Combining AlphaFold-based AI docking with omics technologies preliminarily unveils the mechanism of Guominkang in...

Allergic rhinitis (AR) is a common immune-mediated chronic inflammatory disease with a complex pathogenesis involving multiple responses of the immune system and epigenetic changes. In recent years, DNA methylation, a key epigenetic mechanism, has been shown to play an important role in the onset and development of AR. GuoMinKang (GMK) have been used in the treatment of AR through their multi-component properties. However, its specific epigenetic regulatory mechanisms have not been fully investigated. The aim of this study was to explore the epigenetic regulatory mechanisms of the traditional Chinese medicine compound GMK in the treatment of AR. By analysing DNA methylation and transcriptome data from AR patients, we identified differentially methylated regions (DMRs) and differentially expressed genes (DEGs) associated with AR. Through network pharmacology analysis, we screened the active components of GMK and their potential target genes, particularly those related to DNA methyltransferases (DNMTs). An AR mouse model was established to observe the behavioural and pathological changes of the nasal mucosa of mice after drug administration; the expression of IgE cytokines was detected by ELISA, and the expression of nasal mucosa genes was verified by qPCR. Total IgE (tIgE) levels were significantly reduced in AR patients after GMK treatment, suggesting a possible role in immunomodulation. Our analysis revealed that GMK was able to restore aberrant methylation patterns in AR patients by modulating specific DNA methylation regions. Through differential methylation analysis, we identified 10 genes whose methylation levels were significantly restored to normal after GMK treatment and which already showed significant differential expression in AR patients, particularly in immune regulation and epithelial cell function. These genes include LERP, NFIA, etc., suggesting that they may play a key role in the onset and development of AR. Further through target prediction and network pharmacological analyses, we confirmed that the active ingredients of GMK (e.g., quercetin, coumarin, and geranylgeranyl) may exert their epigenetic regulatory functions by targeting the protein activity of DNMTs. In vivo experiments showed that GMK reduced the number of nose scratching and sneezing in mice, glandular hyperplasia in the nasal mucosa was alleviated, with a reduction in the number and volume of glands, and serum tIgE levels were reduced. The increase in LERP expression in the AR model was reduced after treatment with GMK, and the change in NFIA expression was not significant. It suggests that GMK may regulate LERP activity through DNMTs to alleviate allergic symptoms. This study reveals the potential therapeutic mechanism of the traditional Chinese medicine compound GMK in regulating AR through epigenetic mechanisms. These findings provide a theoretical basis and molecular foundation for the clinical application of GMK in AR and open up new research directions.