Network Pharmacology and Experimental Evaluation of <i>Lonicera japonica</i> Flos in Rheumatoid Arthritis

Lonicera japonica Flos (LJF) possesses antiviral, antioxidant, and anti-inflammatory properties, but its mechanisms against rheumatoid arthritis (RA) are not well understood. This study aims to clarify LJF's molecular mechanisms in treating RA. Active components and targets of LJF and RA were determined using databases such as TCMSP, GeneCards, and OMIM. Protein-protein interaction (PPI) network analysis and pathway enrichment analysis (via KEGG as well as GO databases) were conducted to predict potential targets and pathways. Molecular docking identified potential targets of three specific LJF components. The anti-arthritic effects of LJF were evaluated in vivo using a collagen-induced arthritis (CIA) rat model. Seventeen active LJF components and 126 potential anti-RA targets were identified. Key compounds include quercetin, luteolin, kaempferol, beta-carotene, and beta-sitosterol. Main targets are AKT1, TP53, JUN, TNF, IL6, CASP3, EGFR, RELA, IL1B, and VEGFA. KEGG analysis suggested the involvement of the PI3K-AKT, TNF, and IL-17 pathways. Molecular docking demonstrated that β-sitosterol, quercetin, and luteolin effectively bind to AKT1, IL6, JUN, TNF, and TP53. In vivo studies confirmed that LJF reduces pathological damage and inflammatory markers (TNF-α and IL-6) in a dose-dependent manner, supporting its anti-RA effects via AKT and RELA through PI3K-AKT and NF-κB pathways. This research identified the PI3K-AKT and NF-κB signaling pathways as key targets of LJF, highlighting their roles in its anti-RA effects. These findings point to the possibility of advancing research and clinical use of LJF in RA treatment.