Abstract: BACKGROUND: Moxibustion has been demonstrated as an effective therapeutic approach for atopic dermatitis, yet its underlying mechanisms remain to be further elucidated.
OBJECTIVE: To investigate the mechanisms of moxibustion intervention in atopic dermatitis using proteomics technology.
METHODS: Thirty-four Sprague-Dawley rats were randomly divided into three groups: a model group (n=12), a moxibustion group (n=12), and a blank group (n=10). The first two groups were induced to develop an atopic dermatitis model using 2,4-dinitrochlorobenzene. Following successful modeling, the moxibustion group received moxibustion therapy with moxa sticks applied to the Ashi point for 30 minutes per session, maintaining a local temperature of 
(43±1) °C, administered every other day over a 14-day intervention period. The model group and blank control group underwent restraint and fixation procedures of the same duration and intensity. Skin lesion severity after modeling was evaluated using the Eczema Area and Severity Index. Proteomic analysis of rat skin tissue was performed using a data-independent acquisition approach on a high-performance liquid chromatography-tandem mass spectrometry platform. Mass spectrometry data processing, protein identification, differential protein expression analysis, functional annotation, and bioinformatics analyses were conducted using MaxQuant, Perseus software, DAVID (https://david.ncifcrf.gov/), and STRING (https://string-db.org/). A correlation network diagram was constructed using the network visualization tool Cytoscape 3.9.1.
RESULTS AND CONCLUSION: (1) The skin lesion score of atopic dermatitis model rats after moxibustion treatment was significantly lower than that in the model group (P < 0.05), indicating successful establishment of the model. (2) Moxibustion was able to reverse the upregulation of 28 differentially expressed proteins and the downregulation of 40 differentially expressed proteins in the model group. (3) Bioinformatics analysis revealed that the main signaling pathways involved in atopic dermatitis pathogenesis included neuroactive ligand-receptor interaction, viral protein-cytokine and cytokine-receptor interaction, inflammatory mediator regulation of transient receptor potential channels, and neutrophil extracellular trap formation. Among these, the regulation of integrin β3 and β-1,4-galactosyltransferase protein expression was found to be most closely associated with atopic dermatitis pathogenesis. (4) The mechanism by which moxibustion treats atopic dermatitis was found to primarily involve signaling pathways related to infection or immunity, such as herpes simplex virus type 1 infection, olfactory transduction, influenza A, and steroid hormone biosynthesis. The most relevant proteins included nuclear factor κB subunit 1, major histocompatibility complex protein, RT1-Bb, Jak1, and Cdk6. These findings suggest that moxibustion exerts its intervention effect on atopic dermatitis through multi-targets, multi-pathways, and multi-mechanisms. It can reverse the inflammatory response induced by atopic dermatitis while exerting anti-inflammatory and antioxidant effects.

Key words: moxibustion, atopic dermatitis, rats, mechanisms of action, proteomics technology, bioinformatics