Traditional herbal formula Jakyakgamcho-tang (Paeonia lactiflora and Glycyrrhiza uralensis) impairs inflammatory chemokine production by inhibiting activation of STAT1 and NF-κB in HaCaT cells

Phytomedicine. 2015 Feb 15;22(2):326-32. doi: 10.1016/j.phymed.2014.12.002. Epub 2015 Jan 5.

Abstract

A traditional herbal formula Jakyakgamcho-tang (JYGCT; Paeonia lactiflora and Glycyrrhiza uralensis) has been used for treatment of backache, muscle pain, acute abdominal pain, neuralgia, bronchial asthma, and painful peripheral neuropathy in Oriental medicine. We report on our experiments using the HaCaT human keratinocyte cell line showing that a traditional herbal formula JYGCT has inhibitory effects on inflammatory responses in skin. Stimulation with tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) caused a significant increase in the production of the following chemokines: thymus- and activation-regulated chemokine (TARC)/CCL17; macrophage-derived chemokine (MDC)/CCL22; regulated on activation, normal T-cell expressed and secreted (RANTES)/CCL5; and interleukin-8 (IL-8) in HaCaT cells. By contrast, treatment with JYGCT extract significantly reduced the production of TARC, MDC, RANTES, and IL-8, but caused no cytotoxicity, compared with TNF-α and IFN-γ-treated control cells. Consistently, JYGCT extract downregulated the mRNA expression of TARC, MDC, RANTES, and IL-8 induced by TNF-α and IFN-γ in a dose-dependent manner. In addition, TNF-α and IFN-γ markedly increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and the nuclear translocation of nuclear factor kappa B (NF-κB) in HaCaT cells. By contrast, TNF-α and IFN-γ-induced activation of STAT1 and NF-κB activation was inhibited by JYGCT treatment in a dose-dependent manner. Our data indicate that JYGCT attenuates TNF-α and IFN-γ-mediated chemokine production by targeting the STAT1 and NF-κB signalling in keratinocytes. Our findings suggest that JYGCT has potential as a therapeutic drug candidate for the treatment of inflammatory skin diseases.

Keywords: Chemokine; Glycyrrhiza uralensis; Inflammation; Jakyakgamcho-tang; Paeonia lactiflora; STAT1/NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chemokine CCL17 / metabolism
  • Chemokine CCL22 / metabolism
  • Chemokine CCL5 / metabolism
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology*
  • Glycyrrhiza uralensis / chemistry
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-8 / metabolism
  • Keratinocytes / drug effects*
  • NF-kappa B / metabolism*
  • Paeonia / chemistry
  • STAT1 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • CCL17 protein, human
  • CCL22 protein, human
  • CCL5 protein, human
  • CXCL8 protein, human
  • Chemokine CCL17
  • Chemokine CCL22
  • Chemokine CCL5
  • Cytokines
  • Drugs, Chinese Herbal
  • Interleukin-8
  • NF-kappa B
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Tumor Necrosis Factor-alpha
  • jackyakamcho-tang
  • Interferon-gamma