Mechanism‐Based Antiarthritic Activity of Heterophragma adenophyllum : Integrated In Vivo, Gene Expression, and In Silico Targeting of Inflammatory Pathways

Heterophragma adenophyllum (Bignoniaceae) is traditionally used in Southeast Asian medicine to treat several inflammatory disorders, particularly rheumatism and skin conditions. This study aimed to validate its traditional use by evaluating the antiarthritic and anti‐inflammatory potential of the leaf ethanol extract (HAE). Phenolic profiling was performed using high‐performance liquid chromatography (HPLC). Antioxidant activity was assessed via phosphomolybdenum, 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Anti‐inflammatory effects were evaluated in vivo using acute, subacute, and chronic complete Freund’s adjuvant (CFA)–induced arthritis models. Molecular docking and ADMET analyses were also conducted. HPLC analysis revealed seven bioactive constituents mainly phenolic acids. HAE demonstrated moderate antioxidant activity (IC ₅₀ : 79.20, 74.42, and 82.12 μg/mL) in phosphomolybdenum, DPPH, and FRAP, respectively. In vivo , HAE significantly reduced paw oedema; improved body and immune organ indices; and ameliorated biochemical, hematological, radiographic, and histopathological alterations (radiographic score: 4). Gene expression analysis revealed downregulation of proinflammatory cytokines and upregulation of anti‐inflammatory mediators. In silico studies supported these findings and showed strong inhibition of 5‐lipoxygenase, particularly by gallic acid and quercetin. These findings support the traditional use of H. adenophyllum under inflammatory conditions and highlight its potential effect as a source of bioactive compounds for antiarthritic therapies.