Essential oil from Chrysanthemum boreale flowers modulates SNARE protein-linked mast cell response and skin barrier proteins and ameliorates atopic dermatitis-like lesions in mice

Abstract

Chrysanthemum boreale (CB) has diverse properties including anti-inflammatory and anti-tumor effects. Atopic dermatitis (AD) is a chronic inflammatory skin disease, and many attempts have been made to overcome it. However, the effects of CB flower essential oil (CBFEO) on AD has not been determined. This study investigated the potential effect of CBFEO on AD-related pathological events using in vitro and in vivo tests and predicted its related mechanism. CBFEO effects were tested using tumor necrosis factor-alpha (TNF-alpha)-treated human keratinocytes (HaCaT cells) and IgE-sensitized RBL-2H3 mast cells in vitro and 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mice in vivo. Proteins were analyzed by immunoprecipitation, immunoblotting, or immunohistochemistry. beta-Hexosaminidase and histamine levels were measured by ELISA. Skin lesions were assessed using SCORAD scores. CBFEO reduced histamine and beta-hexosaminidase released from mast cells. It also attenuated SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) protein VAMP8 expression and binding of VAMP8 to SNAP23 and syntaxin 4 to SNAP23 in mast cells. In addition, CBFEO inhibited the down-regulation of skin barrier-related proteins (filaggrin and loricrin) by TNF-alpha in keratinocytes. Application of CBFEO to AD-like skin lesions in DNCB mouse model of AD reduced the severity of dermatitis lesions and the expression levels of filaggrin and loricrin in lesioned skin tissues. These findings suggest that CBFEO inhibits AD-like skin lesions in mice probably by interfering with the SNARE protein-associated mast cell degranulation and by enhancing the expression of skin barrier-related proteins. Therefore, CBFEO may be a potential functional material for AD treatment.