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Matrine Mediated Immune Protection in MS by Regulating Gut Microbiota and Production of SCFAs

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Abstract

There is clearly an unmet need for more effective and safer treatments for multiple sclerosis (MS). Our previous studies showed a significant therapeutic effect of matrine, a monomer of traditional herbal medicine, on experimental autoimmune encephalomyelitis (EAE) mice. To explore the mechanism of matrine action, we used 16S rRNA sequencing technology to determine the gut microbes in matrine-treated EAE mice and controls. The concentrations of short-chain fatty acids (SCFAs) were then tested by metabonomics. Finally, we established pseudo-sterile mice and transplanted into them fecal microbiota, which had been obtained from the high-dose matrine-treated EAE mice to test the effects of matrine. The results showed that matrine could restore the diversity of gut microbiota and promote the production of SCFAs in EAE mice. Transplantation of fecal microbiota from matrine-treated mice significantly alleviated EAE severity, reduced CNS inflammatory infiltration and demyelination, and decreased the level of IL-17 but increased IL-10 in sera of mice. In conclusion, matrine treatment can regulate gut microbiota and metabolites and halt the progression of MS.

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Data Availability

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

Abbreviations

ABX :

Non-absorbable antibiotics

ANOSIM :

Analysis of similarities

CBA :

Cytometric bead assay

CFA :

Complete Freund’s adjuvant

CNS :

The central nervous system

DMTs :

Disease-modifying therapies

EAE :

Experimental autoimmune encephalomyelitis

FMT :

Fecal microbiological transplantation

MAT :

Matrine

MS :

Multiple sclerosis

NMDS :

Multidimensional scaling

PCA :

Principal component analysis

PCoA :

Principal coordinates analysis

SAA :

Serum amyloid A

SCFAs :

Short chain fatty acids

SFB :

Segmented filamentous bacteria

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Acknowledgements

We thank Mrs. Katherine Regan and Dr. Mobin Siddiqui for their editorial assistance.

Funding

This research was supported by the National Natural Science Foundation of China (No. 31870334), the Key Research and Promotion Project of Henan Province (No. 222102310346), the Provincial and Ministerial Key Project of Henan Medical Science and Technology Research Plan (No. SBGJ202102087), and the Key Scientific Research Projects of Colleges and Universities in Henan Province (No. 22A350018).

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  1. Mengmeng Dou, Yaojuan Chu, and Xueliang Zhou contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Mengmeng Dou, Yaojuan Chu, Xinyu Li, Rui Ma, Xiaoyu Zhao, Wenbin Wang, Silu Li, Ying Lv & Lin Zhu

  2. Department of Integrated Traditional and Western Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Mengmeng Dou & Zhirui Fan

  3. Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Xueliang Zhou

  4. Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China

    Mengru Wang

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  1. Mengmeng Dou
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Contributions

Mengmeng Dou, Yaojuan Chu, Xueliang Zhou, and Lin Zhu participated in the study conceptualization and experimental design. Mengmeng Dou, Yaojuan Chu, Xueliang Zhou, Mengru Wang, Xinyu Li, and Rui Ma performed the experiments. Mengmeng Dou, Yaojuan Chu, Xiaoyu Zhao, Wenbin Wang, and Silu Li analyzed the data. Mengmeng Dou, Yaojuan Chu, and Xueliang Zhou wrote the manuscript. Zhirui Fan and Ying Lv contributed key materials for experiments.

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Correspondence to Lin Zhu.

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Dou, M., Chu, Y., Zhou, X. et al. Matrine Mediated Immune Protection in MS by Regulating Gut Microbiota and Production of SCFAs. Mol Neurobiol 61, 74–90 (2024). https://doi.org/10.1007/s12035-023-03568-5

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