A tri-phytochemical formula improves skin barrier function and regulates immune response in atopic dermatitis-like mice

Background: Atopic dermatitis (AD) is associated with IgE- and non-IgE-mediated immune responses, and with skin barrier dysfunction. Ginsenoside Rg1 has been shown to mitigate IgE- mediated allergic rhinitis responses; tetrandrine suppresses abnormal T-cell activation; and icariin improves intestinal barrier functions. Whether the formula comprising ginsenoside Rg1, tetrandrine, and icariin (referred to as GTI) is effective in treating AD remains unexplored.

Purpose: This study aimed to investigate the anti-AD effects and mechanisms of GTI in a mouse model.

Methods: A calcipotriol (MC903)-induced AD-like dermatitis mouse model was used to evaluate the anti-AD effects of GTI. Dermatitis scores and mouse ear thickness were recorded to assess disease severity. Ear tissues, ear-draining lymph nodes, spleens and sera were collected for use in the investigation of the effects and mechanisms of action of GTI.

Results: Topical application of GTI significantly alleviated AD-like dermatitis in mice, as shown by decreased dermatitis scores, ear thickening, epidermal thickness, dermis thickness, and levels of the inflammatory cytokines IL-1β and IL-4 in ear tissues. Unlike the positive dexamethasone, GTI had no significant toxicity in the model mice. Topical GTI lowered serum IgE levels and diminished the accumulation of eosinophils and mast cells in ear tissues of model mice, suggesting that GTI reduces IgE-mediated allergic reactions. GTI significantly decreased the numbers of CD4 + T cells in ear tissues, ear-draining lymph nodes and the spleen, demonstrating a suppressive effect on hyperactive immune responses. The protein levels of ZO-1 and claudin-1, two tight junction proteins, were elevated in mouse ear tissues by GTI, indicating a beneficial effect of this formula on skin barrier function. Also, GTI inhibited the activation of mitogen-activated protein kinases (MAPKs), as demonstrated by the downregulation of protein levels of phospho-p38 (Thr180/182), phospho-ERK (Thr202/Tyr204), and phospho-JNK (Thr183/185) in mouse ear tissues.

Conclusion: This study, for the first time, demonstrated that topical application of GTI alleviates atopic dermatitis symptoms without overt toxicity in a calcipotriol-induced AD mouse model. The anti-AD effects of GTI are associated with suppression of allergic reactions and hyperactive immune responses, improvement of skin barrier function, and inhibition of MAPK activation. These findings suggest that GTI has potential to be developed into a safe and effective drug for treating AD.