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Centella asiatica Alleviates AlCl3-induced Cognitive Impairment, Oxidative Stress, and Neurodegeneration by Modulating Cholinergic Activity and Oxidative Burden in Rat Brain

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Abstract

Aluminum (Al) is linked to the development of many neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease, and autism. Centella asiatica (CA) is a regenerating herb traditionally used to stimulate memory. This study was designed to assess the neuroprotective role of ethanolic extract of CA (CAE) in AlCl3-induced neurological conditions in rats. Adult rats were chronically treated with AlCl3 (100 mg/kg b.w./day) for 60 days to establish the dementia model, and co-administration of CAE was evaluated for its ability to attenuate the toxic effect of AlCl3. CAE was given orally at a dose of 150 and 300 mg/kg b.w./day, for 60 days. The behavioral performances of rats were tested through Y-maze and open field tests. Lipid peroxidation, superoxide dismutase, and catalase activity were evaluated to measure oxidative stress; and acetylcholinesterase (AChE) activity was assessed to evaluate cholinergic dysfunction in the rat brain. H&E staining was used to assess structural abnormalities in the cortex and hippocampus. The result showed that AlCl3 induces cognitive dysfunction (impaired learning and memory, anxiety, diminished locomotor activity), oxidative stress, cholinergic impairment, and histopathological alteration in the rat brain. Co-administration of CAE with AlCl3 markedly protects the brain from AlCl3-induced cognitive dysfunction, oxidative stress, AChE activity, and cytoarchitectural alterations. Furthermore, 15 days CAE treatment after 45 days AlCl3 administration markedly ameliorates the AlCl3-induced neurotoxicity indicating its potential for therapeutic use.

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Acknowledgements

We are thankful to Prof. Kathy W. Nordeen (Brain and Cognitive Sciences, University of Rochester, NY, USA) for her valuable suggestions and for editing the manuscript.

Funding

This work was supported by a fellowship grant to ZF from the Council of Scientific and Industrial Research (CSIR), India.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    Zeba Firdaus & Tryambak Deo Singh

  2. Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, BHU, Varanasi, 221005, India

    Devendra Kumar & Sushil Kumar Singh

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  1. Zeba Firdaus
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  2. Devendra Kumar
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  4. Tryambak Deo Singh
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Contributions

ZF and TDS conceptualized and designed the study and prepared the manuscript. ZF carried the protocol and DY and SKS helped in behavioral and histological studies. All authors read and approve the final manuscript.

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Correspondence to Tryambak Deo Singh.

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This study was approved by the Central Animal Ethical Committee of the Banaras Hindu University (letter number—Dean/2017/CAEC/719, 30.03.2017).

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Firdaus, Z., Kumar, D., Singh, S.K. et al. Centella asiatica Alleviates AlCl3-induced Cognitive Impairment, Oxidative Stress, and Neurodegeneration by Modulating Cholinergic Activity and Oxidative Burden in Rat Brain. Biol Trace Elem Res 200, 5115–5126 (2022). https://doi.org/10.1007/s12011-021-03083-5

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