Unveiling the anti-hyperuricemic potential of Aquilaria malaccensis leaf’s methanolic extract: A multi-approach phytospectral, in silico, in vivo, radiographic investigation in rats

• Hypoxanthine and potassium oxonate intraperitoneally for 7 days, induced hyperuricemia in rats. • Methanolic extract of Aquilaria malaccensis (AMME) phytoconstituents exhibited strong binding affinity with the xanthine oxidase enzyme (PDB ID: 1FIQ ). • AMME demonstrated in vitro membrane-stabilizing activity, indicating potential anti-inflammatory effects. • AMME significantly reduced hypoxanthine and potassium oxonate-induced elevation of serum uric acid levels in rats. • AMME treatment restored altered renal tissue architecture and improved joint morphology in hyperuricemic rats. Hyperuricemia, characterized by elevated serum uric acid (UA), is a major risk factor for gout, renal injury, and osteoarthritic complications. Current urate-lowering agents can cause adverse effects. Aquilaria malaccensis (沉香, Chénxiāng, AM), traditionally used in Traditional Chinese Medicine (TCM) to regulate Qi, relieve pain, and support renal function, contains flavonoid-rich constituents that may offer metabolic and anti-inflammatory benefits. This study investigates the anti-hyperuricemic potential of A. malaccensis methanolic extract (AMME) through phytochemical, in vitro, in vivo , and in silico approaches. Methanolic leaf extract of authenticated AM was subjected to phytochemical screening, TLC, UV–Vis, and FT-IR characterization. Molecular docking was performed with xanthine oxidase (XO, PDB: 1FIQ). Hyperuricemia was induced in rats using potassium oxonate and hypoxanthine, followed by treatment with AMME. Serum uric acid (UA) and C-reactive protein (CRP) levels were quantified, while renal histopathological analysis, knee joint radiography, and an in vitro membrane-stabilization assay were performed to evaluate protective and anti-inflammatory effects. Flavonoids such as acacetin, luteolin derivatives, and 5-hydroxy-7,4′-dimethoxyflavone were identified (TLC Rf = 0.84; UV–Vis λ_max = 210, 258 nm). Docking showed favourable interactions of these compounds with XO. AMME exhibited notable membrane stabilization (85.8% inhibition at 800 µg/mL; IC₅₀ = 143.56 µg/mL). In vivo, AMME (500–1000 mg/kg) significantly reduced serum UA and CRP levels and ameliorated renal and articular alterations. Flavonoid-rich AMME exhibited anti-hyperuricemic, anti-inflammatory, and renoprotective activities, supporting the traditional use of AM. Further studies on active-compound isolation, mechanistic validation, and pharmacokinetics are warranted.