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Piperine Improves Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats Through its Neuroprotective, Anti-inflammatory, and Antioxidant Effects

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Abstract

Inflammation, demyelination, glial activation, and oxidative damage are the most pathological hallmarks of multiple sclerosis (MS). Piperine, a main bioactive alkaloid of black pepper, possesses antioxidant, anti-inflammatory, and neuroprotective properties whose therapeutic potential has been less studied in the experimental autoimmune encephalomyelitis (EAE) models. In this study, the efficiency of piperine on progression of EAE model and myelin repair mechanisms was investigated. EAE was induced in female Lewis rats and piperine and its vehicle were daily administrated intraperitoneally from day 8 to 29 post immunization. We found that piperine alleviated neurological deficits and EAE disease progression. Luxol fast blue and H&E staining and immunostaining of lumbar spinal cord cross sections confirmed that piperine significantly reduced the extent of demyelination, inflammation, immune cell infiltration, microglia, and astrocyte activation. Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-inflammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf2, HO-1, and MBP expressions. Piperine supplementation also enhanced the total antioxidant capacity (FRAP) and reduced the level of oxidative stress marker (MDA) in the CNS of EAE rats. Finally, we found that piperine has anti-apoptotic and neuroprotective effect in EAE through reducing caspase-3 (apoptosis marker) and enhancing BDNF and NeuN expressing cells. This study strongly indicates that piperine has a beneficial effect on the EAE progression and could be considered as a potential therapeutic target for MS treatment. Upcoming clinical trials will provide a deeper understanding of piperine’s role for the treatment of the MS.

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

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Acknowledgements

The authors would like to gratefully appreciate the kind support of Dr. Mohammad Javan from physiology department of Tarbiat Modares University Tehran-Iran and technical assistance of Mrs. Atena Nazari during the study.

Funding

This work was supported by a grant from the Deputy of Research and Technology (No. 724132502), Babol University of Medical Sciences, Babol, Iran, and was performed as a part of Master of Science thesis in Clinical Biochemistry in the Physiology and Biochemistry Departments at Babol University of Medical Sciences.

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Authors and Affiliations

  1. Student Research Committee, Babol University of Medical Sciences, Babol, Iran

    Reza Nasrnezhad

  2. Department of Biochemistry, School of Medicine, Babol University of Medical Sciences, Babol, Iran

    Reza Nasrnezhad & Sohrab Halalkhor

  3. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

    Farzin Sadeghi & Fereshteh Pourabdolhossein

  4. Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran

    Fereshteh Pourabdolhossein

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  1. Reza Nasrnezhad
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  2. Sohrab Halalkhor
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  4. Fereshteh Pourabdolhossein
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by Reza Nasrnezhad, Sohrab Halalkhor, and Fereshteh Pourabdolhossein. Data analysis and interpretation was done by Reza Nasrnezhad, Farzin Sadeghi, and Fereshteh Pourabdolhossein. The first draft of the manuscript was written by Reza Nasrnezhad and its major revision was performed by Fereshteh Pourabdolhossein. All authors read and approved the final manuscript.

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Correspondence to Fereshteh Pourabdolhossein.

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All experimental procedures of this study were conducted according to the international guidelines for care and use of laboratory animals and approved (Ethic code number: IR.MUBABOL.HRI.REC.1398.315) by the ethical committee of Babol University of Medical Sciences.

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It is not applicable in our study because this article does not contain any studies involving human participants performed by any of the authors.

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Nasrnezhad, R., Halalkhor, S., Sadeghi, F. et al. Piperine Improves Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats Through its Neuroprotective, Anti-inflammatory, and Antioxidant Effects. Mol Neurobiol 58, 5473–5493 (2021). https://doi.org/10.1007/s12035-021-02497-5

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