The Late-onset Alzheimer's disease (LOAD) is progressive cognitive deficits associated with different abnormalities as cholinergic dysfunction, amyloid accumulation, inflammation, and oxidative stress Show more
The Late-onset Alzheimer's disease (LOAD) is progressive cognitive deficits associated with different abnormalities as cholinergic dysfunction, amyloid accumulation, inflammation, and oxidative stress. Magnolol is a polyphenolic compound that abrogated the neurodegenerative disease. The application of nanoparticles in medicine showed high bioavailability and low side effects for development of novel effective therapies. This study evaluated the neuroprotective potential of magnolol nanoparticles against streptozotocin (STZ) injected in intracerebroventricularly (ICV) induced Alzheimer's disease (AD) in rats. In current study, six groups of male Wister rats (10 rats/ group) were injected with STZ (2 mg/kg) in ICV bilaterally for induction of pathological features similar to AD. Rats were then treated with either magnolol or nano-magnolol or donepezil (p.o). Behavioral analysis was evaluated as the Morris Water Maze (MWM), Y-Maze, Novel Object Recognition (NOR), Passive Avoidance (PA), Elevated plus Maze (EPM), and Open Field Test (OFT). In addition, biochemical markers including brain acetylcholinesterase (AChE), glutathione-S-transferase (GST), B-secretase1 (BACE1) activities and nuclear factor kappa-B (NF-κB) were analyzed in hippocampal tissue. Data obtained showed that nano-magnolol significantly showed a neuroprotective effect in LOAD rat model by restoring GST activity and effectively decreased the activities of AChE, BACE1 and level of NF-κB compared to both donepezil and magnolol. Molecular docking studies indicated strengthen the affinity of magnolol to the BACE-1 active site. Nano-magnolol is promising in developing a new agent targeting cholinergic function, amyloidogenesis, neuro-inflammation, and oxidative stress reflecting its potent neuroprotective efficacy in AD treatment. Show less
The goal of this study was to analyze the association between the FTO rs17817449 (G>T), G protein beta3 subunit (GNB3) C825T and Melanocortin 4 receptor (MC4R) A822G single nucleotide polymorphism (SN Show more
The goal of this study was to analyze the association between the FTO rs17817449 (G>T), G protein beta3 subunit (GNB3) C825T and Melanocortin 4 receptor (MC4R) A822G single nucleotide polymorphism (SNP) with obesity in Saudi subjects. The subjects were divided into 2 groups according to BMI: Obese (BMI> 29.9) and non- obese control (BMI<24.9). Genotyping of the target genes were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis (RFLP). We demonstrated the association of the FTO genotype TT with increased weight, BMI and leptin levels in both males and females. However, there was no association of genotype TT with fasting blood glucose, triglycerides and cholesterol levels. Regarding GNB3 rs5443 polymorphism, the likelihood of obesity was linked to the TT genotype which was also associated with increased leptin levels. On the other hand, the SNP of MC4R A822G did not exhibit any significant association with obesity among studied subjects and showed only the presence of homozygous AA genotype. The polymorphism of FTO gene rs17817449 and GNB3 gene rs5443 (C825T) may be a genetic determinant of obesity in Saudi population whereas impact of MC4R Asn274Ser change could not be detected. Show less