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Soursop fruit extract mitigates scopolamine-induced amnesia and oxidative stress via activating cholinergic and Nrf2/HO-1 pathways

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Abstract

Current therapeutic interventions for memory loss are inadequate and are associated with numerous adverse effects. There is an urgent need for new alternative agents for the treatment of memory loss and related disorders. Here, we investigated the potential neuroprotective role of soursop fruit extract (SSFE) in scopolamine (SCO)-induced amnesia and oxidative damage in the hippocampus of rats. Thirty-five rats were randomly allocated into 5 groups: control, SCO, SSFE, SCO, SSFE+SCO and N-acetylcysteine (NAC) + SCO. SCO-treatment increased acetylcholine esterase activity and decreased hippocampal levels of acetylcholine, serotonin, dopamine, norepinephrine, and histamine. The level of ATP increased. SCO-treated rats showed a disturbance in oxidative status, which was evident through the increase in malondialdehyde, and nitrites/nitrates and a decrease in cellular antioxidant molecules including glutathione, superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. A disturbance was also observed via downregulation of the nuclear factor erythroid 2–related factor 2 and heme oxygenase-1 defense pathways. SCO-treatment enhances a neuroinflammatory state, as indicated by the release of tumor necrosis factor- α and interleukin-1β and increased inducible nitric oxide synthase and mRNA expression. SCO-treatment decreased the expression of the anti-apoptotic protein, B cell lymphoma 2 and increased the expression of the pro-apoptotic protein, Bcl-2 associated X protein, caspase-3 and cytochrome c in hippocampal neurons. SSFE pretreatment markedly ameliorated hippocampal changes. Our findings revealed that SSFE exerts its potential anti-amnestic effect mainly through the activation of the cholinergic system and Nrf2/HO-1 pathway.

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Acknowledgements

The authors would like to thank Ton Duc Thang University, Ho Chi Minh City, Vietnam for supporting the current work.

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Correspondence to Ehab Kotb Elmahallawy.

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Al omairi, N.E., Al-Brakati, A.Y., Kassab, R.B. et al. Soursop fruit extract mitigates scopolamine-induced amnesia and oxidative stress via activating cholinergic and Nrf2/HO-1 pathways. Metab Brain Dis 34, 853–864 (2019). https://doi.org/10.1007/s11011-019-00407-2

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  • DOI: https://doi.org/10.1007/s11011-019-00407-2

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