Herpetol ameliorates allergic contact dermatitis through regulating T-lymphocytes

Int Immunopharmacol. 2016 Nov:40:131-138. doi: 10.1016/j.intimp.2016.08.025. Epub 2016 Aug 31.

Abstract

An immunosuppressant with fewer adverse effects is still urgently needed for increasing numbers of patients suffering from allergic contact dermatitis. In the present study, we aimed to investigate the immunosuppressive activity of herpetol on T-lymphocytes in vitro and in vivo and explore its potential pharmacological mechanism. The results showed that herpetol could effectively inhibit the proliferation of activated T cells and reduce the production of pro-inflammatory cytokines at 5-20μM. Additionally, the ear swelling and inflammatory responses induced by picryl chloride were significantly ameliorated by herpetol at 20-40mg/kg. Moreover, herpetol could cause cell cycle arrest of activated T cells in a dose-dependent manner. Furthermore, herpetol reduced the expression and activity of HIF-1α, Glut1 and LDHA, leading to glycolysis inhibition in activated T cells. Taken together, herpetol showed an immunosuppressive activity against T-cell mediated immune responses in vitro and in vivo, and it has potential for the treatment of immune-related skin diseases.

Keywords: Allergic contact dermatitis; Drug candidate; Glycolysis; Herpetol; T-lymphocytes.

MeSH terms

  • Animals
  • Benzofurans / pharmacology*
  • Benzofurans / therapeutic use*
  • Cell Cycle / drug effects
  • Dermatitis, Allergic Contact / drug therapy*
  • Dermatitis, Allergic Contact / immunology
  • Dermatitis, Allergic Contact / pathology
  • Ear / pathology
  • Female
  • Glucose Transporter Type 1 / genetics
  • Glycolysis / drug effects
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use*
  • Lymph Nodes / cytology
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Picryl Chloride
  • Spleen / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Benzofurans
  • Glucose Transporter Type 1
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunosuppressive Agents
  • Slc2a1 protein, mouse
  • herpetol
  • Picryl Chloride