4.6 Article

Cornuside alleviates experimental autoimmune encephalomyelitis by inhibiting Th17 cell infiltration into the central nervous system

Journal

JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
Volume 22, Issue 5, Pages 421-430

Publisher

ZHEJIANG UNIV
DOI: 10.1631/jzus.B2000771

Keywords

Cornuside; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Inflammation

Funding

  1. Traditional Chinese Medical Science and Technology Project of Zhejiang Province [2019ZA063]
  2. Scientific Research Fund of Zhejiang Chinese Medical University [2019ZY09]

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The study investigated the therapeutic effects of cornuside on EAE and its impact on Th17 and Treg cell infiltration. Cornuside showed anti-inflammatory and immunosuppressive effects, alleviating neurological deficits in EAE rats with Th17 cells possibly being one of its therapeutic targets.
The present study was conducted to clarify the therapeutic effect of cornuside on experimental autoimmune encephalomyelitis (EAE) and its influence on T helper 17 (Th17) cell and regulatory T (Treg) cell infiltration into the central nervous system. Rats were randomly placed into four treatment groups: control, EAE, EAE+cornuside, and EAE+prednisolone. The neurological function scores of rats were assessed daily. On the second day after EAE rats began to show neurological deficit symptoms, the four groups were treated with normal saline, normal saline, cornuside (150 mg/kg), and prednisolone (5 mg/kg), respectively. The treatment was discontinued after two weeks, and the spinal cord was obtained for hematoxylin and eosin (H&E) and luxol fast blue staining, as well as retinoic acid receptor-related orphan receptor gamma (ROR gamma) and forkhead box protein P3 (Foxp3) immunohistochemical staining. Blood was collected for Th17 and Treg cell flow cytometry testing, and the serum levels of interleukin (IL)-17A, IL-10, transforming growth factor-beta (TGF-beta), IL-6, IL-23, and IL-2 were measured via enzyme-linked immunosorbent assay (ELISA). Compared with rats in the EAE group, rats in the EAE+cornuside and EAE+prednisolone groups began to recover from neurological deficits earlier, and had a greater degree of improvement of symptoms. Focal inflammation, demyelination, and ROR gamma-positive cell infiltration were reduced by cornuside or prednisolone treatment, whereas the Foxp3-positive cell numbers were not significantly different. Meanwhile, the number of Th17 cells and the IL-17A, IL-6, and IL-23 levels were lower in the blood after cornuside or prednisolone treatment, whereas the number of Treg cells or the levels of IL-10, TGF-beta, and IL-2 were not markedly different. Cornuside can alleviate symptoms of EAE neurological deficits through its anti-inflammatory and immunosuppressive effects, and Th17 cells may be one of its therapeutic targets.

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