reproducible-computational-workflow-for-drug-discovery-to-standardize

Reproducible Computational Workflow for Drug Discovery to Standardize Network Pharmacology and Molecular Docking Analyses

Network pharmacology and molecular docking are widely applied in drug discovery, yet fragmented workflows and inconsistent operations frequently undermine ...

Beijing University of Chinese Medicine

Atopic dermatitis (ad) is a chronic inflammatory skin disease, with recent studies indicating that immune cells, such as monocytes and inflammatory cytokines, play a crucial role. By retrieving datasets from public databases and analysing immune cell infiltration in lesional skin using CIBERSORT, we found that monocytes and M2 macrophages were significantly upregulated in atopic dermatitis. Differentially expressed gene (DEG) functional enrichment analysis revealed that cytokine-cytokine receptor interaction was the most significantly enriched pathway. Further analysis of cytokines and their receptors, along with their correlation with infiltrating immune cells, identified IL36G-expressing monocytes as a key target in atopic dermatitis. We compared immune cell infiltration and cytokine-related targets in similar inflammatory skin diseases, such as psoriasis and urticaria, to evaluate similarities and differences among these three skin conditions. The analysis revealed that IL36G-expressing monocytes were also highly expressed in psoriasis but did not play a pivotal role in urticaria. Finally, we used molecular docking to predict and validate drugs targeting IL36G. Our study highlights IL36G-expressing monocytes as a common key target in atopic dermatitis and psoriasis, offering novel insights and therapeutic strategies for these related diseases.

Monocytes Expressing IL-36G Play a Crucial Role in Atopic Dermatitis.

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.

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

Lanatoside C (LanaC), a cardiac glycoside, has been reported to possess therapeutic potential in acute intestinal inflammation; however, its in vivo effects on ulcerative colitis (UC) remain incompletely understood. In this study, we demonstrated that LanaC effectively attenuates DSS-induced colitis in mice by reducing inflammation, mitigating epithelial damage, and preserving barrier integrity. Mechanistically, LanaC treatment was associated with reduced macrophage infiltration in the colon and spleen, suppression of pro-inflammatory M1 macrophage markers, and enhancement of M2-associated markers. In vitro, LanaC inhibited LPS-induced M1 polarization and pro-inflammatory cytokine production in BMDMs, while promoting IL-4-driven M2 polarization and anti-inflammatory cytokine expression. These effects were accompanied by attenuation of STAT1/STAT3 signaling and enhancement of STAT6 activation, suggesting a selective reprogramming of macrophage responses. Collectively, these findings reveal that LanaC alleviates DSS-induced colitis, at least in part, through regulating macrophage infiltration and repolarization supporting its potential as a macrophage-targeted therapeutic candidate in UC.

Article	Year
Monocytes Expressing IL-36G Play a Crucial Role in Atopic Dermatitis. Journal of cellular and molecular medicine\| PubMed ID: 40159643	2025
Combining AlphaFold-based AI docking with omics technologies preliminarily unveils the mechanism of Guominkang in treating allergic rhinitis. Scientific reports\| PubMed ID: 41136520	2025
Lanatoside C ameliorates DSS-induced colitis with improved intestinal barrier integrity and reduced M1 macrophage polarization. Scientific reports\| PubMed ID: 41606129	2026

Longmei Yu

Biography

JoVE Journal Publications

Other Publications