Screening Of Rage-Targeted Components From Coptidis For Diabetic Periodontitis

To confirm the disease targets of diabetic periodontitis (DP) and screen the active components of Coptidis for therapeutic action. The common targets of chronic periodontitis and diabetes were obtained by analyzing the data from GEO, GeneCards, and DisGeNET, and the differences in RAGE protein expression were compared using clinical samples from 16 patients (2023-XJKQIEC-YW-0001-002). HEK293 cells with high expression of RAGE were used to construct magnetic nanobait to screen the active components combined with RAGE from Coptidis. The affinity ability between the active components and RAGE was verified by competition binding assay, BIAcore, molecular docking and dynamics simulation. DP cell model was established using LPS and glucose. After treatment with different concentrations of active ingredients, the anti-inflammatory and osteogenic effects were detected by PCR and osteogenic staining. RAGE was identified as the primary pathogenic target in DP. Magnetic nanobait engineered with RAGE overexpression was employed to screen Coptidis, revealing Berberine as the specific RAGE-targeting active component. Competitive binding assays, BIAcore, molecular docking and dynamics simulations confirmed a stable BER-RAGE interaction. DP cellular model was established using 10 g/mL LPS and 20 mM glucose. BER at 0.1 μg/mL demonstrated dual anti-inflammatory (e.g., IL-6↓, TNF-α↓) and osteogenesis-promoting effects (e.g., RUNX2↑, Alizarin Red staining↑), which were mechanistically linked to RAGE modulation. Berberine, an active compound in Coptidis, alleviates DP progression by targeting RAGE to modulate inflammation and osteogenesis.