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9,10-Anhydrodehydroartemisinin Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Th1 and Th17 Cell Differentiation

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Abstract

Human inflammatory disease, multiple sclerosis (MS), is a demyelinating disease of central nervous system (CNS). The experimental autoimmune encephalomyelitis (EAE) is the most commonly used as experimental model because of its key pathological features’ approximation of MS. The interaction between complex elements in immune system and in the CNS determines the MS pathogenesis. However, there is no cure for MS and the treatment for MS still encounters great challenges. Thus, finding a more effective disease-modifying treatment is imminent. In the present study, we investigated whether 9,10-Anhydrodehydroartemisin (ADART), a compound derived from artemisinin, could decrease demyelination in EAE and the underlying mechanisms. In established EAE mice, 100 mg/kg 9,10-Anhydrodehydroartemisinin (ADART) effectively reduced CNS and peripheral immune system infiltration inflammatory cells including CD4+ IFN-γ+ Th1 cells and CD4+ IL-17A+ Th17 cells. Correspondingly, the serum level of IFN-γ and IL-17A was also reduced. In vitro, ADART almost completely inhibited Th17 differentiation, and partially inhibited Th1 differentiation in 10 μM. This research revealed that ADART could be a great promising avenue among current therapies for MS.

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The data used to support the findings of this study are included in the article.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (32070768, 31871404, 31900658), the Special Foundation of Chinese Academy of Sciences for strategic pilot technology (XDA12040327), Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01), and the State Key Laboratory of Drug Research.

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Author notes

  1. Jie Lv, Wei Zhuang, and Yan Zhang contributed equally to this work.

Authors and Affiliations

  1. Putuo People’s Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China

    Jie Lv, Wei Zhuang, Ling Xie, Zhenglong Xiang & Changsheng Du

  2. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Wei Zhuang

  3. University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China

    Wei Zhuang, Xiangrui Jiang & Jingshan Shen

  4. Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 40-1 Beijing Road, Urumqi, 830011, Xinjiang, China

    Yan Zhang

  5. CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China

    Qingjie Zhao & Xiangrui Jiang

  6. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China

    Jingshan Shen & Changsheng Du

Authors
  1. Jie Lv
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  2. Wei Zhuang
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  3. Yan Zhang
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  4. Ling Xie
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  5. Zhenglong Xiang
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  9. Changsheng Du
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Contributions

Design and experimentation: J.L., W.Z., X.J., L.X., Z.L., Q.Z., and Y.Z.; supervision: C.D. and J.S.; and manuscript writing: W.Z. and C.D.

Corresponding authors

Correspondence to Xiangrui Jiang or Changsheng Du.

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All experiment procedures were approved and carried out in accordance with the Tongji University Animal Care Committee guidelines.

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Not applicable.

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The authors declare no competing interests.

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Lv, J., Zhuang, W., Zhang, Y. et al. 9,10-Anhydrodehydroartemisinin Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Th1 and Th17 Cell Differentiation. Inflammation 44, 1793–1802 (2021). https://doi.org/10.1007/s10753-021-01456-5

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  • DOI: https://doi.org/10.1007/s10753-021-01456-5

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