A tri-compound formula comprising Ginsenoside Rg1, tetrandrine and icariin alleviates atopic dermatitis symptoms in a mouse model

Atopic dermatitis (AD) is characterized by both IgE- and non-IgE-mediated immune responses, as well as skin barrier dysfunction. Ginsenoside Rg1, tetrandrine, and icariin each exhibit distinct properties that may contribute to the management of AD. Ginsenoside Rg1 has demonstrated efficacy in mitigating IgE-mediated allergic rhinitis, while tetrandrine is known to suppress abnormal T-cell activation. Icariin has been shown to improve intestinal barrier function, which is crucial in conditions like AD. However, the potential effectiveness of the combined formula of these compounds, referred to as GTI, in treating AD remains unexplored. This study aimed to investigate the anti-AD effects and mechanisms of GTI in a mouse model. 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. Topical application of GTI significantly alleviated AD-like dermatitis in mice, as evidenced by decreased dermatitis scores, reduced ear thickening, and diminished epidermal and dermal thickness, along with lower 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 mitigates IgE-mediated allergic reactions. GTI significantly decreased the numbers of CD4 + T cells in ear tissues, ear-draining lymph nodes and the spleen, demonstrating its suppressive effect on hyperactive immune responses. The protein levels of ZO-1 and claudin-1, two tight junction proteins, were elevated in the ear tissues of mice treated with GTI, indicating a beneficial effect of this formula on skin barrier function. Additionally, GTI inhibited the activation of mitogen-activated protein kinases (MAPKs), as indicated by the downregulation of phospho-p38 (Thr180/182), phospho-ERK (Thr202/Tyr204), and phospho-JNK (Thr183/185) protein levels in mouse ear tissues. This study, for the first time, demonstrated that the topical application of GTI alleviates symptoms of AD without overt toxicity in a calcipotriol-induced AD mouse model. The anti-AD effects of GTI are associated with the suppression of allergic reactions, reduction of hyperactive immune responses, improvement of skin barrier function, and inhibition of MAPK activation. These findings suggest that GTI has the potential to be developed into a safe and effective treatment for AD.