzymes were assayed. However, the relative expression of Defense repressor-1 was also determined both in vitro and on aluminum-induced neurodegenerative D. melanogaster tissue. A significant increase was observed in the catalase when 0.1 % and 1 % were compared, it could be inferred that the extract proved effective at low concentrations, since its highest antioxidant potential was observed at low concentrations. The results revealed decrease in the activity of malondialdehyde, superoxide dismutase, and nitric oxide biological enzymes in the test groups. There was upregulation of Defense repressor -1 in groups 3, 4, 5, and 6, when compared with the positive and negative control, respectively. DiscussionThe result provides evidence that SLF has the potential of upregulating defense repressor genes and modulating biological antioxidant enzymes, which could be further exploited to fully understand the underlying molecular mechanisms responsible for the attenuation of neurotoxicity, oxidative stress, and neurodegenerative diseases such as AD. The results suggest that SLF may be useful as a therapeutic target in AD and other neurodegenerative diseases

Sweet basil (Ocimum basilicum) leaf and seed extracts alleviate neuronal dysfunction in aluminum chloride-induced neurotoxicity in Drosophila melanogaster Meigen model

Ocimum basilicum is an important medicinal plant and culinary herb generally known as sweet basil (SB). These plants are effective radical scavengers, that have been employed in treatment of nervous system disorders, and thus, could be beneficial for the management of neurodegenerative diseases (NDs). Current clinical treatments for NDs present several side effects, therefore, there is need to develop new treatments that can mitigate these deadly diseases. Hence, this study investigated the neuroprotective activities of SB leaf and seed in aluminum chloride (AlCl3)-induced toxicity in Drosophila melanogaster. HPLC characterization of the leaves and seeds were carried out. AlCl3-diet was used to induce neurodegeneration and treated flies received SB leaf and seed extracts-supplemented diet. Survival and locomotor performance activities/levels of oxidative biomarkers [reactive oxygen species (ROS), thiobarbituric acid reactive species (TBARS), total thiol, catalase, superoxide dismutase (SOD) and glutathione-S-transferase (GST)], enzymes linked with neurodegeneration (acetylcholinesterase (AChE) and monoamine oxidase (MAO)) were investigated. SB leaf had significantly (p < 0.05) higher polyphenol contents; gallic acid and P-coumaric acid were the most abundant polyphenol in the leaf and seed respectively. Percentage survival and locomotor rates, level/activities of total thiol, catalase, SOD and GST were significantly (p < 0.05) reduced while ROS, TBARS, AChE and MAO activities were significantly (p < 0.05) increased in AlCl3-diet-fed flies. Treatment with SB leaf and seed diet lessened these observed impairments. However, SB leaf had better neuroprotective activities that could be related to the observed higher phenolic constituents. Hence, SB leaf diet may offer improved therapeutic effect in NDs.

Ameliorative role of diets fortified with Artocarpus altilis in a Drosophila melanogaster model of aluminum chloride-induced neurotoxicity

Backgrounds: Artocarpus altilis (breadfruit) belongs to the family Moraceae. Artocarpus altilis possesses antioxidative, anti-inflammatory, and anti-proliferative properties. Aluminum (Al) is extensively utilized for consumer products, cooking utensils, pharmaceuticals, and industries. Indication for the neurotoxicity of Al is investigated in various studies, notwithstanding the precise mechanisms of Al toxicity are yet to be fully elucidated, and, which requires novel therapy. In this study, we determined the ameliorative role of Artocarpus altilis on aluminum chloride-induced neurotoxicity in Drosophila melanogaster.MethodsVarying concentration of the extract were used to formulate diets for 6 groups of flies. Group 1 contained basal diet, group 2 contained basal diet and aluminium chloride (AlCl3), group 3 contained basal diet + 0.1% unseeded breadfruit (UBF), group 4 contained basal diet + 1% unseeded breadfruit, group 5 and 6 contained basal diet + AlCl3 + 0.1% and 1% unseeded breadfruit. Assays such as acetylcholinesterase activity, malondialdehyde (MDA) concentration level, catalase activity, and superoxide dismutase (SOD) activity were carried out after 7 days of exposure respectively.ResultsThe results showed low activity of acetylcholinesterase activity and MDA level and high catalase and SOD activity in the pretreated and post-treated flies with Artocarpus altilis compared to the normal and negative control respectively.ConclusionsTaken together, Artocarpus altilis is a promising prophylactic, antiacetylcholinesterase, and antioxidant plant in the prevention, management and treatment of neurodegenerative diseases.Graphical

The protective effects of sesamol and/or the probiotic, Lactobacillus rhamnosus, against aluminum chloride-induced neurotoxicity and hepatotoxicity in rats: Modulation of Wnt/β-catenin/GSK-3β, JAK-2/STAT-3, PPAR-γ, inflammatory, and apoptotic pathways.

Introduction: Aluminium (Al) is accumulated in the brain causing neurotoxicity and neurodegenerative disease like Alzheimer's disease (AD), multiple sclerosis, autism and epilepsy. Hence, attenuation of Al-induced neurotoxicity has become a "hot topic" in looking for an intervention that slow down the progression of neurodegenerative diseases. Objective: Our study aims to introduce a new strategy for hampering aluminum chloride (AlCl3)-induced neurotoxicity using a combination of sesamol with the probiotic bacteria; Lactobacillus rhamnosus (L. rhamnosus) and also to test their possible ameliorative effects on AlCl3-induced hepatotoxicity. Methods: Sprague-Dawley male rats were randomly divided into five groups (n = 10/group) which are control, AlCl3, AlCl3 + Sesamol, AlCl3 + L. rhamnosus and AlCl3 + Sesamol + L. rhamnosus. We surveilled the behavioral, biochemical, and histopathological alterations centrally in the brain and peripherally in liver. Results: This work revealed that the combined therapy of sesamol and L. rhamnosus produced marked reduction in brain amyloid-β, p-tau, GSK-3β, inflammatory and apoptotic biomarkers, along with marked elevation in brain free β-catenin and Wnt3a, compared to AlCl3-intoxicated rats. Also, the combined therapy exerted pronounced reduction in hepatic expressions of JAK-2/STAT-3, inflammatory (TNF-α, IL-6, NF-κB), fibrotic (MMP-2, TIMP-1, α-SMA) and apoptotic markers, (caspase-3), together with marked elevation in hepatic PPAR-γ expression, compared to AlCl3 -intoxicated rats. Behavioral and histopathological assessments substantiated the efficiency of this combined regimen in halting the effect of neurotoxicity. Discussion: Probiotics can be used as an add-on therapy with sesamol ameliorate AlCl3 -mediated neurotoxicity and hepatotoxicity.

Ameliorative Effect of Grape Seed Oil on Aluminium Chloride Induced Neurotoxicity on Rats

Aims: Neurodegenerative disorder is characterized by progressive loss of structure and function of neurons. Exposure to aluminum causes neurodegenerative disorders like dementia, and Alzheimer's disease (AD). The present study was designed to examine the ameliorative effect of grape seed oil extraction aluminium chloride induced neurotoxicity in Wistar rats.&#x0D; Methodology: Wistar rats were administered with aluminium chloride (175 mg/kg. p.o.) for 28 days to generate neurotoxicity model. Attenuation effect of grape seed oil against aluminium chloride toxicity by oral administration adjunctly from day 18. Behavioral and locomotor activity was determined using passive avoidance test, open field test, actophotometer and rota rod test. Biochemical parameter such as acetylcholinesterase (AChE) activity andsuperoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) activity were assessed in brain samplesand histology of brain tissue were assessed on the final day of the experiment.&#x0D; Results: Aluminium chloride treatment significantly decreases cognitive function and open field test with a significance decrease in the acetylcholinesterase and antioxidant (SOD, CAT, GR) activity level. Also, the histopathological examination shows significance decrease in the neuronal cell density in hippocampal region. Grape seed oil treated with aluminum chloride neurotoxic groups alleviates all the toxicity induced by the aluminum chloride. Histopathological studies in the hippocampus and cortex of the rat brain also supported that the grape seed oil markedly reduced the toxicity of aluminium chloride.&#x0D; Conclusion: Supplementation of grape seed oilexhibited with beneficial and neuroprotective role on aluminium chloride induced neurotoxicity in Wistar rat modelby improving the cognitive memory and antioxidant enzyme level.

Effects of baicalein with memantine on aluminium chloride-induced neurotoxicity in Wistar rats.

Alzheimer's disease is a progressive neurodegenerative condition. It is one of the most common 28 forms of dementia accounting for 60-80% of people suffering from dementia. There are very few medications that are approved for the treatment of Alzheimer's disease. Baicalein, belonging to the flavone subclass of flavonoids, has been reported to have a neuroprotective effect by reducing oxidative stress and neuroinflammation, inhibiting the AChE enzyme, and reducing amyloid protein aggregation and toxicity. Memantine is one of the most important drugs used for treating Alzheimer's disease. The purpose of this work was to study the effect of baicalein with memantine on aluminum chloride-induced neurotoxicity in Wistar rats. Aluminum chloride (100mg/kg p.o.) was administered for 42days in male Wistar rats to induce neurotoxicity. Baicalein alone (10mg/kg) and a combination of baicalein (5mg/kg and 10mg/kg) with memantine (20mg/kg) were administered for 42days. Treatment of baicalein with memantine showed significant improvement in behavioral parameters. The combination reduced oxidative stress and the formation of β-Amyloid plaques and increased brain-derived neurotrophic factor (BDNF) expression. Based on findings, it can be concluded that treatment with baicalein and memantine may slow the progression of neurodegeneration in rats.

Evaluation of anti-Alzheimer activity of Echinacea purpurea extracts in aluminum chloride-induced neurotoxicity in rat model

Alzheimer's disease (AD) is one of the neurodegenerative illnesses that impair individual life & increase the demand for caregivers with no available curative medication right now. Therefore, there is a growing concern about employing herbal medicine to limit AD progression & improve patients' life quality, thus potentiating its add-on therapy. In addition, herbs are cost-effective & accessible with nearly no side effects. In the same vein, our study aimed to investigate the potency of Echinacea purpurea (EP) flower extracts to ameliorate the neurodegenerative effect of Aluminum chloride (AlCl3) in a rat model. Moreover, mechanistic studies, including impact on the cholinesterase activity, redox status, inflammatory mediators, behavior performance, glucose level & histopathology, were carried on. Our results showed that 250 mg/kg of Aqueous (AQ) & Alcoholic (AL) extracts of EP inhibited cholinesterase, restored oxidative balance, down-regulated IL-6 & TNF-α cytokines & improved behavior performance in vivo that was reflected in the brain picture by decreasing neuronal degeneration & amyloid plaques in cerebral cortex & hippocampus. The potency of both extracts was compared to reference drugs & AlCl3 positive control group. The AQ extract showed greater potency against COX-1, COX-2 & α-amylase in vitro, while the AL extract was more potent against cholinesterase in vitro, inflammatory cytokines, behavior & pathological improvement in vivo. Conclusively EP overcame AlCl3-induced neurobehavioral toxicity in the rat model via different pathways, which support its regular administration to postpone progressive neural damage in AD patients.

Hibiscus sabdariffa calyx protect against oxidative stress and aluminium chloride-induced neurotoxicity in the brain of experimental rats.

We evaluated the antioxidant and neuroprotective potentials of extracts of Hibiscus sabdariffa calyx in Wistar albino male rats injected intraperitoneally with aluminium chloride at a dose of 7mg/kg/day. Phytochemical screening of H. sabdariffa calyx show that coumarin glycosides and steroid were absent after drying at 50oC. At 30oC, there were significant (p<0.05) highest amounts of phenols, flavonoids, alkaloids, tannin, and saponin. The extracts showed significantly (p<0.05) high dose-dependent antioxidant activities. MDA significantly (p<0.05) increased, while GSH, GPX, SOD, CAT activities significantly (p<0.05) decreased in the brain of the experimental rats induced with AlCl3, while treatment with the extracts reversed these effects to a relatively normal level. At doses of 500 and 1000mg/kg body weight, the extracts of the calyx dried at 30oC exhibited the highest capacity to increase the activities of GSH and GPx. Also, AlCl3 caused significant increases (p<0.05) in the percentage inhibition of acetylcholinesterase and butyrylcholinesterase activities, and a significantly (p<0.05) lower protein levels in the brain of the test rats, while treatment with the extracts, at low and high doses, significantly (p<0.05) reversed these effects in the rat brain to near normal.H. sabdariffa exhibited a good potential to protect against oxidative stress and neurotoxicity.

The neuroprotective effect of Xylopia parviflora against aluminum chloride-induced neurotoxicity in rats

Neurodegenerative disease such as Alzheimer’s disease, are progressive disorders which has been linked to oxidative imbalance and associated perturbations characterised by loss of memory, cognition and cholinergic deficit. To date, cholinesterase inhibition and neuroprotection are the two major strategies in drug development. Xylopia parviflora (Annonacea family) is a spice consumed in Cameroon and has been used in traditional medicine to treat various pains. In this study, X. parviflora was evaluated on behavioural studies, ion homeostasis, cholinesterase inhibitory and antioxidant activities. Rats were exposed to aluminium chloride (75 mg/kg) during 60 days, and were treated with the extract of X. parviflora (150 and 300 mg/kg BW) and two drugs references (Donepezil and Curcumin). Behavioural parameters were assessed using the Morris-Maze test and the Open Field, followed by biochemical investigations, namely, cholinesterase enzyme activity (AChE and BChE), oxidative stress (NO, MDA, GSH level, SOD and Catalase activities) and ion homeostasis (Mg2+ and Ca2+ levels). AlCl3 administration shows a decrease in learning and memory improvement during behavioural studies, significant alteration of the central cholinergic system characterised by an increase in AChE and BChE activities to 2.72 ± 0.002 mol/min/g and 5.74 ± 0.12 mol/min/g respectively, disturbance of ion homeostasis with an increase in Ca2+ level (25.68 ± 3.78 μmol/mg protein) and a decrease in Mg2+ level (15.97 ± 2.05 μmol/mg protein) and an increase in oxidative stress compared to the positive control group. Treatment with the different doses of X. parviflora increased memory and improved locomotion, improved cholinesterase activities, ion homeostasis and stabilized brain oxidative stress levels. The study suggests that X. parviflora could potentially be used for the management of some biochemical alterations associated with Alzheimer’s disease. It could even be a good alternative to chemical drugs for neurotoxicity and memory enhancement.

Silibinin-loaded nanostructured lipid carriers (NLCs) ameliorated cognitive deficits and oxidative damages in aluminum chloride-induced neurotoxicity in male mice

Aluminum chloride (AlCl3) and its accumulation in the brain are associated with neurodegenerative disease. Recent investigations have illustrated that silibinin is known to have neuroprotective properties. The present study investigates the neuroprotective effects of silibinin-loaded nanostructured lipid carriers (Sili-NLCs) against AlCl3-induced neurotoxicity in male mice. Sili-NLCs were prepared using the emulsification-solvent evaporation method and subjected to particle size, zeta potential, and entrapment efficiency (% EE) analysis. Mice were treated with AlCl3 (100 mg/kg/day, p.o.) and with the same concentration of silibinin and Sili-NLCs (50,100, and 200 mg/kg/day, p.o.) for 30 days in different groups. After treating animals, behavioral studies were assessed. Also, the brain tissue samples were collected from all mice to evaluate oxidative damage and histological changes. The particle size, polydispersity index, zeta potential, and entrapment efficiency (% EE) of prepared Sili-NLCs found 239.7 ± 4.04 nm, 0.082 ± 0.003, − 16.33 ± 0.15 mV, and 72.65 ± 2.03 %, respectively. Brain uptake studies showed that Sili-NLCs had a 5.7-fold greater uptake in the mice brain than the free drug. The AlCl3 caused significant cognitive impairment and increased the level of lipid peroxidation accompanied by decreasing antioxidant enzyme activity in the brain tissue. These findings correlated well with the histopathological experiments. Furthermore, treatment with Sili-NLCs significantly improved the AlCl3-induced cognitive impairment, neurochemical anomalies, and histopathological changes. Given these results, silibinin, when delivered using NLCs, is potentially more effective than free silibinin in decreasing AlCl3- induced neurotoxicity.

Celastrol and thymoquinone alleviate aluminum chloride-induced neurotoxicity: Behavioral psychomotor performance, neurotransmitter level, oxidative-inflammatory markers, and BDNF expression in rat brain

Exposure to aluminum chloride (AlCl3) induces progressive multiregional neurodegeneration in animal models by promoting oxidative stress and neuroinflammation. The current study was designed to assess the potential efficacy of the natural antioxidants celastrol and thymoquinone (TQ) for alleviating AlCl3-induced psychomotor abnormalities and oxidative-inflammatory burden in male albino rats. Four treatment groups were compared: (i) a vehicle control group, (ii) a AlCL3 group receiving daily intraperitoneal (i.p.) injection of AlCl3 (10 mg/kg) for 6 weeks, (iii) a AlCl3 plus TQ (10 mg/kg, i.p.) cotreatment group, and (iv) a AlCl3 plus celastrol (1 mg/kg, i.p.) cotreatment group. Open-field, rotarod, and forced swimming tests were conducted to assess locomotor activity, motor coordination, anxiety-like behavior, and depressive-like behavior. Acetylcholine (ACh), dopamine, and serotonin levels were measured in brain homogenates. Malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity were measured as oxidative stress markers, while tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) expression levels were measured as inflammatory markers. Brain derived neurotrophic factor (BDNF) mRNA was measured as an index for the endogenous neuroprotective response. Daily AlCl3 injection reduced free ambulation, impaired motor coordination, promoted anxiety- and depression-like behaviors, reduced whole-brain ACh, dopamine, and serotonin concentrations, increased MDA accumulation, reduced TAC, elevated TNF-α and IL-6, and suppressed BDNF mRNA expression. All of these effects were significantly reversed by TQ or celastrol cotreatment. Thus, TQ and celastrol may be promising treatments for AlCl3-induced neurotoxicity as well as neurodegenerative diseases involving oxidative stress and neuroinflammation.

Immunomodulatory and Antioxidant Effects of Eugenol on Aluminium Chloride-Induced Neurotoxicity in Wistar Rats

Aluminium and its compounds when taken orally can have negative impacts on a variety of enzymes leading to neurotoxicity. Apurinic endonuclease 1 (APE-1), a protein that performs multiple functions, including deoxyribonucleic acid (DNA) repair, is essential for cell survival. Thus, the determination of APE-1 with aluminium chloride (AlCl3) induced neuro-inflammation in Wistar rats was performed in this study. Wistar rats were divided into four groups, each with six animals. Group 1 received 100 mg/kg AlCl3 orally, Group 2 received 150 mg/kg eugenol, Group 3 received both 100 mg/kg AlCl3 and 150 mg/kg eugenol, and Group 4 received 0.8 ml/kg distilled water. Rats were euthanized after eight weeks, and brain tissues were homogenized and analysed. Oral administration of AlCl3 resulted in significant (p&lt;0.01) decreased APE-1, superoxide dismutase (SOD) and amyloid beta-40 (Aβ-40), and significant (p&lt;0.01) increased tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), inducible nitric oxide synthase (iNOS), myeloperoxidase, and nitric oxide (NO). Co-administration of AlCl3 and eugenol significantly increased (p&lt;0.01) APE-1, Aβ-40 and SOD, while significantly decreasing (p&lt;0.01) TNF-α, IL-1, iNOS and MPO levels. Our findings suggest that eugenol, by targeting these most potent hallmarks of neurodegeneration could be an effective alternative in its treatment.

Neuroprotective effect of Bryophyllum pinnatum flavonoids against aluminum chloride-induced neurotoxicity in rats

Toxic metals such as aluminum accumulation in the brain have been associated with the pathophysiology of several neurodegenerative disorders. Bryophyllum pinnatum leaves contain a vast array of polyphenols, particularly flavonoids, that may play a role in the prevention of toxic and degenerative effects in the brain. This study assessed the neuro-restorative potential of leaves of B. pinnatum enriched flavonoid fraction (BPFRF) in aluminum-induced neurotoxicity in rats. Neurotoxicity was induced in male Wistar rats by oral administration of 150 mg/kg body weight of aluminum chloride (AlCl3) for 21 days. Rats were grouped into five (n = 6); Control (untreated), Rivastigmine group, AlCl3 group and BPFRF group (50 and 100 mg/kg b.wt.) for 21 days. Neuronal changes in the hippocampus and cortex were biochemically and histologically evaluated. Expression patterns of acetylcholinesterase (AChE) mRNA were assessed using semi-quantitative reverse-transcription-polymerase chain reaction protocols. Molecular interactions of BPFRF compounds were investigated in silico. The results revealed that oral administration of BPFRF ameliorated oxidative imbalance by augmenting antioxidant systems and decreasing lipid peroxidation caused by AlCl3. BPFRF administration also contributed to the down-regulation of AChE mRNA transcripts and improved histological features in the hippocampus and cortex. Molecular docking studies revealed strong molecular interactions between BPFRF compounds, catalase, superoxide dismutase and glutathione peroxidase Overall, these findings suggest the neuroprotective effect of Bryophyllum pinnatum against aluminum-induced neurotoxicity.

Combination of donepezil and gallic acid improves antioxidant status and cholinesterases activity in aluminum chloride-induced neurotoxicity in Wistar rats.

The present study compared the effect of donepezil only and combination of donepezil and gallic acid on oxidative status and cholinesterase activity in the brain of Wistar rats administered AlCl3 for 60days. Twenty-eight rats (180 - 200g) were arbitrarily distributed into four groups of seven animals apiece. Group 1 served as normal control and received distilled water throughout the study. Group 2 animals received only AlCl3 throughout the study while animals in groups 3 and 4 were administered donepezil only (10mg/kg) and combination of donepezil (10mg/kg) and gallic acid (50mg/kg), respectively, in addition to AlCl3. Treatments were administered orally by gavage. At the end of the study, animals were sacrificed and activities of acetylcholinesterase, butyrylcholinesterase, superoxide dismutase (SOD) and catalase as well as levels of malondialdehyde (MDA), total thiol and nitric oxide (NO) were evaluated in the brain. Histopathological study was conducted on the hippocampus of experimental animals. Results showed that AlCl3 significantly (p < 0.05) increased brain activities of cholinesterases and levels of MDA and NO with a concomitant decrease in total thiol level as well as activities of SOD and catalase. Donepezil only and combination of donepezil and gallic acid reversed these alterations. Also, combination of donepezil and gallic acid significantly (p < 0.05) improved antioxidant status better than donepezil only. It could be concluded that a synergy might exist between gallic acid and donepezil especially in ameliorating oxidative stress associated with AlCl3-induced neurotoxicity.

The protective effect of Indian Catechu methanolic extract against aluminum chloride-induced neurotoxicity, A rodent model of Alzheimer's disease

Alzheimer's disease (AD) is the commonest neurodegenerative disorder with a wide array of manifestations, courses, and contributing causes. Despite being clinically characterized a long time ago; no treatment has been developed that could improve the pathology or slow down the disease manifestation- so far. Indian Catechu methanolic extract (ICME) has proved to have multiple beneficial effects that support its use in several disorders- especially those with complex etiology. In the present study, we evaluated the neuroprotective effect of ICME in a rat model of AD using Aluminum Chloride (AlCl3). The results showed that ICME could have a positive impact on the course of AD through its anticholinesterase effect and significant antioxidant effect which was reflected on the animals both on behavioral tests as well as hallmark pathological findings.

Beneficial effect of Hordeum vulgare extract against aluminum chloride induced neurotoxicity in Wistar rats

Aluminum is present in medicines and food. Its toxicity induces deleterious effects in various living organisms. At the same time, Hordeum vulgare a cereal known as an important nutritional source and also endowed with bioactive molecules. The objective of this study was to evaluate, on the one hand, the modifications induced by aluminum chloride in Wistar rats at the cerebral level and, on the other hand, to test the efficacy of the barley extract, Hordeum vulgare, (HEV) to restore the harmful effects of this studied metal with a concentration of 13 ml HEV/kg/day for a period of 21 days. The extraction of HEV by maceration resulted in an aqueous extract with a yield of 10.70%. Exposure to AlCl3 at a concentration of 100mg/kg, permitted to observe that the concentration of aluminium at the brain level is significantly high (p&lt;0.05) in the intoxicated rats compared to the control rats. On the other hand, the activity of alkaline phosphatase (PAL), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) indicated a decrease in the intoxicated rats. Indeed, the histological study showed very pronounced lesions in the brains of the poisoned rats resulting in necrosis and cellular spongiosis. In addition, the administration of HEV restored the activity of the various antioxidant enzymes with an improvement in brain tissue architecture in intoxicated rats treated with HEV which justifies the therapeutic virtues of H. vulgare in protecting against aluminium chloride-induced neurotoxicity.

Histological and Anti-oxidative Effects of Eugenol on Aluminium Chloride-Induced Neurotoxicity in Wistar Rats

Accumulation of aluminium chloride results in damage to different brain regions, and has been used to model damage to the hippocampus which can be associated with various neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The aim of this study was to assess the protective effects of eugenol on aluminium induced neurotoxicity in the hippocampus of adult Wistar rats. 30 adult Wistar rats were procured and divided into six groups with five animals in each group, namely: EGH (300 mg/kg eugenol), EGL (150 mg/kg eugenol), EGH+AL (300 mg/kg eugenol and 100 mg/kg AlCl3), EGL+AL (150 mg/kg eugenol and 100 mg/kg AlCl3), AL (100 mg/kg AlCl3) and CTRL (2 mL/kg distilled water). All Groups were treated orally for 21 days after which they were humanely sacrificed under 0.8 mL/kg ketamine as an anaesthetizing agent. Thereafter, brain tissues were removed and processed for histological demonstration, while the frontal lobe was homogenized and the resultant homogenate obtained was used to assay the levels of superoxide dismutase (SOD) activity. Rat body weights were measured before and after treatment. Aluminium resulted in a significant (p&lt;0.05) reduction in SOD activities. There was alteration in the histology of hippocampal neurons (CA1) and a significant (p&lt;0.01) reduction in body weight of animals. However, the administration of Eugenol was able to restore the activity of SOD. The use of Eugenol offers a promising prospect in the management of neurodegenerative diseases associated with aluminium toxicity.

Ameliorative role of diets fortified with Curcumin in a Drosophila melanogaster model of aluminum chloride-induced neurotoxicity

Aluminum is an environmental and industrial neurotoxicant known to induce oxidative damage and inflammation in tissues. Curcumin is a polyphenol with antioxidant and anti-inflammatory properties. Here, we evaluated Curcumin’s protective role in Aluminum Chloride (AlCl3)-induced toxicity in D. melanogaster. A 21-day survival analysis was carried out and subsequently, flies were exposed to AlCl3 (100 and 200 mg/kg diet) and/or Curcumin (0.2 and 0.5 mg/kg diet) for 7 days. Curcumin restored AlCl3-induced inhibition of glutathione S-transferase (GST) and catalase activities, as well as depletion of total thiol and glutathione contents. In addition, Curcumin ameliorated AlCl3-induced increase in acetylcholinesterase activity and accumulation of hydrogen peroxide and nitrite levels in flies. Additionally, AlCl3-induced disruption of climbing activity and emergence rate were ameliorated by curcumin in D. melanogaster (p < 0.05). Overall, Curcumin ameliorated AlCl3-induced toxicity in D. melanogaster. Therefore, it can be regarded as a therapeutic agent against AlCl3-induced toxicity.

Antioxidant and Neuroprotective Activities of the Mesocarp of &amp;lt;i&amp;gt;Raphia hookeri&amp;lt;/i&amp;gt; Fruit against Aluminum Chloride-Induced Neurotoxicity in Rats

This work aims to evaluate the antioxidant and protective effect of Raphia hookeri (Rh) fruit extracts and powders against aluminum induced neurotoxicity in rats. Extracts and powder were prepared using fruit mesocarp. Phytochemical contents (phenolic content and flavonoïd) and antioxidant in vitro activity were evaluated through the DPPH radical scavenging capacity, the ability to reduce ferric ion and Hydroxyl radical scavenging ability. The neurocognitive dysfunction, the activity of acetylcholinesterase (AChE) and activities of antioxidant in vivo indices were evaluated in the plasma, liver and brain of aluminum chloride (AlCl3) induced neurotoxicity in rats. The highest total phenolic (76.34 mg Eq AG/g of extract), flavonoïds’ contents (13.32 mg Eq CAT/g of extract), the best DPPH scavenging activity and the ability to reduce ferric ion (Fe3+) were obtained with aqueous extract. The administration of aqueous extract (200 and 400 g/kg bw) and powder (5% and 10 %) during 28 days resulted in a significant decrease (P Treatment with aqueous extract and powder of Rh mesocarp ameliorated neurobehavioral changes by enhancing antioxidant activities, cognitive functions. Therefore Rh would protect oxidative damage and preserve neurone functions.