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RETRACTED ARTICLE: Magnolol prevented brain injury through the modulation of Nrf2-dependent oxidative stress and apoptosis in PLP-induced mouse model of multiple sclerosis

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Abstract

Multiple sclerosis (MS) is an immune-mediated chronic inflammatory demyelinating disease of the central nervous system (CNS). The aim of the current study was to investigate the effects of magnolol in an experimental autoimmune encephalomyelitis (EAE) model of MS in female mice. Magnolol (0.1, 1, and 10 mg/kg) was administered once daily for 21 days after immunization of mice. Magnolol post-immunization treatment significantly reversed clinical scoring, EAE-associated pain parameters, and motor dysfunction in a dose-dependent manner. Magnolol treatment significantly inhibited oxidative stress by reducing malondialdehyde (MDA), nitric oxide (NO) production, and myeloperoxidase (MPO) activity while enhancing the level of antioxidants such as reduced glutathione (GSH), glutathione-S-transferase (GST), catalase, and superoxide dismutase (SOD) in the brain and spinal cord. It reduced cytokine levels in the brain and spinal cord. It suppressed CD8+ T cells frequency in the spleen tissue. Magnolol remarkably reversed the EAE-associated histopathology of the brain and spinal cord tissue. Magnolol significantly intensifies the antioxidant defense system by enhancing the expression level of nuclear factor erythroid 2-related factor (Nrf2) while decreasing the expression of inducible nitric oxide synthase (iNOS) and cleaved-caspase-3 in the brain. Molecular docking results showed that magnolol possesses a better binding affinity for Nrf2, iNOS, and caspase-3 proteins. Taken together, the present study demonstrated that magnolol has significant neuroprotective properties in EAE via inhibition of oxidative stress.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. NRF-2021R1A2C1003350).

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The authors declare that all the data were generated in-house and that no paper mill was used. TB and AK designed and performed the research including behavioral and biochemical assays. AUK and BS helped in the behavioral and biochemical assays. AK and TB wrote the original manuscript. TB, AK, AUK, BS, HA, EKS, and SK analyzed the data and drafted the manuscript. SK and EKS supervised the project. All the authors read and approved the manuscript.

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Correspondence to Eun Kyoung Seo or Salman Khan.

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“National Institutes of Health (NIH) guidelines for animal care” were followed for the animals’ experimentation. Quaid-i-Azam University, Islamabad Bioethical Committee (Approval No: BEC-FBS QAU2019-179) approved the study. Maximum care was made to minimize harm to animals.

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Bibi, T., Khan, A., Khan, A.U. et al. RETRACTED ARTICLE: Magnolol prevented brain injury through the modulation of Nrf2-dependent oxidative stress and apoptosis in PLP-induced mouse model of multiple sclerosis. Naunyn-Schmiedeberg's Arch Pharmacol 395, 717–733 (2022). https://doi.org/10.1007/s00210-022-02230-6

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