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Research Article

Europinidin Attenuates Methamphetamine-induced Learning and Memory Impairments and Hippocampal Alterations in Rodents: Based on Molecular Docking through a Mechanism of Neuromodulatory Cytokines/ Caspases-3/ CREB/BDNF Pathway

Author(s):

Ryan A. Sheikh, Muhammad Afzal, Fahad A. Al-Abbasi, Hussam A. Bukhari, Naif A. R. Almalki, May M. Alqurashi, Faisal Imam, Nadeem Sayyed and Imran Kazmi*   Pages 1 - 19 ( 19 )

Abstract:


Background: Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally.

Objective: The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. This was achieved by inhibiting lipid peroxidation and pro-inflammatory markers.

Methods: Rats were exposed to cognitive impairment produced by MA. The Morris water maze (MWM) is utilized for evaluating behavioral parameters. Tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1β (IL-1β), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets.

Results: Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1β, CREB, TNF-α, BDNF, and Caspase 3 proteins expression, as well as considerably alterations in level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol.

Conclusion: The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.

Keywords:

Neuroinflammatory cytokines, europinidin, neuroprotective, oxidative stress, methamphetamine.

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