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Voglibose attenuates cognitive impairment, Aβ aggregation, oxidative stress, and neuroinflammation in streptozotocin-induced Alzheimer’s disease rat model

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Abstract

Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease hallmarked by Amyloid-β (Aβ) aggregation, cognitive impairment, and neuronal and synaptic loss. In this study, AD was induced in male Wistar rats (n = 6) by the administration of intracerebroventricular-streptozotocin (ICV-STZ-3 mg/kg/day), and Voglibose (Vog) was administered at various doses (10, 25, and 50 mg/kg), while Galantamine (3 mg/kg) acted as a reference standard drug. Behavioral alterations in both spatial and non-spatial memory functions were evaluated in the experimental rats. At the end of the study, all experimental rats were sacrificed, and their brain parts, the cortex and hippocampus, were subjected to biochemical, western blot, and histopathological analysis. In our study results, the statistically significant dose-dependent results from the behavioral tests show the Voglibose-treated groups significantly improved (p < 0.0001) spatial and non-spatial memory functions when compared with ICV-STZ-treated group. Meanwhile, when compared with ICV-STZ-treated rats, treatment with Voglibose (10, 25, and 50 mg/kg) showed the activities of both acetylcholinesterase (AChE) and malondialdehyde (MDA) were significantly attenuated (p < 0.0001), while the operation of antioxidant enzymes was considerably enhanced (p < 0.0001). The molecular estimation showed that it significantly attenuates (p < 0.0001) the TNF-α, IL-1β, and CRP activity, and the western blot results demonstrate the significantly attenuated Aβ aggregation. The histopathological results showed that the Voglibose treatment had an effective improvement in clear cytoplasm and healthy neuronal cells. In conclusion, our results suggest that Voglibose has potent neuroprotective effects against the ICV-STZ-induced AD model. Furthermore, these results support the possibility of Voglibose as a therapeutic approach to improving cognitive function, suggesting that controlling Aβ aggregation might be a novel target for the development of AD.

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Acknowledgements

This work was financially supported by University Research Fellow (URF) from Periyar University, Salem 636011, 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, Tamil Nadu, 636 011, India

    Manickam Rajkumar & Soundarapandian Kannan

  2. Department of Zoology, Periyar University, Salem, Tamil Nadu, 636 011, India

    Ramasundaram Thangaraj

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  1. Manickam Rajkumar
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  2. Soundarapandian Kannan
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Correspondence to Soundarapandian Kannan.

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Rajkumar, M., Kannan, S. & Thangaraj, R. Voglibose attenuates cognitive impairment, Aβ aggregation, oxidative stress, and neuroinflammation in streptozotocin-induced Alzheimer’s disease rat model. Inflammopharmacol 31, 2751–2771 (2023). https://doi.org/10.1007/s10787-023-01313-x

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