Dang-Gui-Liu-Huang Tang a traditional herbal formula, ameliorates imiquimod-induced psoriasis-like skin inflammation in mice by inhibiting IL-22 production

Phytomedicine. 2018 Aug 1;47:48-57. doi: 10.1016/j.phymed.2018.04.051. Epub 2018 May 9.

Abstract

Background: The traditional herbal formula, Dang-Gui-Liu-Huang Tang (DGLHT) has been previously shown to inhibit T lymphocyte proliferation and suppress dendritic cell function. Hypothesis/Purpose: To assess the therapeutic value of DGLHT for the treatment of psoriasis, a Th1 and/or Th17 cell-mediated inflammatory skin disease, and to investigate the underlying molecular mechanisms.

Methods: An in vivo mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation was used to investigate the effect of DGLHT. The anti-inflammatory effects of an ethanolic extract of DGLHT (DGLHT-E) and the mechanism responsible were examined in an in vitro model using IL-1α, IL-17A, IL-22, oncostatin M, plus TNF-α (M5) stimulated HaCaT cells. The anti-proliferative effect of DGLHT-E was examined by analyzing the expression levels of K16, K17 and Ki67 in IL-22 stimulated HaCaT cells.

Results: Topical application of 1% DGLHT-E significantly reduced psoriasis-like symptoms including scaling and epidermal hyperplasia in IMQ-treated mice. Immunohistochemical studies showed that DGLHT-E exerted potent anti-inflammatory effects by inhibiting IL-22 production in local skin lesions. DGLHT-E also attenuated the productions of CXCL10 and CCL20 in M5-stimulated HaCaT cells by suppressing the ERK1/2, JNK and STAT3 signaling pathways. Furthermore, berberine hydrochloride, a primary constituent of DGLHT-E inhibited the expressions of the proliferation markers K16 and K17 in IL-22 stimulated HaCaT cells.

Conclusion: These results suggested that DGLHT-E offers a possible treatment for psoriasis, and that berberine hydrochloride might be a useful component of ointment-based treatments for psoriatic lesions.

Keywords: Abbreviations: IL, interleukin; Anti-proliferation; Berberine hydrochloride; CC motif chemokine ligand 20, CCL20; CXCL10, C-X-C motif chemokine ligand 10; Dang-Gui-Liu-Huang Tang; ELISA, enzyme-linked immunosorbent assay; IL-22; IMQ, imiquimod; K16; Psoriasis.

MeSH terms

  • Administration, Cutaneous
  • Aminoquinolines
  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Humans
  • Imiquimod
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Interleukins
  • Keratinocytes / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Skin / drug effects
  • Th17 Cells / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Aminoquinolines
  • Drugs, Chinese Herbal
  • Interleukins
  • Tumor Necrosis Factor-alpha
  • dong quai
  • Imiquimod
  • interleukin-22