Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that imposes a significant global health burden, affecting approximately 20% of children and 10% of adults (Asthma and Allergic Diseases, 2025; Guttman-Yassky et al., 2025; Li et al., 2025). The pathogenesis of the disease involves a complex interplay of multiple factors, including genetic susceptibility, impaired epidermal barrier function, and abnormal immune activation (Schuler et al., 2023). Although biological agents such as monoclonal antibodies against cytokines or their receptors and Janus kinase (JAK) inhibitors have significantly improved the treatment landscape for severe AD, topical corticosteroids and calcineurin inhibitors remain the mainstay therapies for mild to moderate cases (Chovatiya and Paller, 2021; Chu et al., 2023). However, long-term use of these drugs may lead to adverse effects, highlighting the urgent need to develop novel treatment strategies capable of achieving long-term disease control.

Traditional Chinese medicine has accumulated centuries of experience in treating dermatitis, with herbs such as Sophora flavescens (Ku Shen) (Wang et al., 2023), Glycyrrhiza uralensis (Gan Cao) (Saeedi et al., 2003), Flos Chamomillae (Yang Gan Ju) (Xu et al., 2024), and Herba Centellae (Ji Xue Cao) (Lee et al., 2020) being widely used. Notable bioactive compounds isolated from these herbs such as matrine (Huang et al., 2025), dipotassium glycyrrhizinate (Lee et al., 2019), α-bisabolol (Li et al., 2022), and asiaticoside (Park, 2021) have demonstrated significant potential as anti-atopic dermatitis (AD) therapeutics. Studies have shown that matrine alleviates AD-related itching and inflammation, as evidenced by reduced epidermal thickening, decreased mast cell infiltration, and downregulated expression of Th2 cytokines, including the interleukin (IL)-4, IL-10, and the pro-inflammatory factors IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) (Wang et al., 2025). Dipotassium glycyrrhizinate exerting corticosteroid-like anti-inflammatory effects without the associated side effects (Lee et al., 2019). α-bisabolol suppresses AD by inhibiting the activation of c-Jun N-terminal kinase (JNK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in mast cells (Li et al., 2022). Asiaticoside significantly promotes wound healing and repairs the skin barrier (Ko et al., 2025; Lee et al., 2020), thereby ameliorating epidermal defects in AD patients and enhancing resistance to external stimuli. Moreover, the widespread use of these compounds in cosmetics indicates their favorable safety profile.

Given the complexity of AD pathogenesis, a combination of active ingredients targeting immune dysregulation, allergic responses, and barrier dysfunction may offer therapeutic advantages over single-component agents. Therefore, this study developed a compound formulation consisting of matrine, dipotassium glycyrrhizinate, a-bisabolol, and asiaticoside (abbreviated as MDBA). To systematically investigate the pharmacological effects and mechanisms of MDBA in AD treatment, we employed a calcipotriol -induced AD-like dermatitis model and a tape stripping–induced physical barrier disruption model. These models allowed a comprehensive evaluation of MDBA's impact on key pathological features of AD, including allergic inflammation, immune dysregulation, and skin barrier function.