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

Atraditional herbal formula Jakyakgamcho-tang (JYGCT; Paeonia lactiflora and GlycytTliiza nralensis) 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 INF-a) and interferon-gamma (IFN-y) 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 TINF-ce and IFN-y-treated control cells. Consistently, JYGCT extract downregulated the mRNA expression of TARC, MDC, RANTES, and IL-8 induced by INF-a and IFN-y in a dose-dependent manner. In addition, TNF-a and IFN-y markedly increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and the nuclear translocation of nuclear factor kappa B (NF-K B) in HaCaT cells. By contrast, TNF-a and IFN-y-induced activation of STAT1 and NF-KB activation was inhibited by JYGCT treatment in a dose-dependent manner. Our data indicate that JYGCT attenuates TNF-a and IFN-y-mediated chemokine production by targeting the STAT1 and NF-KB signalling in keratinocytes. Our findings suggest thatJYGCT has potential as a therapeutic drug candidate for the treatment of inflammatory skin diseases. (C) 2015 Elsevier GmbH. All rights reserved