Background. Atopic dermatitis is a common dermatological disease, and mast cell degranulation is believed to be related with the progression of atopic dermatitis. Mas-related G protein-coupled receptor-X2 (MRGPRX2), and calcium release-activated calcium channel protein 1-2 (ORAI-1, ORAI-2) are involved in mast cell degranulation. Celastrol is an active monomer of Tripterygium wilfordii, and it presents an antiatopic role. Methods. 2,4-Dinitrofluorobenzene (DNFB) and compound 48/80 (C 48/80) were used to establish a slow and acute scratching animal model, respectively. Hematoxylin-eosin and toluidine blue staining was used to investigate tissue injury. Inflammatory factor concentration was measured with ELISA. The expression of MRGPRX2, ORAI-1, and ORAI-2 was detected with immunohistochemistry (IHC) staining. Gene expression profiling and microRNA array were performed to investigate gene differential expression. Results. Celastrol greatly inhibited atopic dermatitis-related tissues injury, mast cell production, histamine release, scratching level, inflammatory factor expression, and activation of MRGPRX2/ORAI axis in the DNFB-induced atopic dermatitis model. The influence of Celastrol on atopic dermatitis was remarkably reversed by overexpression of MRGPRX2. Conclusion. We found that the improvements of atopic dermatitis caused by Celastrol were reversed by treatment with MRGPRX2OE, indicating that Celastrol might affect atopic dermatitis through MRGPRX2. This study might provide a novel thought for the prevention and treatment of atopic dermatitis by regulating MRGPRX2.

Objective: The aim of this research was to analyze the mechanism of tripterine anti-inflammatory and anti-allergic activity in the substance P sensitized mast cells. Methods: Substance P was used to sensitize P815 cells, and Agilent Scanner G2505C gene chip was used to analyze differential gene. The mechanism of tripterine anti-inflammatory and anti-allergic activity was analyzed by qPCR and flow cytometry. Results: Substance P significantly inhibited P815 viability, and significantly increased histamine concentration. Significance analysis showed substance P induced 1711 genes significantly up-regulated with fold change ≥ 2, and 2033 significantly down-regulated. The GO enrichment analysis showed the up-regulated differentially expressed genes (DEGs) significantly enriched in superoxide metabolic process and nucleocytoplasmic transport, and the down-regulated DEGs mainly enriched in phosphoinositide 3-kinase cascade and blood vessel remodeling. The KEGG pathway analysis found the up-regulated DEGs mainly enriched in RNA polymerase and Huntington’s disease, and the down-regulated DEGs mainly enriched in cell adhesion molecules and lysosome. Further research found that tripterine protected substance P- sensitized mast cell by regulating cell adhesion molecules and PI3K/AKT pathway. Conclusions: This study identified some key genes and pathways closely related with sensitized mast cell, and tripterine affected substance P- sensitized cell by adhesion molecules and PI3K/AKT pathway.