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

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Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-beta (Aβ) aggregation, neuroinflammation, oxidative stress, and dysfunction in the mitochondria and cholinergic system. In this study, the synthesis of chitosan-polylactic acid-loaded magnesium oxide nanocomposite (CH/PLA/MgONCs) was examined using the green precipitation method. The synthesized CH/PLA/MgONCs were confirmed by using the UV–Vis spectrum, FT-IR, SEM-EDAX, and physical properties. The experiments were carried out using male Wistar rats by injecting streptozotocin (STZ) bilaterally into the brain's ventricles through the intracerebroventricular (ICV) route at a dose of 3 mg/kg. We also evaluated the effects of CH/PLA/MgONCs at doses of 10 mg/kg. To assess the cognitive dysfunction induced by ICV-STZ, we performed behavioral, biochemical, and histopathological analyses. In our study results, UV–Vis spectrum analysis of CH/PLA/MgONCs showed 285 nm, FT-IR analyses confirmed that the various functional groups were present, and SEM-EDAX analysis confirmed that a cauliflower-like spherical shape, Mg and O were present. Treatment with CH/PLA/MgONCs (10 mg/kg) showed a significant improvement in spatial and non-spatial memory functions. This was further supported by biochemical analysis showing improved antioxidant enzyme (GSH, SOD, CAT, and GPx activity) activities that significantly attenuated cholinergic activity and oxidative stress. In the CH/PLA/MgONCs-treated group, significant improvement was observed in the mitochondrial complex activity. ICV-STZ-induced neuroinflammation, as indicated by increased levels of TNF-α, IL-6, and CRP, was significantly reduced by CH/PLA/MgONCs treatment. Additionally, CH/PLA/MgONCs treated histological results showed improved healthy neuronal cells in the brain. Furthermore, in silico studies confirm that these molecules have good binding affinity and inhibit Aβ aggregation. In conclusion, CH/PLA/MgONCs treatment reversed AD pathology by improving memory and reducing oxidative stress, neuroinflammation, and mitochondrial dysfunction. These findings recommend that CH/PLA/MgONCs are possible therapeutic agents to treat AD.

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Funding

This work was financially supported and received from the University Research Fellow (URF) from Periyar University, Salem-636 011, Tamil Nadu, India (PU/AD-3/URF/013805/2019).

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Authors and Affiliations

  1. Cancer Nanomedicine Laboratory, Department of Zoology, School of Life Sciences, Periyar University, Salem, 636 011, Tamil Nadu, India

    Manickam Rajkumar, Karuppaiya Vimala & Soundarapandian Kannan

  2. Department of Chemistry, St. Joseph’s Institute of Technology, Chennai, 600 119, Tamil Nadu, India

    Prabha Govindaraj

  3. Vermitechnology and Ecotoxicology Laboratory, Department of Zoology, School of Life Sciences, Periyar University, Salem, 636 011, Tamil Nadu, India

    Ramasundaram Thangaraj

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  1. Manickam Rajkumar
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All authors performed the literature research, analyzed, and critically discussed the data. The authors also contributed to elaborating the figures and approving the final version of the manuscript.

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Rajkumar, M., Govindaraj, P., Vimala, K. et al. Chitosan/PLA-loaded Magnesium oxide nanocomposite to attenuate oxidative stress, neuroinflammation and neurotoxicity in rat models of Alzheimer's disease. Metab Brain Dis 39, 487–508 (2024). https://doi.org/10.1007/s11011-023-01336-x

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