Indirubin, a purple 3,2- bisindole, inhibited allergic contact dermatitis via regulating T helper (Th)-mediated immune system in DNCB-induced model

J Ethnopharmacol. 2013 Jan 9;145(1):214-9. doi: 10.1016/j.jep.2012.10.055. Epub 2012 Nov 10.

Abstract

Ethnopharmacological relevance: Indirubin, isolated from Indigo naturalis (Apiaceae) is a purple 3,2- bisindole and a stable isomer of indigo. Although it is known to have anti-inflammatory activities, its mechanism of action has not been elucidated.

Materials and methods: Seven-week-old female BALB/c mice were sensitized with 1-chloro-2,4-dinitrobenzene (DNCB) to induce skin inflammation. Hematoxylin and eosin staining was performed to assess epidermal and dermal hyperplasia, which were determined by measuring the thicknesses of the epidermis and dermis, respectively. We also evaluated serum immunoglobulin E (IgE) levels and cytokines production, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, 6 and Interferon (IFN)-gamma. In addition, we investigated nuclear factor (NF)-κB, IκB-α and mitogen-activated protein (MAP) kinase activities for verifying the molecular mechanism of inflammation.

Results: Indirubin treatment suppressed skin inflammation in DNCB-exposed mice. The skin lesions were significantly thinner in the Indirubin-treated group than in untreated controls, and the hyperkeratosis disappeared. Indirubin reduced the total serum IgE level and cytokines production. In addition, it normalized NF-κB, IκB-α and MAP kinase expression.

Conclusions: Indirubin might be a useful treatment for allergic contact dermatitis via regulating the co-expression of T helper (Th) 1 and 2 cell-mediated immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cytokines / metabolism
  • Dermatitis, Allergic Contact / blood
  • Dermatitis, Allergic Contact / drug therapy*
  • Dermatitis, Allergic Contact / pathology
  • Dinitrochlorobenzene
  • Disease Models, Animal
  • Female
  • Hyperplasia / chemically induced
  • Hyperplasia / pathology
  • I-kappa B Proteins / metabolism
  • Immune System / drug effects*
  • Immune System / metabolism
  • Immunoglobulin E / metabolism
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Dinitrochlorobenzene
  • I-kappa B Proteins
  • Indoles
  • NF-kappa B
  • Immunoglobulin E
  • Mitogen-Activated Protein Kinases
  • indirubin