Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via Jak3/Stat3 signaling pathway

Int Immunopharmacol. 2016 Mar:32:32-38. doi: 10.1016/j.intimp.2015.12.035. Epub 2016 Jan 16.

Abstract

The flavonoid astilbin is the major active component extracted from the rhizome of Smilax glabra, which has been widely used in China to treat inflammatory and autoimmune diseases, Psoriasis is a common chronic inflammatory disease in which T helper 17 (Th17) cells play an important role, provoking inflammation. We employed an imiquimod (IMQ)-induced psoriasis-like mouse model to investigate the effect of astilbin in inflammation. Mice were administered 25 to 50mg/kg astilbin. Inflammation of psoriasis-like lesions was assessed by histology, circulating levels of T cells were assessed by flow cytometry and cytokines by bead-based immunoassay. Jak/Stat3 in isolated T cells was assessed by Western blotting and RORγt expression was assessed by RT-PCR. Administration of astilbin ameliorated IMQ-induced keratinocyte proliferation, infiltration of CD3+ cells to psoriatic lesions and ameliorated elevations in circulating CD4+ and CD8+ T cells and inflammatory cytokines (IL-17A, TNF-α, IL-6, IFN-γ and IL-2). In vitro, astilbin inhibited Th17 cell differentiation and IL-17 secretion of isolated T cells, and inhibited Jak/Stat3 signaling in Th17 cells, while up-regulating Stat3 inhibitor SCOSE3 expression in psoriatic lesions. Thus, astilbin likely alleviates psoriasis-like skin lesions by inhibiting Th17 related inflammation. Astilbin represents as an interesting candidate drug for immunoregulation of psoriasis.

Keywords: Astilbin; IL-17; Imiquimod; Inflammation; Psoriasis; Th17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Flavonols / pharmacology*
  • Flavonols / therapeutic use*
  • Imiquimod
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use*
  • Interleukin-17 / immunology
  • Janus Kinase 3 / immunology
  • Keratinocytes / drug effects
  • Keratinocytes / immunology
  • Keratinocytes / physiology
  • Male
  • Mice, Inbred BALB C
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / pathology
  • STAT3 Transcription Factor / immunology
  • Signal Transduction / drug effects
  • Skin / drug effects
  • Skin / immunology
  • Skin / pathology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Th17 Cells / physiology

Substances

  • Aminoquinolines
  • Anti-Inflammatory Agents
  • Flavonols
  • Immunologic Factors
  • Interleukin-17
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • astilbin
  • Jak3 protein, mouse
  • Janus Kinase 3
  • Imiquimod