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Neuroprotective effects of chitosan nanoparticles loaded with niruriflavone in an aluminium chloride-induced Alzheimer’s disease rat model

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Abstract

Objectives

Aluminium (Al) is also a popular neurotoxin that accelerates oxidative damage to biomolecules, which is correlated to the aetiology of Alzheimer's disease (AD). It is a common metal on the globe and can easily enter the body through food and water additives, cutlery, deodorants, and medications. It accumulates mostly in the brain's frontal cortex and hippocampus, and its elimination half-life in the human brain is estimated to be 7 years. It is known to be particularly vulnerable to AD, which is a crippling neurological ailment that primarily affects ageing adults and has a large socioeconomic impact. Niruriflavone (NF) is a natural flavonoid isolated from Phyllanthus niruri Linn. It demonstrated remarkable neuroprotective efficacy by inhibiting oxidative stress, acetylcholinesterase (AChE), and 5-lipoxygenase. The efficacy of NF was improved by the formulation of NF-loaded chitosan nanoparticle (NFLC). Consequently, the current study sought to assess the neuroprotective role of synthesized NFLC against aluminium chloride (AlCl3)-induced AD through the neurobehavioural, biochemical, and histopathological analysis.

Methods

Chronic administration of 100 mg/kg body weight of AlCl3 orally to Wistar rats resulted in AD. Neurobehavioural tests such the open-field test, elevated plus maze tests, and Morris water maze were used to evaluate the impact of NFLC treatment. The activity of the acetylcholinesterase enzyme and level of aluminium were also measured in AlCl3-induced AD rats. Cresyl violet staining was used to study the histopathological variations.

Results

NFLC treatment considerably increased learning and memory skills, improved the exploratory activities, and reduced the anxiety-related behaviour. NFLC-treated rats had lower Al levels and higher AChE inhibition activity. NFLC prevented the neuronal loss in the AD rat brains which was observed in histopathological studies.

Conclusion

NFLC helps to treat AD brought on by Al poisoning through the inhibition of AChE activity, oxidative stress, neuroinflammation, and neuronal loss. The development of these efficacious multitargeted NFLC could help people afflicted by AD.

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Availability of data and material

All data generated or analysed during this study are included in this article.

Abbreviations

Al:

Aluminium

AD :

Alzheimer’s disease

NF :

Niruriflavone

NFLC :

Niruriflavone-loaded chitosan nanoparticles

AChE:

Acetylcholinesterase

BBB :

Blood–brain barrier

AChEIs:

Acetylcholinesterase inhibitors

NMDA:

N-methyl-d-aspartate

CS :

Chitosan

EE :

Entrapment efficiency

AlCl3 :

Aluminium chloride

DTNB:

5,5’-Dithiobis-(2-nitrobenzoic acid)

MWM:

Morris water maze

OFT:

Open-field test

EPM:

Elevated plus maze

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Acknowledgements

The authors are thankful to the VIT, Tamilnadu, India, for providing all facilities required during the study. The authors declare that there are no funding interests that are directly or indirectly related to the work submitted for publication.

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Authors and Affiliations

  1. Department of Chemistry, School of Advanced Sciences, VIT, Vellore, Tamilnadu, 632014, India

    Gayathri Rajamanickam & Sreedharannair Leelabaiamma Manju

  2. Calcium Signalling Laboratory, Department of Research, National Neuroscience Institute, Singapore, 308433, Singapore

    Gayathri Rajamanickam

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Contributions

All authors contributed to the study conception. Original draft, methodology, data collection, and analysis were performed by GR. SLM has done the supervision of the study, review, and approval of the final drafts. All authors read the final drafts.

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Correspondence to Sreedharannair Leelabaiamma Manju.

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Conflict of interest

Rajamanickam Gayathri and S. L. Manju declares there is no conflict of interest.

Ethical approval

In compliance with the generally acknowledged guidelines for the use of experimental animals, the healthy adult Wistar rats of laboratory bred with permission from the Institutional Ethical Committee (KMCRET/IAEC/2020/35), KMCH, Tamil Nadu, India.

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This study does not include any studies with human.

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Rajamanickam, G., Manju, S.L. Neuroprotective effects of chitosan nanoparticles loaded with niruriflavone in an aluminium chloride-induced Alzheimer’s disease rat model. Toxicol. Environ. Health Sci. (2024). https://doi.org/10.1007/s13530-024-00207-x

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