Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with chronic joint inflammation, synovial hyperplasia, and bone erosion, driven by cytokines such as TNF‑α, IL‑6, and COX‑II. These proteins are clinically validated RA targets due to their role in cytokine signaling, chronic inflammation and prostaglandin - mediated pathways. Current therapies, including DMARDs and biologics, are limited by cost, toxicity, and side effects, highlighting the need for safer alternatives. In this study, the leaf extract of Hydnocarpus alpinus is assessed for its anti-inflammatory properties. Soxhlet extraction was carried out in triplicates using ethanol as solvent. 1µL of (5mg/mL) extract was subjected to GC-MS analysis and 25 phytoconstituents were identified. These phytochemicals were subjected to molecular docking of against the inflammatory cytokines, TNF-α (2AZ5), IL-6 (1P9M) and COX-II (5IKR) and compared with the standard drugs, Leflunamide, Naproxen and Resveratrol. Among the tested phytochemicals, friedelan-3-one exhibited the strongest docking affinities with TNF-α (-10.0 kcal/mol), IL-6 (-10.0 kcal/mol), and COX-II (-9.3 kcal/mol). Subsequently, ADME and toxicity predictions confirmed favorable drug-likeness, non-carcinogenicity and high gastrointestinal absorption. Collectively, these findings highlight friedelan-3-one as a promising candidate for targeted RA therapy. Further in vitro and in vivo validation is essential to confirm its therapeutic efficacy and clinical applicability.
