No abstract

While nanotechnology has gained immense popularity in the research industry due to its improved efficacy compared to traditional counterparts, toxicological considerations and their regulations need to be elucidated. A strategic approach towards toxicological assessment of nanomedicine within the standard set of framework will not only motivate more research on the technology but it will also stir up the conventional drug delivery system.

No abstract

Background: Alzheimer’s disease (AD) impairs memory and cognitive functions in the geriatric population and is characterized by intracellular deposition of neurofibrillary tangles, extracellular deposition of amyloid plaques, and neuronal degeneration. Literature suggests that latent viral infections in the brain act as prions and promote neurodegeneration. Memantine possesses both anti-viral and N-methyl-D-aspartate (NMDA) receptor antagonistic activity. Objectives: This research was designed to evaluate the efficacy of antiviral agents, especially valacyclovir, a prodrug of acyclovir in ameliorating the pathology of AD based on the presumption that anti-viral agents targeting the Herpes simplex virus (HSV) can have a protective effect on neurodegenerative diseases like Alzheimer’s disease. Methods: Thus, we evaluated acyclovir’s potential activity by in-silico computational docking studies against acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase 1 (BACE-1). These findings were further evaluated by in-vivo scopolamine-induced cognitive impairment in rats. Two doses of valacyclovir, a prodrug of acyclovir (100 mg/kg and 150 mg/kg orally) were tested. Results: Genetic Optimisation for Ligand Docking scores and fitness scores of acyclovir were comparable to donepezil. Valacyclovir improved neurobehavioral markers. It inhibited AChE and BuChE (p<0.001) enzymes. It also possessed disease-modifying efficacy as it decreased the levels of BACE-1 (p<0.001), amyloid beta 1-42 (p<0.001), amyloid beta 1-40 (p<0.001), phosphorylated-tau (p<0.001), neprilysin (p<0.01), and insulin-degrading enzyme. It ameliorated neuroinflammation through decreased levels of tumour necrosis factor α (p<0.001), nuclear factor-kappa B (p<0.001), interleukin 6 (p<0.001), interleukin 1 beta (p<0.001), and interferon-gamma (p<0.001). It also maintained synaptic plasticity and consolidated memory. Histopathology showed that valacyclovir could restore cellular density and also preserve the dentate gyrus. Conclusion: Valacyclovir showed comparable activity to donepezil and thus can be further researched for the treatment of Alzheimer’s disease.

Purpose: A multifaceted treatment approach can be effective for Alzheimer's disease (AD). However, currently, it involves only symptomatic treatment with cholinergic drugs. Beneficial effects of high vitamin D levels or its intake in the prevention and treatment of cognitive disorders have been reported. Thus, the present study examined the preventive effect of vitamin D supplementation on AD progression and evaluated its impact on the accumulation or degradation of Aβ plaques. Methods: A single intraperitoneal injection of scopolamine was used to induce AD in rats. Treatment of vitamin D was provided for 21 days after the injection. Various behavioral parameters like learning, spatial memory and exploratory behavior, biochemical alterations in the brain homogenate and histology of the hippocampus were investigated. Results: Our results indicated that scopolamine-induced rats depicted cognitive deficits with high Aβ levels and hyperphosphorylated tau proteins in the brain tissue, while vitamin D supplementation could significantly improve the cognitive status and lower these protein levels. These results were supported by the histopathological and immunohistochemical staining of the hippocampal brain region. Furthermore, mechanistic analysis depicted that vitamin D supplementation improved the Aβ protein clearance by increasing the neprilysin levels. It also reduced the accumulation of Aβ plaques by lowering neuroinflammation as well as oxidative stress. Conclusion: The present findings indicate that vitamin D supplementation can delay AD progression by an increase in Aβ plaques degradation or reducing inflammation and oxidative stress.