St. John's wort and its component hyperforin alleviate experimental autoimmune encephalomyelitis through expansion of regulatory T-cells

J Immunotoxicol. 2016 May;13(3):364-74. doi: 10.3109/1547691X.2015.1101512. Epub 2015 Dec 3.

Abstract

Multiple sclerosis (MS) is a central nervous system disorder mainly characterized by inflammation, demyelination and axonal injury. Anti-inflammatory agents can be used to ameliorate the disease process. Hypericum perforatum L or St. John's wort is widely used as an anti-depressant and anti-inflammatory remedy in traditional and herbal medicine. Based on St. John's wort properties, the therapeutic potentials of an H. perforatum extract (HPE) and a single component, hyperforin were evaluated for effectiveness against MOG35-55-induced experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Female C57BL/6 mice were immunized with specific antigen MOG35-55 and then administered different doses of hyperforin or HPE post-immunization. Clinical symptoms/other relevant parameters were assessed daily. Histological analysis of the spinal cord was performed. T-cell proliferative activity was also evaluated using a BrdU assay. The effect of hyperforin on regulatory T-cells (Treg cells) was assessed using flow cytometry. The results indicate hyperforin and HPE reduced the incidence and severity of EAE, an outcome that closely correlated with an inhibition of pathological features (leukocyte infiltration and demyelination) and antigen-specific T-cell proliferation. The study also showed that hyperforin caused increased Treg cell levels in the spleen. These results indicated that hyperforin and HPE could attenuate EAE autoimmune responses by inhibiting immune cell infiltration and expansion of Treg cell and could eventually be considered as a potential candidate for use in the treatment of MS.

Keywords: Experimental autoimmune encephalomyelitis (EAE); Hypericum perforatum L; hyperforin; multiple sclerosis; myelin oligodendrocyte glycoprotein (MOG).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Female
  • Humans
  • Hypericum / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / therapy*
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Peptide Fragments / immunology
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / immunology
  • Phloroglucinol / therapeutic use
  • Phytotherapy*
  • Spleen / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Terpenes / immunology*
  • Terpenes / therapeutic use

Substances

  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Terpenes
  • myelin oligodendrocyte glycoprotein (35-55)
  • Phloroglucinol
  • hyperforin