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Molecular Neurobiology

, Volume 53, Issue 8, pp 5356–5366 | Cite as

Arctigenin Suppress Th17 Cells and Ameliorates Experimental Autoimmune Encephalomyelitis Through AMPK and PPAR-γ/ROR-γt Signaling

  • Wen Li
  • Zhihui Zhang
  • Kai Zhang
  • Zhenyi Xue
  • Yan Li
  • Zimu Zhang
  • Lijuan Zhang
  • Chao Gu
  • Qi Zhang
  • Junwei Hao
  • Yurong Da
  • Zhi Yao
  • Ying KongEmail author
  • Rongxin ZhangEmail author
Article

Abstract

Arctigenin is a herb compound extract from Arctium lappa and is reported to exhibit pharmacological properties, including neuronal protection and antidiabetic, antitumor, and antioxidant properties. However, the effects of arctigenin on autoimmune inflammatory diseases of the CNS, multiple sclerosis (MS), and its animal model experimental autoimmune encephalomyelitis (EAE) are still unclear. In this study, we demonstrated that arctigenin-treated mice are resistant to EAE; the clinical scores of arctigenin-treated mice are significantly reduced. Histochemical assays of spinal cord sections also showed that arctigenin reduces inflammation and demyelination in mice with EAE. Furthermore, the Th1 and Th17 cells in peripheral immune organs are inhibited by arctigenin in vivo. In addition, the Th1 cytokine IFN-γ and transcription factor T-bet, as well as the Th17 cytokines IL-17A, IL-17F, and transcription factor ROR-γt are significantly suppressed upon arctigenin treatment in vitro and in vivo. Interestedly, Th17 cells are obviously inhibited in CNS of mice with EAE, while Th1 cells do not significantly change. Besides, arctigenin significantly restrains the differentiation of Th17 cells. We further demonstrate that arctigenin activates AMPK and inhibits phosphorylated p38, in addition, upregulates PPAR-γ, and finally suppresses ROR-γt. These findings suggest that arctigenin may have anti-inflammatory and immunosuppressive properties via inhibiting Th17 cells, indicating that it could be a potential therapeutic drug for multiple sclerosis or other autoimmune inflammatory diseases.

Keywords

Arctigenin Th17 cells Experimental autoimmune encephalomyelitis AMPK PPAR-γ 

Abbreviations

MS

Multiple sclerosis

EAE

Experimental autoimmune encephalomyelitis

MOG

Myelin oligodendrocyte glycoprotein

CNS

Central nervous system

H&E

Hematoxylin-eosin

IL-1β

Interleukin-1β

IL-4

Interleukin-4

IL-6

Interleukin-6

IL-17A

Interleukin-17A

IL-17F

Interleukin-17F

IFN-γ

Interferon-γ

TNF-α

Tumor necrosis factor-α

TGF-β

Transforming growth factor-β

PPAR-γ

Peroxisome proliferator-activated receptor-γ

ROR-γt

Retinoidrelated orphan receptor-γt

MAPK

Mitogen-activated protein kinases

AMPK

Adenosine 5′-monophosphate (AMP)-activated protein kinase

Notes

Acknowledgments

This work is supported by the Ministry of Science and Technology of China through Grants No 2012CB932503 and 2011CB933100, the National Natural Science Foundation of China through Grants No 81172864, 81272317, 81302568, 81301026, and 31570798, and the grant TD12-5025. Natural Science Foundation of Tianjin through Grant No. 14JCTPJC00487. Tianjin Innovative grant in Nanomedicine.

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Wen Li
    • 1
  • Zhihui Zhang
    • 1
  • Kai Zhang
    • 1
  • Zhenyi Xue
    • 1
  • Yan Li
    • 1
  • Zimu Zhang
    • 1
  • Lijuan Zhang
    • 1
  • Chao Gu
    • 1
  • Qi Zhang
    • 1
  • Junwei Hao
    • 2
  • Yurong Da
    • 1
  • Zhi Yao
    • 1
  • Ying Kong
    • 3
    Email author
  • Rongxin Zhang
    • 1
    Email author
  1. 1.Laboratory of Immunology and Inflammation, Department of Immunology and Research Center of Basic Medical Sciences, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironments and Diseases of Educational Ministry, Key Laboratory of Hormones and Development (Ministry of Health)Tianjin Medical UniversityTianjinChina
  2. 2.Department of Neurology, Tianjin Neurological InstituteTianjin Medical University General HospitalTianjinChina
  3. 3.Department of Biochemistry and MolecularDalian Medical UniversityDalianChina

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