Abstract
Cimifugin is a bioactive component of Saposhnikovia divaricata, a Chinese herb for treating allergy. Our previous studies demonstrated that cimifugin inhibited allergic inflammation efficiently. This study aims to determine the mechanism of cimifugin on epithelial cells in allergic inflammation. Mice were sensitized and challenged with FITC to establish type 2 atopic dermatitis (AD) model. The initial stage of AD model, in which mice were just sensitized with FITC, was established in vivo and immortalized human epidermal (HaCaT) cells were utilized in vitro. Initiative key cytokines, TSLP and IL‐33, were measured by ELISA, the junctions in ECs were observed by electron microscopy and TJs (CLDN‐1, occludin and CLDND1) were assessed by Western blot, immunohistochemistry and immunofluorescence. The results showed that TSLP and IL‐33 were inhibited significantly by cimifugin in the initial stage of AD model. Simultaneously, cimifugin reduced the separated gap among the epithelial cells and increased the expression of TJs. Similar effects on TSLP/IL‐33 and TJs were obtained in vitro. The effect of cimifugin on TSLP decreased significantly when expression of CLDN1 was interfered with siRNA and this implied cimifugin inhibits initiative cytokines through restoring TJs. Furthermore, cimifugin administered only in the initial stage obviously attenuated the ultimate allergic inflammation, which indicate that impacts of cimifugin in the initial stage on TSLP/IL‐33 and TJs are sufficient for suppressing allergic inflammation. This study not only revealed the mechanisms of cimifugin, but also indicated the possibility of initiative key cytokines and TJs as therapeutic targets.
Highlights
The initial stage of the mice atopic dermatitis (AD) model was established to observe the effect of cimifugin on thymic stromal lymphopoietin (TSLP) and IL-33 in vivo
To confirm the effects of cimifugin on the expression of TSLP and IL33, we examined the effects of cimifugin on the TNF-a-induced production of TSLP and IL-33 in HaCaT cells in vitro
TSLP and IL-33 derived from epithelial cells (ECs) are master switches of allergic inflammation [24,25,26], suggesting that it might be the most important target interfering with the initial stage of allergic diseases [27,28,29]
Summary
Cimifugin is an effective and main component of Saposhnikovia divaricata[1, 2]. The dried roots of S. divaricata, called ‘Fang-Feng’ in Chinese, are well known as a basic traditional Chinese medicine for thousands of years. ‘Fang-Feng’ has anti-inflammatory and antiallergy activities and is widely used for treating allergy, rheumatism, headache and convulsion, especially used as the first choice for allergic dermatitis and skin pruritus. The main components in ‘Fang-Feng’ are cimifugin and prim-o-glucosylcimifugin as types of chromones. Prim-o-glucosylcimifugin is regarded as the quality standard for ‘Fang-Feng’ and would transform into cimifugin in vivo [3], which have pharmacological activities with anti-inflammation and detumescence [4]. We reported cimifugin administered in the sensitization phase of mouse atopic dermatitis (AD) model significantly
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