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-[alpha]) and interferon-gamma (IFN-[gamma] caused a significant increase in the production of the following chemokines: thymus- and activation- regulated chemokine (TARCJ/CCL17; macrophage-derived chemokine (MDQ/CCL22; regulated on activation, normal T-cell expressed and secreted (RANTESJ/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-[alpha] and IFN-[gamma]-treated control cells. Consistently, JYGCT extract downregulated the mRNA expression of TARC, MDC, RANTES, and IL-8 induced by TNF-[alpha] and IFN- [gamma] in a dose-dependent manner. In addition, TNF-[alpha] and IFN-[gamma] markedly increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and the nuclear translocation of nuclear factor kappa B (NF-[kappa]B) in HaCaT cells. By contrast, TNF-[alpha] and IFN-[gamma]-induced activation of STAT1 and NF-[kappa]B activation was inhibited by JYGCT treatment in a dose-dependent manner.
Our data indicate that JYGCT attenuates TNF-[alpha] and IFN-[gamma]-mediated chemokine production by targeting the STAT1 and NF-[kappa]B signalling in keratinocytes. Our findings suggest that JYGCT has potential as a therapeutic drug candidate for the treatment of inflammatory skin diseases.
Skin immune responses are important aspects of the host defense mechanisms against microorganisms (Pasparakis et al. 2014). Disruption of skin immunity can cause chronic inflammatory skin diseases. T-helper 2 type (Th2) cells, including monocytes, macrophages, eosinophils, and mast cells are crucial cells associated with the development of skin diseases (Meagher et al. 2002; Werfel 2009). Th2 cells are attracted to the skin by inflammatory chemokines, such as regulated on activation, normal T-cell expressed and secreted (RANTES); thymus and activation regulated chemokine (TARC); and macrophage-derived chemokine (MDC). These chemokines interact with the cells via extracellular receptor proteins (Kaburagi et al. 2001; Kakinuma et al. 2002; Shimada et al. 2004). Epidermal keratinocytes play an important role in the control of skin inflammation through their production of inflammatory chemokines (Albanesi 2010). Therefore, chemokines are considered as pivotal mediators in the development of inflammatory skin diseases. Several studies have reported that transcription factors such as signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappa B (NF-[kappa]B) play critical roles in the chemokine production mediated by tumour necrosis factor-alpha (TNF-[alpha]) and/or interferon-gamma (IFN-[gamma]) in keratinocytes (Han et al. 2011; Ju et al. 2009; Kwon et al. 2012).
Accumulating evidence shows that many traditional herbal medicines have anti-inflammatory activities in the skin (Hon et al. 2011; Hughes et al. 2007; Lee do et al. 2009a,2009b). Jakyakgamcho-tang (JYGCT), also called Shaoyao-gancao-tang in Chinese and Shakuyaku-kanzo-to in Japanese, is a traditional herbal medicine comprising two medicinal herbs, Paeonia lactiflora...