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Sinomenine Attenuates Trimethyltin-Induced Cognitive Decline via Targeting Hippocampal Oxidative Stress and Neuroinflammation

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Abstract

Sinomenine is the main bioactive ingredient of the medicinal plant Sinomenium acutum with neuroprotective potential. This study was designed to assess beneficial effect of sinomenine in alleviation of trimethyltin (TMT)-induced cognitive dysfunction. TMT was administered i.p. (8 mg/kg, once) and sinomenine was daily given p.o. 1 h after TMT for 3 weeks at doses of 25 or 100 mg/kg. Cognitive performance was assessed in various behavioral tests. In addition, oxidative stress- and inflammation-associated factors were measured and histochemical evaluation of the hippocampus was conducted. Sinomenine at a dose of 100 mg/kg significantly and partially increased discrimination index in novel object recognition (NOR), improved alternation in short-term Y maze, increased step-through latency in passive avoidance paradigm, and also reduced probe trial errors and latency in the Barnes maze task. Moreover, sinomenine somewhat prevented inappropriate hippocampal changes of malondialdehyde (MDA), reactive oxygen species (ROS), protein carbonyl, nitrite, superoxide dismutase (SOD), tumor necrosis factor α (TNFα), interleukin 6 (IL 6), acetylcholinesterase (AChE) activity, beta secretase 1 (BACE 1) activity, and mitochondrial membrane potential (MMP) with no significant effect on glutathione (GSH), catalase, glutathione reductase, glutathione peroxidase, and myeloperoxidase (MPO). In addition, lower reactivity (IRA) for glial fibrillary acidic protein (GFAP) as an index of astrocyte activity was observed and loss of CA1 pyramidal neurons was attenuated following sinomenine treatment. This study demonstrated that sinomenine could lessen TMT-induced cognitive dysfunction which is partly due to its attenuation of hippocampal oxidative stress and neuroinflammation.

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Data Availability

Data generated and analyzed during the present study will be available from the corresponding author on reasonable request.

Abbreviations

AChE:

Acetylcholinesterase

AD:

Alzheimer’s disease

BACE 1:

Beta secretase 1

GFAP:

Glial fibrillary acidic protein

GSH:

Reduced Glutathione

IL-6:

Interleukin 6

MDA:

Malondialdehyde

MMP:

Mitochondrial membrane potential

MPO:

Myeloperoxidase

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NOD:

Novel object discrimination

Nrf2:

Nuclear factor erythroid 2-related factor 2

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TMT:

Trimethyltin

TNFα:

Tumor necrosis factor α

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Funding

This research project was financially supported in 2021 by National Institute for Medical Research Development (NIMAD) (grant number 996144).

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Authors and Affiliations

  1. School of Medicine, Shahed University, Tehran, Iran

    Amir Rostami

  2. Department of Physiology, School of Medicine, Shahed University, Tehran, Iran

    Fatemeh Taleahmad & Narges Haddadzadeh-Niri

  3. Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran

    Ensiye Joneidi

  4. Neurophysiology Research Center, Shahed University, Tehran, Iran

    Siamak Afshin-Majd & Mehrdad Roghani

  5. Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Tourandokht Baluchnejadmojarad

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  1. Amir Rostami
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  2. Fatemeh Taleahmad
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Contributions

A.R., F.T., N.H, and E.J. performed experiments and helped in manuscript writing. M.R., S.A.M., and T.B. designed the study and protocol of experiments, supervised conductance of experiments, and wrote the manuscript. MR. performed statistical analysis of data.

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Correspondence to Mehrdad Roghani.

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All experimental procedures of this study were conducted under ethics committee supervision of NIMAD (# IR.NIMAD.REC.1399.286) that was in accordance to NIH guidelines for the care and use of laboratory animals. All efforts were made to minimize number of animals and to lower their sufferings.

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Rostami, A., Taleahmad, F., Haddadzadeh-Niri, N. et al. Sinomenine Attenuates Trimethyltin-Induced Cognitive Decline via Targeting Hippocampal Oxidative Stress and Neuroinflammation. J Mol Neurosci 72, 1609–1621 (2022). https://doi.org/10.1007/s12031-022-02021-x

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