Yiyao Ding

Chronic atrophic gastritis (CAG) is a precancerous gastric condition with limited therapeutic interventions, and the mechanisms underlying the benefits of Coptis chinensis Franch. (CCF) remain insufficiently defined. This study employed an integrated computational strategy to clarify the molecular basis of CCF activity against CAG. Network pharmacology was used to identify potential targets of the major CCF constituents berberine, coptisine, and palmatine, followed by molecular docking, machine learning-based IC₅₀ prediction, and molecular dynamics simulations. Fifty-eight overlapping targets between CCF compounds and CAG-related genes were identified, highlighting SRC, STAT3, MAPK1, and NFKB1 as central nodes enriched in inflammatory and immune pathways, including TNF and MAPK signaling. Docking analyses revealed strong interactions between all three compounds and SRC kinase, and machine learning models predicted IC₅₀ values in the low micromolar range (1.38–1.82 μM). Molecular dynamics simulations further suggest that berberine may stabilize the crucial regulatory regions of SRC, specifically the activation loop. It is hypothesized that this stabilization maintains the inactive conformation of the kinase domain and potentially shields Tyr416 from phosphorylation, thus potentially influencing kinase activation. These findings suggest that CCF may modulate key inflammatory and immune pathways implicated in CAG progression, with SRC emerging as a central node for further investigation.

Chrysanthemum (Chrysanthemum morifolium Ramat.) has been recognized as both a food and medicinal substance in China since 2002 and possesses antioxidant, anti-inflammatory, antibacterial, and immunomodulatory activities. Previous studies suggest that Chrysanthemum may alleviate skin lesions resembling atopic dermatitis (AD); however, its underlying mechanisms remain unclear. In this study, we integrated network pharmacology and machine learning to systematically explore the potential mechanisms of Chrysanthemum in AD treatment. Four algorithms—Random Forest (RF), Lasso regression with cross-validation (LassoCV), Elastic Net (EN), and Extreme Gradient Boosting (XGB)—were compared, among which the XGB model achieved the best performance (accuracy = 0.9393). Further analysis identified 15 optimal features, two core targets (PTGS2 and MMP9), and one critical pathway (NF-κB signaling). To experimentally validate these findings, HaCaT keratinocytes were co-stimulated with TNF-α and IFN-γ to establish an in vitro inflammatory model, and co-treatment with three major flavonoids from Chrysanthemum—Acacetin, Diosmetin, and Chryseriol—significantly suppressed cytokine-induced COX-2 overexpression and reduced NF-κB p65 phosphorylation, confirming their inhibitory effects on NF-κB activation. These results were consistent with molecular docking and dynamics simulations, which demonstrated that these flavonoids, along with celecoxib, could stably bind to COX-2, thereby enhancing system stability and reducing residue fluctuations at the binding interface, revealing the molecular basis by which Chrysanthemum alleviates AD and supporting its modernization and therapeutic potential.