Gelatin/polyvinyl alcohol loaded magnesium hydroxide nanocomposite attenuates neurotoxicity and oxidative stress in Alzheimer's disease induced rats.

Amyloid-β (Aβ) plaque formation, neuronal cell death, mitochondrial and cholinergic dysfunction are key indicators of Alzheimer's disease (AD). In this study, gelatin and polyvinyl alcohol (PVA) were tethered with magnesium hydroxide (Mg(OH)2) to synthesize nanocomposite (Ge/PVA/Mg(OH)2) through alkali co-precipitation. The characterization studies using FT-IR, XRD, DLS, and SEM-EDX confirmed the successful formation of Ge/PVA/Mg(OH)2 nanocomposite. Further, in vitro study it clearly demonstrated the impact of Ge/PVA/Mg(OH)2 nanocomposite on biocompatibility, cellular uptake, reduced Aβ protein expression and protection of neuronal cell death. The confocal study further confirmed the down-regulation of Aβ expression. The subsequent in vivo analysis witnessed the protective effect of Ge/PVA/Mg(OH)2 nanocomposites on the cognitive and synaptic impairments of AD in intraceribroventricular streptozotocin (ICV-STZ) treated rats. Oxidative stress, antioxidant enzymes, cholinergic and mitochondrial complex activity were conducted and revealed that the Acetylcholineesterase (AChE) and Malondialdehyde (MDA) activities were significantly decreased by contrast the antioxidant enzyme activities were found to be increased in the cortex and hippocampus regions of the brain. Thus, the present investigation recommends Ge/PVA/Mg(OH)2 nanocomposite to target AD and clinical translation.

Rajkumar M ，Vimala K ，Tamiliniyan DD ，Thangaraj R ，Jaganathan R ，Kumaradhas P ，Kannan S ... -  《-》

Gelatin/polyethylene glycol-loaded magnesium hydroxide nanocomposite to attenuate acetylcholinesterase, neurotoxicity, and activation of GPR55 protein in rat models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease marked by mitochondrial dysfunction, amyloid-β (Aβ) aggregation, and neuronal cell loss. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for insulin receptors in diabetes therapy, but GPR55's role in AD is still unidentified. Gelatin (GE) and polyethylene glycol (PEG) polymeric hydrogels are commonly used in the drug delivery system. Therefore, the aim of the present study was the preparation of magnesium hydroxide nanocomposite using Clitoria ternatea (CT) flower extract, GE, and PEG (GE/PEG/Mg(OH)2NCs) by the green precipitation method. The synthesized GE/PEG/Mg(OH)2NCs were used to determine the effect of GPR55 activation of intracerebroventricular administration on streptozotocin (ICV-STC)-induced cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive deficits. The GE/PEG/Mg(OH)2NCs were administered following bilateral ICV-STC administration (3 mg/kg) in experimental rats. Neurobehavioral assessments were performed using a Morris water maze (MWM) and a passive avoidance test (PA). Cholinergic and antioxidant activity, oxidative stress, and mitochondrial complex activity were estimated in the cortex and hippocampus through biochemical analysis. Inflammatory markers (TNF-α, IL-6, and IL-1β) were determined using the ELISA method. Our study results demonstrated that the GE/PEG/Mg(OH)2NCs treatment significantly improved spatial and non-spatial memory functions in behavioral studies. Moreover, the treatment with GE/PEG/Mg(OH)2NCs group significantly attenuated cholinergic dysfunction, oxidative stress, and inflammatory markers, and also highly improved anti-oxidant activity (GSH, SOD, CAT, and GPx) in the cortex and hippocampus regions. The western blot results suggest the activation of the GPR55 protein expression through GE/PEG/Mg(OH)2NCs. The histopathological studies showed clear cytoplasm and healthy neurons, effectively promoting neuronal activity. Furthermore, the molecular docking results demonstrated the binding affinity and potential interactions of the compounds with the AChE enzyme. In conclusion, the GE/PEG/Mg(OH)2NCs treated groups showed reduced neurotoxicity and have the potential as a therapeutic agent to effectively target AD.

Rajkumar M ，Navaneethakrishnan S ，Muthukumar S ，Thangaraj R ，Sivanandam M ，Vimala K ，Kannan S ... -  《-》

Chitosan/PLA-loaded Magnesium oxide nanocomposite to attenuate oxidative stress, neuroinflammation and neurotoxicity in rat models of Alzheimer's disease.

Rajkumar M ，Govindaraj P ，Vimala K ，Thangaraj R ，Kannan S ... -  《-》

The effects of polyvinyl alcohol-coated selenium nanoparticles on memory impairment in rats.

Some mineral elements exert beneficial neuroprotection, especially in the form of nanoparticles. The aim of the present study was to evaluate the effects of selenium nanoparticles (SeNPs) and polyvinyl alcohol (PVA)-coated SeNPs (PVA-SeNPs) on Alzheimer's disease (AD) in a rat model of AD. Twenty-eight rats were randomly divided into four groups of seven rats: control, Alz, Alz + Se, and Alz + Se-PV groups. PVA-SeNPs and SeNPs were chemically synthesized and orally administrated (0.4 mg/kg) to the AD rats for one month. AD was induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ). The memory function was assessed by the novel object recognition (NOR) and passive avoidance learning (PAL) tests. The expression of hippocampal brain-derived neurotrophic factor (BDNF) and stress oxidative markers (MDA and TAC), and the number of amyloid-beta (Aβ) plaques were assessed using ELISA kits, biochemical methods, and Congo red staining, respectively. The results of the behavioral tests showed that the discrimination index in the NOR test increased in the Alz + PVA-SeNPs group compared to the Alz group. Memory performance in the PAL task improved in the PVA-SeNPs and SeNPs groups compared to the Alz group. The level of the BDNF in both of the Alz treatment groups (PVA-SeNPs and SeNPs) showed a significant increase compared to the Alz group. MDA levels and Aβ plaques decreased in both NPs-treated Alz groups, while TAC levels decreased in all Alz groups. PVA-SeNPs were more effective than SeNPs in the improvement of the cognition deficit. The results suggest that PVA-SeNPs improve the cognition and memory deficit induced by an ICV injection of STZ through a decrease in the number of Aβ plaques and malondialdehyde levels and an increase in the BDNF levels.

Hashemi-Firouzi N ，Afshar S ，Asl SS ，Samzadeh-Kermani A ，Gholamigeravand B ，Amiri K ，Majidi M ，Shahidi S ... -  《-》

Grape Seed Proanthocyanidin Extract Ameliorates Streptozotocin-induced Cognitive and Synaptic Plasticity Deficits by Inhibiting Oxidative Stress and Preserving AKT and ERK Activities.

Gao WL ，Li XH ，Dun XP ，Jing XK ，Yang K ，Li YK ... -  《-》