Arbutin attenuates monosodium L-glutamate induced neurotoxicity and cognitive dysfunction in rats

Rafael

Behavioural Pharmacology

et al. 2023

Here, we investigate the effects of obesity induced by monosodium glutamate (MSG) on cognitive impairment and whether this model induces any alteration in the affinity, density, and subtypes of muscarinic acetylcholine receptors (mAChRs) in rat hippocampus. Healthy rats were used as controls, and MSG-obese rats were selected via the Lee index > 0.300. The effects of MSG-induced obesity on hippocampal spatial learning and memory processes were evaluated by using the working memory versions of the Morris’ water maze task and the evaluation of mAChRs by binding assay and their subtypes by immunoprecipitation assays. [3H]Quinuclidinyl benzilate specific binding analysis showed that the equilibrium dissociation constant (KD) did not differ between control and MSG, indicating that affinity is not affected by obesity induced by MSG. The maximum number of binding sites (Bmax) obtained in MSG subjects was lower than that obtained from control rats, indicating a decrease in the expression of total mAChRs. Immunoprecipitation assays reveal a decrease in the expression of M1 subtype of MSG when compared with control rats (M2 to M5 subtypes did not differ between control and MSG). We also observed that MSG promotes a disruption of the spatial working memory which was accompanied by a decrease in the M1 mAChR subtype in rat hippocampus, thus suggesting deleterious long-term effects besides the obesity. In conclusion, these findings provide new insights into how obesity can influence spatial learning and memory that is hippocampal-dependent. The data suggest that the M1 mAChR subtype protein expression is a potential therapeutic target.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The M1-muscarinic acetylcholine receptor subtype may play a role in learning and memory performance in the hippocampus of neonatal monosodium glutamate-obese rats

Rafael

Behavioural Pharmacology

et al. 2023

J Biochem & Molecular Tox

“…[ 32 ] In a different study conducted by Nwakanma et al, [ 33 ] it was revealed that KBrO 3 can cause dysfunctions in the cerebral cortex at high doses. Kumar et al [ 34 ] stated that ARB may provide therapeutic advantages in neurodegenerative brain dysfunctions by suppressing excitotoxic mechanisms. Dadgar et al [ 35 ] demonstrated that ARB lowered behavioral disorders and oxidative stress in an animal model in which Parkinson's disease was developed.…”

Section: Discussionmentioning

confidence: 99%

The protective effect of arbutin against potassium bromate‐induced oxidative damage in the rat brain

Akkoyun

Uyar

Akkoyun

et al. 2022

This study aimed to investigate the protective effects of arbutin (ARB) against brain injury induced in rats with potassium bromate (KBrO3). The rats were divided into four groups as Group 1: Control (0.9% NaCl ml/kg/day p.), Group 2: KBrO3 (100 mg/kg (gavage), Group 3: ARB (50 mg/kg/day p.), and Group 4: KBrO3 + ARB (100 mg/kg (gavage) + 50 mg/kg/day p.). At the end of the fifth day of the study, the rats in all groups were killed, and their brain tissues were collected. In the collected brain tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were measured, and routine histopathological examinations were made. The MDA levels in the group that was exposed to KBrO3 were significantly higher than those in the control group (p ˂ 0.001). In comparison to the KBrO3 group, the MDA levels in the KBrO3 + ARB group were significantly lower (p ˂ 0.001). It was observed that SOD and CAT enzyme activity levels were significantly lower in the KBrO3 group compared to the control group (p ˂ 0.001), while these levels were significantly higher in the KBrO3 + ARB group than in the KBrO3 group (p ˂ 0.001). Additionally, the group that was subjected to KBrO3 toxicity, as well as ARB administration, had much lower levels of histopathologic signs than the group that was subjected to KBrO3 toxicity only. Consequently, it was found that KBrO3 exposure led to injury in the brain tissues of the rats, and using ARB was effective in preventing this injury.

“…In addition, arbutin can perform various functions and effectively decrease heat and other detoxifying qualities (Bhalla et al 2023). It has been reported to mitigate the neurotoxicity of monosodium L-glutamate by reducing cognitive dysfunction, in ammatory markers and biochemical disturbances in the brain (Kumar et al 2021). According to our ndings, the study mentioned above is well correlated with our present study.…”

Section: )mentioning

confidence: 99%

Network Analysis and Molecular Mapping for Alzheimer’s Disease to Reveal the Drug Targets of Arbutin

Uvarajan,

Ravikumar,

Durairaj

2023

Preprint

Alzheimer's disease (AD) is a neurodegenerative disease that causes the degradation of brain cells. AD is the most common causative factor of dementia that leads to cognitive decline and loss of independence. Cholinesterase inhibitors and N-methyl-D- aspartate (NMDA) antagonists are currently available drugs to treat AD related symptoms. Several studies have proved that arbutin is found to be beneficial in treating various diseases thereby modulating its brain targets which further helps to reduce AD’s side effects. The present research is mainly focused to study the molecular pathways and to determine the mechanism of action of arbutin to mitigate AD using a system pharmacology approach. Bioinformatics tools are explored to identify arbutin's therapeutic targets for AD, including Cytoscape for network analysis, ShinyGo for gene ontology enrichment, and AutoDock for docking molecules. In a Cytoscape network, the Maximal Clique Centrality (MCC) algorithm of the CytoHubba plugin was used to determine the top ten hub genes. Out of 411 targets for arbutin and 395 targets for AD, 37 targets were selected and shared through the data filtering process. The biological activities of these 37 genes include post-translational regulation of the phosphorus metabolic process, response to abiotic stimulus, regulation of cell population proliferation, regulation of programmed cell death and response to oxygen-containing compounds. The top 10 enriched pathways were selected for future study from 284, including AD, cancer pathways, MAPK signaling, Diabetic cardiomyopathy and proteoglycans in cancer. Our results proved that arbutin can reduce the possibility of developing AD by modulating the activity of primary pathways groups, including its pharmacological mechanism of action in AD, revealing its ten therapeutic targets.