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Potential of nobiletin against Alzheimer’s disease through inhibiting neuroinflammation

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Abstract

Objective

This study aimed to explore the mechanism of Nobiletin attenuating Alzheimer’s disease (AD) by inhibiting neuroinflammation.

Methods

The expression of inflammatory cytokines and HMGB-1 in serum of AD patients were examined. Microglia (MGs) were treated with different doses of Nobiletin before LPS and Nigericin induction. Cell viability and apoptosis were determined by CCK-8 and TUNEL assays, respectively. APP/PS1 mice were gavaged with Nobiletin, and Morris water maze (MWM) was established to record swimming speed, escape latency, the number of platform crossings, and time spent in the platform quadrant. MGs activation in brain tissues was evaluated by immunofluorescence. The expression of pyroptosis-related proteins, inflammatory cytokines, and HMGB-1 was determined in the hippocampus and MGs.

Results

The levels of inflammatory cytokines and HMGB-1 were high in serum of AD patients. Treatment with different concentrations of Nobiletin prominently enhanced cell viability and reduced apoptosis and the expression of inflammatory cytokine and pyroptosis-related proteins in LPS + Nigericin-induced MGs. Gavage of different doses of Nobiletin into APP/PS1 mice shortened the escape latency in mice, diminished MGs activation in brain tissues, and remarkably elevated the number of platform crossings and the time spent in the platform quadrant without obvious change in swimming speed, suggesting that Nobiletin improved the spatial learning and memory abilities in APP/PS1 mice. The expression of pyroptosis-related proteins, HMGB-1, and inflammatory cytokines was decreased dramatically by Nobiletin in the hippocampus of APP/PS1 mice.

Conclusions

Nobiletin can inhibit neuroinflammation by inhibiting HMGB-1, pyroptosis-related proteins, and inflammatory cytokines, thus mitigating AD.

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Code Availability

Not applicable.

Data Availability

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

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Acknowledgements

Thanks for all the contributors.

Funding

Thanks for the support of the grant from the Natural Science Foundation of Jiangxi Province (Grant No.20202BABL206005 and Grant No.20202BAB216014) and Science and technology plan of Jiangxi Provincial Health Commission (202210013 for Chai Wen).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Nanchang Medical College/Jaingxi Provincial People’s Hospital, No.152, Aiguo Road, 330006, Nanchang, Jiangxi, P.R. China

    Wen Chai, Ji Zhang, Zhengbing Xiang, Honglian Zhang, Zhujun Mei, Hongbing Nie, Renxu Xu & Ping Zhang

  2. Department of General Practice/General Family Medicine, The First Affiliated Hospital of Nanchang Medical College/Jaingxi Provincial People’s Hospital, 330006, Nanchang, Jiangxi, P.R. China

    Renxu Xu

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  1. Wen Chai
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  2. Ji Zhang
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  4. Honglian Zhang
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  7. Renxu Xu
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  8. Ping Zhang
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Contributions

CW conceived the ideas. ZP designed the experiments. XZB performed the experiments. ZHL analyzed the data. CW and ZP provided critical materials. XZB and ZHL wrote the manuscript. MZJ supervised the study. CW, NHB and XRX revised the manuscript. All the authors have read and approved the final version for publication.

Corresponding author

Correspondence to Ping Zhang.

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Ethics approval

This experiment was admitted by the Ethics Committee of Jiangxi provincial People’s Hospital and complied with the Declaration of Helsinki. The study was allowed by the Animal Research and Ethics Committee of Jiangxi provincial People’s Hospital, and all experiments followed the Guide for the Care and Use of Laboratory Animals.

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The author declares they have no competing interest.

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F, forward; R, reverse.

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Chai, W., Zhang, J., Xiang, Z. et al. Potential of nobiletin against Alzheimer’s disease through inhibiting neuroinflammation. Metab Brain Dis 37, 1145–1154 (2022). https://doi.org/10.1007/s11011-022-00932-7

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  • DOI: https://doi.org/10.1007/s11011-022-00932-7

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