Investigation of the Neuroprotective Potential of Meloxicam in Streptozotocin Induced Alzheimer's Disease

Abstract

Objective: Studies have shown the effects of NSAIDs on neuroprotection, particularly their ability to inhibit both COX isoforms but remain limited. Nonetheless, this dual inhibition presents a promising strategy for modulating inflammation in the brain. Thus, the aim of this study was to assess the neuroprotective properties of Meloxicam in a rat model of Alzheimer's disease induced by STZ. Methodology: Female SD rats were injected with STZ (i.c.v.) for the induction of AD in 6 different groups (n=6). The treatment commenced on the third day and involved the administration of Donepezil (5 mg/kg) along with Meloxicam at three different doses (1 mg/kg, 5 mg/kg, and 7 mg/kg) given daily over a period of 21 days. On the final day of treatment, cognitive function and behaviour were evaluated using modified Y-maze and Morri’s water maze tests. Subsequently, blood samples were collected and the animals were then euthanized. Brain tissue homogenate was utilized to perform oxidative parameters and histological examination was done with H&E stain. Results: Our results reveal that the STZ-induced Alzheimer's disease treatment groups receiving donepezil and meloxicam at doses of 5 mg/kg and 7 mg/kg exhibited notable enhancements in exploratory behavior and reduced escape latency times compared to the disease control groups. Furthermore, TNF-α levels significantly decreased in the meloxicam-treated groups at 5 mg/kg and 7 mg/kg, as well as in the standard treatment group. Furthermore, IL-6 levels decreased in the meloxicam-treated groups at 5 mg/kg and in the donepezil-treated group. Moreover, significant improvement was observed in the brain acetylcholine esterase activity of the donepezil and meloxicam-treated groups at 5 mg/kg. Also, there was significant improvement observed in serum SGPT level of the donepezil and meloxicam-treated groups at 5 mg/kg. Additionally, treatment groups significantly improved in the tryptophan hydroxylase and kynurenine levels compared to disease control, while kynurenic acid levels decreased in the treatment groups receiving donepezil and meloxicam. Furthermore, quinolinic acid level were reduced in the treatment groups receiving meloxicam at 5 mg/kg and donepezil group. Notably, meloxicam at 7 mg/kg exhibited improvements in oxidative parameters such as lipid peroxidation and reduced glutathione levels. Also, mortality was seen in the meloxicam-treated group at its higher dose level. Conclusion: Our results demonstrate that meloxicam significantly improves cognitive functions and reduces the levels of inflammatory biomarkers. Moreover, meloxicam treatment led to improvements in tryptophan and its metabolites compared to the disease control group. Additionally, meloxicam exhibited improvements in oxidative parameters. These results indicate that meloxicam holds promising potential as a therapeutic intervention for Alzheimer's disease.