Asiatic acid attenuates aluminium chloride-induced behavioral changes, neuronal loss and astrocyte activation in rats.

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 (AlCl3; 100 mg/kg b. wt.) dissolved in distilled water for 8 weeks or AA (75 mg/kg b. wt.) in combination with AlCl3. The results showed that AlCl3-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, AlCl3-intoxication enhanced neuronal loss and reactive astrogliosis in both regions. However, co-administration of AA with AlCl3 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.

Attenuative Effects of Fluoxetine and Triticum aestivum against Aluminum-Induced Alzheimer's Disease in Rats: The Possible Consequences on Hepatotoxicity and Nephrotoxicity.

BACKGROUND: Alzheimer's disease (AD) is a chronic neurological illness that causes considerable cognitive impairment. Hepatic and renal dysfunction may worsen AD by disrupting ß-amyloid homeostasis at the periphery and by causing metabolic dysfunction. Wheatgrass (Triticum aestivum) has been shown to have antioxidant and anti-inflammatory properties. This work aims to study the effect of aluminum on neuronal cells, its consequences on the liver and kidneys, and the possible role of fluoxetine and wheatgrass juice in attenuating these pathological conditions. METHOD: Rats were divided into five groups. Control, AD (AlCl3), Fluoxetine (Fluoxetine and AlCl3), Wheatgrass (Wheatgrass and AlCl3), and combination group (fluoxetine, wheatgrass, and AlCl3). All groups were assigned daily to different treatments for five weeks. CONCLUSIONS: AlCl3 elevated liver and kidney enzymes, over-production of oxidative stress, and inflammatory markers. Besides, accumulation of tau protein and Aß, the elevation of ACHE and GSK-3ß, down-regulation of BDNF, and ß-catenin expression in the brain. Histopathological examinations of the liver, kidney, and brain confirmed this toxicity, while treating AD groups with fluoxetine, wheatgrass, or a combination alleviates toxic insults. CONCLUSION: Fluoxetine and wheatgrass combination demonstrated a more significant neuroprotective impact in treating AD than fluoxetine alone and has protective effects on liver and kidney tissues.

JM-20 treatment prevents neuronal damage and memory impairment induced by aluminum chloride in rats.

The number of people with dementia worldwide is estimated at 50 million by 2018 and continues to rise mainly due to increasing aging and population growth. Clinical impact of current interventions remains modest and all efforts aimed at the identification of new therapeutic approaches are therefore critical. Previously, we showed that JM-20, a dihydropyridine-benzodiazepine hybrid molecule, protected memory processes against scopolamine-induced cholinergic dysfunction. In order to gain further insight into the therapeutic potential of JM-20 on cognitive decline and Alzheimer's disease (AD) pathology, here we evaluated its neuroprotective effects after chronic aluminum chloride (AlCl3) administration to rats and assessed possible alterations in several types of episodic memory and associated pathological mechanisms. Oral administration of aluminum to rodents recapitulates several neuropathological alterations and cognitive impairment, being considered a convenient tool for testing the efficacy of new therapies for dementia. We used behavioral tasks to test spatial, emotional- associative and novel object recognition memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study revealed that JM-20 prevented memory decline alongside the inhibition of AlCl3 -induced oxidative stress, increased AChE activity, TNF-α and pro-apoptotic proteins (like Bax, caspase-3, and 8) levels. JM-20 also protected against neuronal damage in the hippocampus and prefrontal cortex. Our findings expanded our understanding of the ability of JM-20 to preserve memory in rats under neurotoxic conditions and confirm its potential capacity to counteract cognitive impairment and etiological factors of AD by breaking the progression of key steps associated with neurodegeneration.

Melatonin Attenuates AlCl3-Induced Apoptosis and Osteoblastic Differentiation Suppression by Inhibiting Oxidative Stress in MC3T3-E1 Cells.

Aluminum (Al) inhibits osteoblast-mediated bone formation by oxidative stress, resulting in Al-induced bone disease. Melatonin (MT) has received extensive attention due to its antioxidant and maintenance of bone health effect. To evaluate the protective effect and mechanism of MT on AlCl3-induced osteoblast dysfunction, MC3T3-E1 cells were treated with MT (100 µM) and/or AlCl3 (8 µM). First, MT alleviated AlCl3-induced osteoblast dysfunction, presenting as the reduced apoptosis rate as well as increased cell viability, alkaline phosphatase (ALP) activity, and type I collagen (COL-1) level. Then, MT significantly attenuated AlCl3-induced oxidative stress, presenting as the reduced reactive oxygen species and 8-hydroxy-2'-deoxyguanosine levels as well as increased glutathione level and superoxide dismutase activity. Finally, MT protected MC3T3-E1 cells against p53-dependent apoptosis and differentiation suppression, as assessed by Caspase-3 activity, protein levels of p53, Bcl-2-associated X protein (Bax), B cell lymphoma gene 2 (Bcl-2), cytosolic Cytochrome c, Runt-related transcription factor 2 (Runx2), and Osterix, as well as the mRNA levels of Bax, Bcl-2, Runx2, Osterix, ALP, and COL-1. Overall, our findings demonstrate MT attenuates AlCl3-induced apoptosis and osteoblastic differentiation suppression by inhibiting oxidative stress in MC3T3-E1 cells.