Wenshi Jianpi Chushi Tang alleviates pyroptosis and apoptosis in an atopic dermatitis model by synergistically inhibiting the PI3K-Akt/MAPK signaling pathways

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with limited treatment options. Wenshi Jianpi Chushi Tang (WJCT), a traditional Chinese herbal formula commonly used in our hospital, has shown significant efficacy and a low recurrence rate in treating AD. This study systematically investigated the therapeutic mechanisms of WJCT against AD by integrating network pharmacology, bioinformatics, and in vivo and in vitro experiments. Network pharmacology predictions suggested that the core components of WJCT might exert their effects by targeting downstream nodes in signaling pathways such as PI3K-Akt, MAPK, and cell death. In a DNCB-induced mouse model of AD, WJCT treatment significantly alleviated skin inflammatory damage, inhibited the activation of key proteins involved in pyroptosis and apoptosis, and downregulated the phosphorylation levels of the MAPK and PI3K-Akt pathways. In vitro experiments further confirmed that WJCT could inhibit pyroptosis in keratinocytes and both pyroptosis and apoptosis in macrophages. Notably, its inhibitory effects on different MAPK subtypes exhibited cell-type specificity. In conclusion, our findings indicate that WJCT, likely through the synergistic action of its multiple active components, may alleviate AD by suppressing the overactivation of the PI3K-Akt/MAPK signaling pathways and the subsequent aberrant cell death programs. This study provides novel mechanistic insights into the therapeutic application of traditional Chinese herbal formulas for AD.